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US Pharmacopeia plans mechanism to monitor quality of Indian medicines

http://www.livemint.com/Companies/mlQXwb7FpJNcjfZOtZUyJN/US-Pharmacopeia-plansmechanism-to-monitor-quality-of-Indian.html
US Pharmacopeia says move to help policymakers make a strong case for investment in quality
Hyderabad: US Pharmacopeia (USP), the non-profit public standards-setting organization for medicines,
dietary supplements and foods sold in the US and consumed worldwide, said on Monday that it was
planning to launch a new system to generate data about the quality of medicines in India to help
policymakers make a strong case for investment in quality. As of now, USP does not have much data on
India, chief executive officer Ronald T. Piervincenzi said. At the moment, we are going through the
process of identifying ways to do more original research and help to use that as a way to advocate the
value of quality, Piervincenzi said. Piervincenzi was in India to celebrate the 10th anniversary of
USPs Hyderabad facility.USP opened its first office and collaborative laboratory facility outside of the
US near Hyderabad in 2005 to help its work of developing and updating quality standards for medicines.
In these years, the Hyderabad facility grew from just seven employees to 170 people, making it the
largest USP facility in the world, serving drug manufacturers in India, Africa and South-East Asia to
help ensure quality along with supporting a regulatory framework for compliance with standards. Substandard and counterfeit drugs are a major cause of concern in most developing countries with a weak
regulatory enforcement.USP works closely with drug regulators, enforcement agencies and industry in
the developing world including India through training and capacity building to combat sub-standard
drugs with funding by USAID.
It also supports drug regulators in the developing world with quality assurance (QA) and quality control
(QC) systems to ensure that quality medicines reach patients.In a world where substandard and
counterfeit medicines are prevalent, the loss of trust to the whole health system creates a series of
follow-on problems. We believe that quality is extremely important and to be our first priority,
Piervincenzi said. Piervincenzi said USP has helped Ghana to reduce the prevalence of sub-standard
drugs from 80% to under 10% in 10 years, and was trying to replicate the model in other
countries.Under-10% isnt the final goal, but the ability to change from that situation to substantially
better was proved achievable, Piervincenzi said. Piervincenzi said USP is also working on a $200
million project over the next four years to update drug monographs, which specify the ingredients a drug
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may contain and the directions for its use.We have already made a public pledge to take the full 200
years of cumulative knowledge of USP, which involves 9,000-10,000 pages of standards, and thousands
of associated physical reference material and have them up to date by 2021, Piervincenzi said.
Threat of diseases as pollution levels rise
Chukwuma Muanya
11 December 2016
http://guardian.ng/saturday-magazine/cover/threat-of-diseases-as-pollution-levels-rise/
Four major cities in Nigeria, Onitsha, Kaduna, Aba and Umuahia, were recently listed by the World
Health Organisation (WHO) as some of the most polluted places in the world. Onitsha, which plays host
to the biggest market in West Africa, Onitsha Main Market, was named as the most polluted city in the
world. Although, some Nigerian experts disagree that Onitsha is the most polluted city in the world, they
however predicted epidemic of cancers, incidence of heart attacks and other cardiovascular diseases, and
respiratory diseases because of rising pollution levels in the country. The WHO report had listed the
Nigerian cities because of high level of smog, rubbish and polluted water. Last year, the World Bank
reported that 94 per cent of the population in Nigeria is exposed to air pollution levels that exceed WHO
guidelines (compared to 72 per cent on average in sub-Saharan Africa in general) and air pollution
damage costs about one per cent post of Gross National Income.A medical practitioner and Director at
Medical Art Centre Maryland Ikeja, Lagos, Prof. Oladapo A. Ashiru, disagrees with WHO that Onitsha
is the most polluted city in the world. The Professor of Anatomy and Consultant Reproductive
Endocrinologist told The Guardian: I do not agree that Onitsha is the most polluted city in the world
because Onitsha under the governance of Mr. Peter Obi three years ago, underwent a transformation
where both road construction and thorough environmental sanitation was observed, making Onitsha
clean again.A consultant pharmaceutical chemist at University of Lagos, Dr Chimezie Anyakora, who
has probed and documented the environmental impact of crude oil based pollutants, polynuclear
aromatic hydrocarbons (PAHs) also disagrees that Onitsha is the most polluted city in the world. PAHs
are a group of organic contaminants that form from the incomplete combustion of hydrocarbons, such as
crude oil, petroleum products, coal and gasoline. PAHs are an environmental concern because they are
toxic to aquatic life and because several are suspected human carcinogens. The result of the probe was
compiled in a book titled Environmental Impact of Polynuclear Aromatic Hydrocarbons.Anyakora
told The Guardian: I lived in Onitsha for many years but I am not sure of its present pollution status,
but like most African cities with intense economic activities I expect a high level of pollution in Onitsha.
But not only Onitsha but various other cities across Nigeria.What are the health implications of
pollution? According to the WHO, about three million deaths a year are linked to exposure to outdoor
air pollution. Indoor air pollution can be just as deadly. In 2012, an estimated 6.5 million deaths (11.6
per cent of all global deaths) were associated with indoor and outdoor air pollution together. Major
sources of air pollution include, inefficient modes of transport, household fuel and waste burning, coalfired power plants, and industrial activities. However, not all air pollution originates from human
activity. For example, air quality can also be influenced by dust storms, particularly in regions close to
deserts. Ashiru, who is also an adjunct professor at the University of Illinois, United States (U.S.)
explained: Environmental pollution consist of five major sources, air, water, land, noise and light. Its
implication will include; airinhaling environmental toxins such as carbondioxide (CO2) and so on can
lead to medical conditions such as lung cancer.Water water pollution usually come from industrial
wastes entering major sources of water example lakes and rivers. Medical condition associated with
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water pollution can range from simple diarrhoea to a more deadly illness like Sepsis. There is also a very
serious one from insects, fleas, tics, mosquitoes-transmitting diseases such as malaria and lyme, which is
even more dangerous.
Soil The major concern in soil pollution is Chlorofluorocarbons (CFC) released from our refrigerator,
air conditions, deodorants and insect repellents; all leading to damage in our ozone layer and eventually
global warming. Noise pollution from aircrafts, trucks and high intensity sonar effects and light
pollution from over illumination and astronomical interference are very harmful to our environment with
long term side effects like deafness and poor eyesight.Anyakora said studies had shown that more
Nigerians are at a greater risk of developing different types of cancer due to exposure to crude oil
pollutants. He predicts that if nothing were done urgently to address the issue, there would be increased
cases of cancer in Nigeria by 2025, especially in the oil-rich Niger Delta. According to the studies led by
Anyakora, more than 25 per cent of Nigerians are at an increased risk of developing cancer due to
exposure to toxic chemicals from crude oil pollution, PAHs. They also suggested that PAHs could be
genotoxic; that is, the damage caused can be inherited. Previous studies had also indicated that PAHs
caused a decrease in sperm count and fertility in crude oil-polluted environment of the Niger Delta.
However, besides the people of the Niger Delta, the studies indicate that other Nigerians, even children,
are exposed to high level of crude oil pollution and are at the risk of developing cancer. One of the two
studies is the first Nigerian research linking PAHs to cancer.In the next 10 years, I see a big problem
here. With rising cases of oil spills in the Niger Delta region and our overdependence on petroleum
products, we are going to see so many cases of cancer, Anyakora told The Guardian.
Anyakora is now chief of party of United States Pharmacopeia (USP) in Nigeria. USP is an affiliate of
the United States Agency for International Development (USAID).He said health consequences of
pollution depends on the type of pollution but pollution has dire consequences on human health and the
tragedy is that this is highly underestimated. The pharmaceutical chemist said another rising concern is
pharmaceutical waste. Anyakora explained: These are caused by improper disposal of unused and
expired medicine. Even in the US this is becoming a rising concern. US Environmental Protection
Agency (EPA) classified pharmaceutical wastes among the top five emerging contaminants affecting
human and ecological health. This has led to a renewed interest in this new field, which is a meeting
point of pharmaceutical analysis, toxicology and environmental science. The environmental
concentrations of these compounds are generally of magnitude below therapeutic doses, but such low
level exposures could nonetheless pose risks.According to a study titled Environmental Health Effects
of Exposure to Air Pollution in Industrialized Areas by Otti, V.I. and Ogbuagu F.U from the
Department of Civil Engineering, Federal Polytechnic, Oko, Anambra State, The respiratory system is
the primary indicator of air pollution effects in humans, as carbon dioxide diffuses through the capillary
wall into the alveolus, while oxygen diffuses out of the alveolus into the blood cell.The study published
in journal Civil and Environmental Research noted: The difference in partial pressure of each of the gas
causes it to move from the higher to lower respiratory track, causing a great cardio-respiratory ailment
amongst the heavy smokers and people living in industrial areas. Air pollution, example, among former
workers of Nkalagu cement industry in Enugu State aggravate some chronic respiratory disease like
Bronchial Asthma.Carbon monoxide, an air pollutant reacts with haemoglobin in the blood to form
carboxylhaemoglobin (COHb), which effectively deprives the blood of oxygen. The excess COHb can
cause a severe heart disease, which can limit the patient from performing certain exercise. Ferris (1978)
stated that a concentration of 20ppm of carbon monoxide for eight hours will result in a carboxyl
haemoglobin level of about 2.8 per cent and the average concentration of carbon monoxide inhaled in
3

cigarette smoke is 200 to 400ppm. This shows that in some industrialized cities, their sensitive
population is those with heart and circulating ailments, chronic pulmonary disease and developing
fetuses.The effects of hazardous air pollutants in the lungs of most industrial workers are generally
higher than in the ambient air and this is obvious because the low level of toxic air is found in ambient
air Nitrogen dioxide (NO2) also has effect that can result in cough and irritation of respiratory tract.
According to Hardoy, (2001), at 5ppm, Nitrogen dioxide has a pungent odour and the concentration in
tobacco smoke is high, can slightly increase the respiratory illness and decrease in pulmonary function
associated with concentration of Nitrogen oxide.
Solutions
Ashiru recommended: Solutions will include public awareness and information about how these toxins
are produced, their effects to our environment and how they (the public) can help reduce it production to
the minimal.
Simple things we can do to reduce pollution includes, walking instead of driving when it can be
avoided, driving hybrid cars, stop smoking, never use open fire to dispose of wastes, observe 3Rs of
solid waste management that is Reduce, Reuse and Recycle, buy local foods and goods that are eco
friendly, plant more trees, do not litter, always consider environmental impact of you businesses.
Government can set up environmental protection agencies to regulate greenhouse emissions. They can
build incinerators at approved location, which are not close to habitable places. They can build recycle
plants where waste can be converted to energy. The Government can setup alternative, efficient and
reliable transport system leading to less environmental pollution.
They can setup anti pollution policies such as carbon taxes, pollution permits and subsidy policies on
alternative energy. Sensitise the public on hazards associated with environmental pollution by
organising outreach groups that will deliver seminars and lectures to the people. They should encourage
proper waste disposal. Donations in forms of recycle bins; protection gloves and so on should be made.
These organisations can help fight deforestation and work closely with the environmental impact
assessment agencies (EIA) by providing intelligence.
Anyakora said the solution to this is simple. He explained: All relevant regulators should step up. It is a
public health issue. Citizens need to be educated on the health implication of incessant contamination of
the environment. The infectious disease burden in Nigeria is already high and the non-infectious disease
burden is also rising at an alarming rate and environmental pollution contributes significantly to that.
On what residents should do to protect themselves from these consequences, Anyakora said: It is a
problem that has universal scope. Pollution at one point can have impact on people living very far away.
Once the ground water gets polluted, there is no boundary. Everyone is exposed. Across the world
governments are bringing tighter regulation to protect public health. It is the governments duty. It
should not be a voluntary decision of the residents.
What must the government do? The pharmaceutical chemist said: The government should step up. We
are losing a lot of money on health and lost man-hours due to disease burden. Anyakora further stated:
We should put pressure on each other to safeguard the environment. It is everyones business. If your
neighbor is polluting the environment, he is harming you. The harm may be more dangerous than the
man stabbing you. So speak up, do something, put pressure on government to do something, otherwise
4

sooner or later you or your loved one will be tackling one ill health or the other as a result of that
negligence. It is quite painful to see many people who can contribute significantly to nation building
with their energy and youth go down with some ill health that is avoidable. We need to minimize this to
the best of our ability.

Solix Algredients Gains ConsumerLab.com Quality Certification and Continues its USA Market
Penetration with a New 10% Solasta Astaxanthin Product
http://www.prnewswire.com/news-releases/solix-algredients-gains-consumerlabcom-qualitycertification-and-continues-its-usa-market-penetration-with-a-new-10-solasta-astaxanthin-product300376712.html
FORT COLLINS, Colo., Dec. 13, 2016 /PRNewswire/ -- Solix Algredients, Inc. announces that
Solasta Astaxanthin has received the "Approved Quality" seal certification from
ConsumerLab.com.Solasta is a natural astaxanthin extract produced from Haematococcus pluvialis
(microalgae). It is non-GMO, vegetarian, extracted in the USA, and complies with the stringent United
States Pharmacopeia (USP) specification.The ConsumerLab.com seal is the latest confirmation of Solix
Algredients' ongoing efforts to provide the industry with high-quality, natural algal ingredients. Earlier
this year, Solix was certified by UL Registrar as meeting the Natural Product Association's (NPA)
requirements for compliance with the U.S. Food and Drug Administration's (FDA) Good Manufacturing
Practices (GMPs) for dietary supplements. Solix Algredients also extended its Solasta Astaxanthin
product range with a new product tailored for easier handling and processing efficiency. The new 10%
natural astaxanthin oleoresin product, called Solasta 110, provides improved flowability due to its
lower viscosity."Our new Solasta 110 extends our range of astaxanthin products providing greater
operational flexibility and cost savings to the makers of dietary supplements, nutritional beverages and
personal care products," said Charlie Bowman, Chief Commercial Officer."USP quality, supply chain
speed and flexibility, combined with our capability to formulate Solasta in a variety of carrier oils and
other ingredients, enable our customers to differentiate and increase their sales," explained Bowman.
About Solix Algredients, Inc.
Solix Algredients is a B2B supplier of algae-based, natural ingredients that benefit health-conscious
consumers. The company is a recognized leader in algal cultivation and has demonstrated its technology
at scale. The USA-based company is applying its algae supply chain experience and expertise to bring
Solasta Astaxanthin, Solmega DHA omega-3 and other natural algal ingredients to market. Solix
Algredients is headquartered in Fort Collins, Colorado, where it has an array of algae-specific technical,
R&D and analytical resources.

IPC adds 19 New Impurities Standards for related substance analysis

Nandita Vijay, Bengaluru
Saturday, December 31, 2016
http://www.pharmabiz.com/NewsDetails.aspx?aid=99554&sid=1
Indian Pharmacopoeia Commission (IPC) Ghaziabad has added 19 New Impurities Standards to its list.
Now a total of 72 Impurities and 517 IPRS (Indian Pharmacopoeia Reference Substances) are available
at IPC for stakeholders. The move is to strengthen its availability of impurity standards and reference
substances. The new list of impurity standards covered Sodium propyl paraben impurity A, Noscapine
hydrochloride impurity A, 2-methyl-2-nitropropane-1,3-diol (Bronopol impurity), 2-Nitroethanol,
Mesalazine Impurity L, Sodium Bromide, 3-Pyridyl acetic acid hydrochloride (Risedronate sodium
impurity), Fexofenadine Hydrochloride Impurity A, Tris (hydroxymethyl) nitromethane (Bronopol
Impurity), Clotrimazole Impurity E, Mesalazine Impurity K, Mesalazine Impurity M, 4-Chlorobenzoic
Acid (Indomethacin Impurity), Cyclizine Impurity B, Oxalic Acid Dihydrate, Levodopa Impurity B,
Iminodibenzyl, 2-methylimidazole (Ondansetron hydrochloride Impurity), 1-vinylpyrrolidin-2-one
(Povidone Impurity). In the case of Indian Pharmacopoeia Reference Substances total 517 are available
with the IP Commission.

According to Dr. P. L. Sahu, principal scientific officer and head-R&D, Indian Pharmacopoeia
Commission, impurity standards are very essential for related substance analysis. Further, it is also
important for ensuring the product quality. Impurity standards are used to perform the system suitability,
qualitative and quantitative parameters for compliance to Indian Pharmacopoeia monograph. The
Commission has created a set of standards for drugs in the country. Its basic function is to update
regularly the standards of drugs commonly required for treatment of diseases prevailing in this region. It
publishes official documents for improving quality of medicines by adding new and updating existing
monographs in the form of Indian Pharmacopoeia (IP). It further promotes rational use of generic
medicines by publishing National Formulary of India, stated officials.
Lot numbers for 20 IPRS have been changed. These are Ketoconazole, Roxithromycin, Quetiapine
Fumarate, Cefotaxime Sodium, Glipizide, Piracetam, Ketorolac Tromethamine, Chloramphenicol,
Phenobarbitone, Lansoprazole, Tolterodine Tartrate, Erythromycin Stearate, Piroxicam, Pheniramine
Maleate, Lignocaine Hydrochloride, Zidovudine, Cyanocobalamin (Vit. B12), Aciclovir,
Dexamethasone Sodium Phosphate, Dicyclomine Hydrochloride.
According to the Commission, certain monographs require the use of a chemical reference substance or
a biological reference preparation or a reference spectrum. These are authentic specimens chosen and
verified on the basis of their suitability for intended use as prescribed in the Pharmacopoeia and are not
necessarily suitable in other circumstances.

Pharma expects a Brexit hit in 2017 and beyond

http://www.pharmatimes.com/magazine/2016/december/review_of_the_year_2016_brexit
After months of passionate campaigning and an incredibly tight race, the UK voted to leave the
European Union in a referendum held on 23 June. Before the vote, the pharma, life science and
healthcare sectors all threw their support behind the Remain campaign, stressing the importance of the
EU market to their businesses and workforces, and in the immediate aftermath they reiterated that a lot
of difficult questions will need to be addressed in the near future.
Mike Thompson, chief executive of the ABPI, said the decision "creates immediate challenges for future
investment, research and jobs in our industry in the UK", but added that the Association is "committed
to working closely with the government to agree what steps need to be taken to send a strong signal that
the UK is open for business". Steve Bates, chief executive of the BioIndustry Association, said that
while the fundamentals of UK bioscience remain strong, "several key issues for our sector are now in
flux". "Key questions about the regulation of medicine, access to the single market and talent,
intellectual property and the precise nature of the future relationship of the UK with Europe are now
upon us. This will require detailed and dispassionate thinking and the BIA will make its and its
members' expertise available to the government and its key agencies in the coming weeks and months as
we work through these complex issues."
Sarah Hanson, head of UK Life Sciences at international law firm CMS, said: "We must consider the
referendum's effect on the significant body of EU legislation which governs the development and supply
of medicines and medical devices. Companies engaging in any way with the European Economic Area
(EEA) markets will face increased regulatory burdens from having to deal with separate UK and EU
regulation, so the industry faces an arduous job ahead."
One major regulatory issue is that the European Medicines Agency (EMA) is likely to be forced to move
out of London and the UK will no longer be able to use it as its main regulatory body. Sweden and
Ireland are among the countries lobbying to be its new home. Meanwhile, the MRHA has been mooted
as a potential replacement regulator for the UK. The UK could also lose its position as the EU's most
popular location for phase I trials, and researchers in the country will no longer be eligible to apply for
EU grants or participate in EU-wide projects.
Meanwhile, in a statement, the European Federation of Pharmaceutical Industries and Associations
(EFPIA) stressed the importance of ensuring that the patient is at the centre of all subsequent decisions.
"EFPIA shares the common goal of ensuring rapid access to innovative medicines for patients across
Europe, as well developing a regulatory and policy environment that fosters innovation and supports the
research and development of new medicines to meet the needs of patients, healthcare systems and
society. As an industry, over the coming months, we are committed to engaging with stakeholders both
in Europe and in the UK to support these objectives."
But six months on, there is still almost no clarity on what Brexit will mean for the industry, or even the
UK as a whole, going forward. This is likely to be the case at least until the formal process of leaving
the EU begins (by activating Article 50 of the Lisbon Treaty). The government is hoping that this will
happen by March 2017, but some commentators have said that this is unrealistic now that the High
Court has ruled that the Brexit process can only start after a vote in parliament.
7

Nevertheless, with the decision setting in pundits have started to moot what pharma companies could do
to avoid too much damage such as a hoping for 'soft' Brexit where the UK remains part of the EEA, or
even relocating headquarters to mainland Europe. A new UK EU Life Sciences Steering Group is
working with stakeholders across the industry; it aims to secure regulatory co-operation with Europe,
predictable funding and collaboration for scientific research, access to the best talent, and the ability to
trade and move goods and capital across borders.
These fears have not been confined to pharma though many commentators have pointed out that the
NHS is likely to face many challenges, particularly in terms of recruitment. According to the Health &
Social Care Information Centre, the health service currently employs 9,814 doctors (8 percent of the
total) and 18,783 nurses and health workers (6 percent) who come from other EU countries. Although
they are unlikely to be forced to leave the UK, there are fears that some will choose to go anyway and
the supply of new recruits will thin. In the meantime, higher recruitment costs and an increased reliance
on agency staff would add to the NHS wage bill, exacerbating the squeeze on funding. This could in turn
mean that pharma will bear much of the pressure for pricing cuts.
Political turmoil also followed the vote, with PM David Cameron, who had campaigned for Remain,
resigning almost immediately, paving the way for former home secretary Theresa May to take his place.
With a new cabinet in place the UK life science sector could well have to deal with wider policy
changes over the next few years.
Violations force government to train pharma workers
Himani Chandna
Dec 20, 2016
http://www.hindustantimes.com/business-news/violations-force-government-to-train-pharmaworkers/story-3A6IsYWZsCZhX12cpDFHeL.html
Since the reputation of India that is known as the pharmacy to the world is at stake, the government has
begun sending health ministry staff to drug manufacturing hubs to train workers in good manufacturing
practice. The training sessions will continue for five years. Last month, the US drug regulator found
seven violations of manufacturing standards at Sun Pharmaceutical Industries Ltds formulations plant
in Mohali, Punjab. Also, the US Food and Drug Administration had issued a warning to Wockhardt for
violating current good manufacturing practice norms. We need to put stringent regulation practices in
place in accordance with foreign norms. Hence, we are planning workshops and hand-holding sessions
at various locations, GN Singh, drug controller general of India, told HT. As most units are in
Himachal Pradeshs Baddi, we have begun holding sessions from there.
Central Drugs Standard Control Organisation officials will visit the drug manufacturing hubs across
India. We are training CDSCO employees who will further train the staff of other units, said Singh
who heads the organisation. Nearly 7,000 manufacturing units in India produce and supply medicines
and vaccines worth over 2 lakh crore. The industry also exports to over 200 countries, as per
government estimates. In preparation of a training module, the central drug organisation will engage
with the drug producers so it can understand issues they face. Our objective is to train every drug
manufacturer, it said.

Pharmaceutical sector: 4-5 per cent drugs substandard, need concerted effort and stern action
Deepak Patel
January 3, 2017
http://indianexpress.com/article/business/business-others/pharmaceutical-sector-4-5-per-cent-drugssubstandard-need-concerted-effort-and-stern-action-4456296/
Three to five per cent of the drugs in the Indian market are still substandard and the central drug
regulator and state regulators would require to put in concerted effort and take stern actions to deal
with it, stated G N Singh, Drug Controller General of India (DCGI), in his letter to all state drug
regulators on December 30. Although the menace of spurious drugs has reduced over the years, the
percentage of Not of Standard Quality drugs reported in the country are still hovering around 4-5 per
centTherefore, I solicit your sincere cooperation for making a concerted effort to reduce to a great
extent the occurrence of substandard and spurious drugs even if it requires stern actions G N Singh
noted.
Watch What Else Is making News
Dalai Lama Initiates Annual 'Kalachakra Puja'
India has 36 drug regulators. Each of them keep testing the drugs on various quality parameters. Issues
related to quality/safety of drugs and pharmaceuticals manufactured, distributed and consumed require
to be resolved as a whole. Drugs comprise of a major portion of health budget and we cannot
compromise on the quality of our health service owing to the questionable standards of quality and
safety of drugs which may otherwise lead to failure in our health programmes, wasteful expenses and
loss of income and productivity, Singh mentioned in his letter.
According to a November 28 report of The Indian Express, in a major crackdown since March this year,
the drug regulators of seven states found that 27 medicines sold by 18 major drug companies in India
were of substandard quality, citing grounds such as false labelling, wrong quantity of ingredients,
discolouration, moisture formation, failing dissolution test and failing disintegration test.
Of the 18 companies, only two said they had stopped sale of the affected drug batches and just one said
the affected batch had been recalled. The tests on the 27 medicines were done by regulators of
Maharashtra, Karnataka, West Bengal, Goa, Gujarat, Kerala and Andhra.
Wishing the state regulators a happy new year, Singh stated in his letter: As we have the prime
objective to ensure the safety, quality and efficacy of drugs, we cannot lag behind in such issues and
cannot hurt the expectations of our society and global community. Understanding the seriousness of the
situation, the government is currently planning to amend the Drug and Cosmetics Rules, 1945, in order
to create an effective recall system for the drugs that are found to be substandard by any drug regulator
in the country. At present, neither there is a nation-wide drug recall system in the country nor are there
any rules mandating the companies to withdraw substandard drug batches from the market.

Outlook for pharma, education and microfinance in 2017

E Kumar Sharma
January 2, 2017
http://www.businesstoday.in/sectors/pharma/outlook-for-indian-pharma-in-2017/story/243377.html
What can the Indian pharma companies hope to look forward to in the new year? After all, market
headwinds in the form of drug pricing pressures , both in India and the US, and regulatory compliance
issues are expected to continue even in 2017. Some of the industry veterans feel a greater focus on smart
portfolio choices will get even more critical in 2017. This, they say, is crucial in the context of the
factors that characterized 2016. For the year just concluded stood out for the noise around regulatory
hurdles and price control pressures. In the Indian market, the moves by the government around bringing
in price control, be it for essential medicines or for medical devices like stents, was loud and clear. The
drug pricing pressures were an equal concern if not more, for Indian companies operating in their
biggest global market, the United States of America. The presidential election campaign put medicine
pricing as an important area for concern. This, on top of channel consolidation, added to the pricing
pressure. For instance, the US now has only about four large wholesalers and chains that source generic
drugs compared to about a dozen three years ago. This only means that they have a great deal of
bargaining power vis-a-vis the generic drug companies. These were the developments that characterized
the year.
Some of the companies, like Lupin or Sun Pharma, tried to overcome these through better portfolio
choices. This meant launching those products in the US which were either difficult to make or were
differentiated generics so that they had the benefit of limited or lower competition or where the
complexity of drug making ensured barriers to entry for many. Glenmark, for instance, pointed out that
it intends to build on the index for innovation. How that will play out for these companies needs to be
seen. However, company examples notwithstanding, the underlying message from some of the
announcements seems to be clearly driven by an end goal to look for opportunities to improve profits
and the return on capital employed.
The concerns in the new year do not seem to be materially very different from those in 2016. There was
the volatility in the emerging market currencies but that got played out in 2016. Concerns on this front
do remain even now. Other than that, concerns still hover around the drug pricing scenario and the
progress that many of them - be it Sun Pharma, Dr Reddy's and others - can make on the regulatory
compliance issues.
THE OUTLOOK FOR EDUCATION IN 2017
Expect to see greater use of technology
"India will start seeing a lot more use of technology in higher education," says Ajit Rangnekar, the
former dean of the Indian School of Business (ISB), with campuses in Hyderabad and Mohali. Already,
the concepts of flipped classrooms (pedagogical model where short video lectures are viewed by
students before they attend the class. The in-class time is devoted to discussing it or other related
activities) and MOOC (Massive Open Online Course) have already started taking off, especially in some
of the leading Indian institutions. The focus is expected to be not just on the way education is delivered
using technology, on the nuts and bolts of how we teach (the use of artificial intelligence, machine,
10

video technology, bigger telecommunication standards), be it 4G or 5G for facilitating learning, but the
thrust increasingly will also be on technology-related areas for career choice. This trend is not likely to
be confined to higher learning but is expected to play out across various levels of learning leading to
more being delivered electronically as and when students want. Some of this is being seen in the use of
fintech (or financial technology, where technology is applied for delivering financial services) for
instance.
On the regulatory front also, those who have been tracking the Indian education space see reason for
hope in the new leadership in the HRD ministry. The sector is likely to see a move towards giving
greater autonomy to government backed institutions -- like the Indian Institute of Managements (IIMs) - in deciding their future. This is more likely to be in the fashion of allowing them the freedom to
experiment with technology and with the new ways of reaching out to people. Finally, the IIM bill could
address all the major concerns of some of these institutions.
THE OUTLOOK FOR MICROFINANCE AND SMALL FINANCE BANKS IN 2017
It's wait and watch in the first quarter of the new year
January is the time the microfinance institutions add new clients and traditionally the sector has seen
players opening new branches. There is not much expected on this front as the sector --that was on a
near holiday after demonetisation -- has still to see loan disbursements and repayments returning to
normalcy. Therefore, many in the sector want to observe how the first quarter pans out and see if the
business returns. It has been a shock for the system said an industry insider.
Reason: There are two dimensions - one, is the simple fact about notes not being available and the
second, and more worrying to many, is the decline in business and the fact that this development lasted
for more than the week or two as was initially expected. An added dimension is that many of the new
small finance banks are expected to start their operations in the first quarter of 2017, which may not
necessarily be the best of times to start out (one could say that it could be a lesser challenge for the
urban and non-farm focused ones). What has baffled many is the inability to interpret the measures and
what exactly it could mean for the various stakeholders. For instance, is it a move that will boost the
payment banks? Indeed, it is still not clear how it will help them. Not many are bothered by the issue of
payment methodology, which may take a month or more but will eventually get sorted out, but the
bigger issue is of business taking off, which is taking time. Therefore, what one can gather at the
moment is that there is going to first six months of uncertainty and after that the expectation is that
business will get back on track.
Lupin receives US FDA nod for generic Evoxac capsule
BS Bureau
January 3, 2017
http://www.business-standard.com/content/b2b-pharma/lupin-receives-us-fda-nod-for-generic-evoxaccapsule-117010300190_1.html
Lupin Limited yesterday announced that it has received final approval from the US Food and Drug
Administration (FDA) to market its cevimeline hydrochloride capsule (30 mg). Lupin is expected to
commence promoting the product shortly. Cevimeline hydrochloride capsule (30 mg) is a generic
version of Daiichi Sankyo Incs Evoxac capsule, which is indicated for the treatment of symptoms of
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dry mouth in patients with Sjogrens Syndrome. Evoxac capsule had US sales of $ 40.8 million,
according to IMS MAT September 2016.
Natco launches hepatitis C drug Velpanat in Nepal
BS Bureau
January 3, 2017
http://www.business-standard.com/content/b2b-pharma/natco-launches-hepatitis-c-drug-velpanat-innepal-117010300201_1.html
Natco Pharma Limited has launched Velpanat a fixed dose combination medicine containing
sofosbuvir (400 mg) velpatasvir (100 mg) for the treatment of hepatitis C in Nepal. It is the first
generic version of sofosbuvir-velpatasvir fixed dose combination drug in Nepal. Sofosbuvir (400 mg)
and velpatasvir (100 mg) fixed dose combination is sold by Gilead Sciences Inc, under brand name
Epclusa.
Epclusa is the first all-oral, pan-genotypic, single tablet regimen for the treatment of adults with
genotype 1-6 chronic hepatitis C virus (HCV) infection. Epclusa is also the first single tablet regimen
approved for the treatment of patients with HCV genotype 2 and 3, without the need for ribavirin. Natco
has signed a non-exclusive licensing agreement with Gilead Sciences to manufacture and sell generic
versions of its chronic hepatitis C medicines in 101 developing countries. Natco has priced its generic
medicine, Velpanat, at an MRP of Rs 25,000 equivalent for a bottle of 28 tablets in Nepal.
The pharma industry worldwide is facing severe challenges that it has never faced before
Viveka Roychowdhury
December 21, 2016
http://www.expressbpd.com/pharma/cover-story/the-pharma-industry-worldwide-is-facing-severechallenges-that-it-has-never-faced-before/380153/
Titans of the pharma industry are adjusting their sails to adapt to an increasingly VUCA world where
volatility, uncertainty, complexity and ambiguity are the only constants. Daara Patel, Secretary General,
IDMA, shares his views on the strategies pharma leaders should adopt to lead and stay relevant in a
VUCA world, with Viveka Roychowdhury
What defines leadership in a VUCA pharma scenario?
To understand and accept that change can be sudden, as the recent invalidation of Rs 500 and Rs 1000
currency notes, and the ability to adjust to the change in national interest, is of supreme importance. The
pharma industry in India has been hit by turbulence at a pace that can be best described by the term
VUCA: volatile, uncertain, complex and ambiguous. Not only are the business leaders apprehensive but
most new entrants and mid-career pharma professionals are equally apprehensive about their career
prospects as well as the growth of the industry.
The pharma industry worldwide is facing severe challenges that it has never faced before. In India, the
scenario is even more grim with regulatory, pricing and PR challenges. To name a few:
En bloc banning of most FDCs
NPPA crossing its brief by bringing more and more formulations under price control
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NPPA insisting on revised prices being made effective retrospectively.

Serious regulatory issues with FSSAI
Proposed amendment to definition of New Drugs from four to 10 years.
Taxation on pharma products to go up by at least three per cent due to implementation of GST. Either
industry will absorb the increase which they can ill afford or the government increases prices which the
patient can ill afford. NGOs targeting and attacking the pharma industry and accusing it of profiteering
and acting against the interest of the patients. The Damocles sword Total dependence on China for
APIs which is more dangerous than going to war with China
Lack of support to R&D.
Due to the above reasons there is a lot of uncertainty in the industry and further investments and
expansion plans are stalled.
How have pharma leaders and corporations in established markets like the US, EU etc, changed their
strategies?
The US, EU pharma industries are facing wide-ranging changes. Above all, the rise of emerging market
economies and increasing price pressures on established pharma markets require extensive adjustments
to pharma business models. Despite a generally positive estimation of the current business climate, the
global pharma industry faces various challenges that endanger their current and future business
development. Nearly all of them consider themselves affected strongly by VUCA challenges.
What learnings do these paradigm shifts have for pharma leaders and corporations in the emerging
markets like India APAC regions?
Leaders must provide clarity so that work assignments and goals are not as ambiguous as the
environment. Ambiguity doesnt paralyse workers; it makes them insecure and stirs them up. Competent
employees, when faced with ambiguity, will do what they are most comfortable doing in order to feel as
if they are contributing something appropriate. Doing something, whether its helpful or not, makes us
feel good. A leader must provide clear direction and synchronise the efforts of others while continually
communicating any adjustments.
Who are the new business icons for the pharma industry and why are they the new role models?
Leading in turbulence demands the ability to utilise all facets of the human mind. Even the most
impressive cognitive minds will fall short in the VUCA world it will take equal parts of cognitive,
social, emotional, spiritual and physical intelligence to prevail. To be responsive and resilient, with the
ability to ride out turbulent forces that cannot be avoided, and to pivot quickly to seize opportunity
when it presents itself. The days of the single great leader are gone. In the VUCA world, the best
leaders are the ones who harness leadership from everyone. Apart from other leaders, CEOs of
multinationals in the West have a huge challenge in meeting growth targets. They are aware that bulk of
their sales will come from countries like India, where prices of multinational companies are not
affordable. It would be a real challenge for them to have a differential pricing mechanism in order to
ensure that the sales targets are met and patients can also afford the medicines.

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Scientists discover new natural source of potent anti-cancer drugs

Date: December 20, 2016
Source: The Scripps Research Institute
https://www.sciencedaily.com/releases/2016/12/161220174720.htm
Scientists from the Florida campus of The Scripps Research Institute (TSRI) have developed an efficient
process to rapidly discover new "enediyne natural products" from soil microbes that could be further
developed into extremely potent anticancer drugs.The study highlights microbial natural products as
abundant sources of new drug leads. The researchers' discovery process involves prioritizing the
microbes from the TSRI strain collection and focusing on the ones that are genetically predisposed to
produce specific families of natural products. The scientists say this process saves time and resources in
comparison to the traditional approaches used to identify these rare molecules.The study, led by TSRI
Professor Ben Shen, was published in the journal mBio.Shen and his colleagues uncovered a new family
of enediyne natural products, called tiancimycins, (TNMs) which kill selected cancer cells more rapidly
and completely in comparison to toxic molecules used in FDA-approved antibody-drug conjugates
(ADCs) -- monoclonal antibodies attached to cytotoxic drugs that target only cancer cells.The scientists
also discovered several new producers of C-1027, an antitumor antibiotic currently in clinical
development, which can produce C-1027 at much higher levels.It has been more than a decade since
Shen first reported on the C-1027 enediyne biosynthetic machinery, and he speculated then that the
knowledge obtained from studying biosynthesis of C-1027, and other enediynes, could be used for the
discovery of novel enediyne natural products."The enediynes represent one of the most fascinating
families of natural products for their extraordinary biological activities," Shen said. "By surveying 3,400
strains from the TSRI collection, we were able to identify 81 strains that harbor genes encoding
enediynes. With what we know, we can predict novel structural insights that can be exploited to
radically accelerate enediyne-based drug discovery and development.""The work described by the Shen
group is an excellent example of what can be achieved by coupling state of the art genomic analyses of
potential biosynthetic clusters and modern physicochemical techniques," said David J. Newman, retired
chief of the National Cancer Institute's Natural Products Branch. "As a result of their work, the potential
number of enediynes has significantly increased."Shen's method of strain prioritization and genome
mining means a far more efficient use of resources involved in the discovery process, targeting only
those strains that look to produce the most important natural compounds."This study shows that the
potential to rapidly discover new enediyne natural products from a large strain collection is within our
reach," said TSRI Research Associate Xiaohui Yan, one of four first authors of the study. "We also
show the feasibility of manipulating tiancimycin biosynthesis in vivo, which means that sufficient
quantities of these precious natural products can be reliably produced by microbial fermentation for drug
development and eventual commercialization."

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Worlds Drug Regulatory Authorities to Work Towards Global Access to Quality Medical
Products
Pretoria, 24 November 2016
http://www.who.int/medicines/news/wdg-authorities-work-tgaqmp/en/
Africa Rapidly Progressing to Regional Medicines Agency
Pretoria, 24 November 2016 Underfunding, under-staffing and weak policies are hampering national
regulatory authorities capacity to advance access to quality medical products and safeguard patient
safety, particularly in developing countries. To address these challenges, the worlds regulators will
meet in Cape Town on 29 November-2 December for the biennial International Conference of Drug
Regulatory Authorities (ICDRA), whose theme this year is Patients are waiting: how regulators
collectively make a difference.
Organised by the Government of South Africa and the World Health Organization (WHO), ICDRA
2016 will focus on the need for greater international collaboration between national regulatory
authorities (NRAs) to improve their efficiency and expand patient access to safe and effective
diagnostics, medicines, vaccines and medical devices in all countries. Africa will be a special focus of
discussions and plans, including the rapid progress made in efforts to build an African Medicines
Agency.
90% of our regulatory assistance to countries is focused on Sub-Saharan Africa, said Dr Suzanne Hill,
WHO Director for Essential Medicines and Health Products. The region has made good progress
recently to improve regulatory performance and ensure that patients can access safe and effective
essential health products. But we need to keep up the momentum, and governments must invest more
resources into this area. Strengthening the role of regulatory authorities will bring us closer to realising
universal health coverage and universal access.
WHO estimates that at least three out of 10 NRAs in the world are not fit for purpose, largely due to
limited resources and low recognition of their crucial role in their countries health systems. Even the
more established NRAs in high-income countries face resource challenges and administrative
bottlenecks due to the increasingly globalised nature of pharmaceutical manufacture and trade, and the
emergence of innovative products such as biotherapeutics and sophisticated medical devices which
require new regulatory know-how and approaches.
If not dealt with, these challenges can result in long waiting times for products to receive authorisation
and reach patients, shortages of vital medicines in health facilities and the risk of unsafe, unregulated
products on markets. The solution WHO has been proposing for a number of years is harmonization of
quality standards and greater collaboration between NRAs to improve efficiency, cut costs and expedite
market entry of life-saving products.
Work-sharing schemes between countries from the same region and reliance mechanisms, whereby
NRAs from high-income countries provide assistance to NRAs in developing countries, have begun to
bear fruit. For example, a collaborative registration scheme led by WHO in partnership with 22 African
NRAs across economic regions has facilitated the registration of 152 essential WHO-prequalified
medicines and reduced approval timelines from several years to an average of 78 days. Similar
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initiatives supported by WHO through training and policy support are improving regulatory performance
in the East African Community (EAC) and the South African Development Community (SADC).
Another major success story is the recent expansion of the African Vaccine Regulatory Forum
(AVAREF), a platform for African NRAs to collaborate on regulating vaccine clinical trials in order to
expedite and improve access to these products. AVAREF was a key actor in the fast-track approval of
clinical trials of candidate Ebola vaccines during the West Africa Ebola epidemic.
Since AVAREFs establishment 10 years ago, new collaborative networks have taken shape, such as the
African Medicines Regulatory Harmonization (AMRH) initiative, providing the African region with
new opportunities to improve and harmonize regulatory practices. With a new structure, governance and
strategy, AVAREF is now starting to include medicines and other health products for evaluation as well
as capacity building. The initiative is developing into a powerful platform for African regulatory
harmonization and improved efficiency.
AVAREF embodies the ambitious plan to expand access to quality medical products in African
countries and hinges on strengthening national regulatory authorities on the continent, said Dr Rufaro
Chatora, WHO Representative in South Africa. Along with AMRH and WHOs support of
harmonization and capacity building in our region, AVAREF is laying the ground for the formation of
the African Medicines Agency. Our hope is that once the Agency is fully established, access to quality
medicines and other health products in Africa will pick up dramatically.
Successful harmonization initiatives in Africa and elsewhere speak for themselves, said Dr Hill. Im
confident that the Cape Town meeting will take us one step further to strengthened international
collaboration between countries so that we can protect patients and honour our commitment to the
sustainable development agenda of access to health for all.
Note to Editors
The International Conference of Drug Regulatory Authorities (ICDRA) provides drug regulatory
authorities of WHO Member States with a forum to meet and discuss ways to strengthen collaboration.
ICDRA meetings have been instrumental in guiding regulatory policies and priorities for action in
national and international regulation of medicines, vaccines, biomedicines and herbals.
The conferences have been held since 1980, with the aim of promoting exchange of information and
collaborative approaches to issues of common concern. This years conference, whose theme is Patients
are waiting: how regulators collectively make a difference places a strong focus on public health and
the need to harmonize standards globally so that regulators can strengthen their efforts to address current
challenges, such as the impact of free trade and expanded markets on access to quality medical products,
and new approaches needed to regulate increasingly sophisticated products, such as biotherapeutics and
innovative medical devices.

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Researchers Call for Retraction of Paper that Questions HPV Vaccine

Jef Akst
December 23, 2016
http://www.the-scientist.com/?articles.view/articleNo/47853/title/Researchers-Call-for-Retraction-ofPaper-that-Questions-HPV-Vaccine/

Last month (November 11), a Japanese team of researchers published a study in Scientific Reports
describing the negative outcomes suffered by mice given the vaccine for human papillomavirus (HPV).
But researchers and doctors have criticized the study and are now calling for its retraction, Science
reported. The paper describes how vaccinated animals exhibited neurological phenotypes, including
limited mobility, and suffered damage to the hypothalamus and other brain regionseffects the authors
suggest may shed light on recent reports of the vaccines adverse effects in humans, similar to the
symptoms of chronic fatigue syndrome. But the mice received doses that were proportionally a
thousand times greater than that given to people, along with a toxin that makes the blood-brain barrier
leaky, Science notes. Basically, this is an utterly useless paper, a waste of precious animals, David
Gorski, a surgical oncologist at the Barbara Ann Karmanos Cancer Institute in Detroit, Michigan, wrote
on his Orac blog.
The HPV vaccine, originally licensed in 2006, is now approved in more than 120 countries, and early
surveillance has suggested that rates of cervical cancer, a disease linked to HPV, are already starting to
decrease. But as complaints of various vaccine-associated symptomsincluding headache, fatigue, pain,
and difficulty walkingstarted to crop up, the rates of vaccination around the world, including in Japan,
began to decline. In June 2013, after several Japanese media outlets covered the reported side effects,
the health ministry stopped recommending that women receive the HPV vaccine and requested an
investigation into its benefits and risks. Even after an investigative panel found no evidence that the
vaccine was causing the adverse events, however, Japans health ministry never restored its proactive
recommendation, Science reported, and vaccination rates in the country have continued to drop.
The new study adds fuel to this anti-vax fire. Vaccinating mice with larger doses while treating them
with a pertussis toxin to help the vaccine reach the central nervous system, Toshihiro Nakajima of
Tokyo Medical University and colleagues found that the mice suffered impaired mobility and tail
movement as well as brain damage and abnormalities. In response, researchers have sent a pair of letters
to Scientific Reports and its publisher, the Nature Publishing Group, criticizing the studys methodology
for its gross over dosage and manipulation and its lack of adequate controls to control for bias,
Science reported. Nakajima defended his work writing in an email to Science: Our manuscript was
formally published after an intensive scientific review done by reviewers and by the editorial board of
Scientific Reports. Regarding the dose, he added, this is just the first paper and dose-dependency
could be one of the interesting experiments in the future.

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New CRISPR-Cas Enzymes Discovered

Kerry Grens
December 22, 2016
http://www.the-scientist.com/?articles.view/articleNo/47845/title/New-CRISPR-Cas-EnzymesDiscovered/
Microbes use a number of CRISPR-Cas systems for immunity, but its the class 2 system, typically
utilizing the nuclease Cas9, that has been adapted for genome editing. A metagenomics search of
microbes sampled from soil, groundwater, an acid mine drainage site in Colorado, and a Utah geyser has
led to the discovery of additional class 2 CRISPR-Cas programs, including the first Cas9 identified in
archaea and two small Cas enzymes in bacteria. Researchers published their findings in Nature today
(December 22). Its really cool to unearth gold out of the metagenomic dark matter, said Rodolphe
Barrangou, who studies CRISPR at North Carolina State University and was not involved in the study.
Theres so much more in nature than people appreciate.
Although CRISPR is perhaps best known as a laboratory tool for tinkering with genetic sequences and
functions, its origins lie in defending microbes from invaders. Scientists developed CRISPR as a
genomic editor from bacteria grown in the lab, but countless microbes remain uncultivatedthat is, not
isolated and grown in culture. Therefore, the potential for discovering new forms of CRISPR is vast.
Over the past decade, Jillian Banfield of the University of California, Berkeley, and colleagues have
been collecting microbes from various locations, extracting their DNA, and reconstructing their
genomes. The result is a terabase-scale genomics collection of uncultivated bugs, which was mined for
undiscovered CRISPR systems in the present study. We hoped to find new [CRISPR] systems and we
thought there was a reasonable chance given the size and diversity of the database, Banfield told The
Scientist. Banfields team searched the genomes for sequences that were both near cas1, which encodes
a conserved CRISPR protein, and close to characteristic sequence repeats. The researchers found
sequences for Cas9 in two archaeal genomes extracted from the Richmond Mine in Iron Mountain,
California. Previously, archaea were known to use class 1 CRISPR systems, but class 2 had only been
identified in bacteria.
We dont really know how it performs, because that has not been achieved in the laboratory yet, said
Banfield. Archaea have different biology. The fact that [my collaborators] havent yet managed to
show its function probably means there are components of the system that we dont yet know about.
The group also uncovered new types of Cas proteins from groundwater and soil bacteria, dubbed CasX
and CasY. Theyre really small, especially CasX, said Banfield. That means its potentially more
useful. CasX is made up of only 980 amino acids, whereas other Cas enzymes are larger. For instance,
the commonly used Cas9 from Staphylococcus pyogenes contains 1,368 amino acids, while a smaller
one from S. aureus is made up of 1,053 amino acids (CasY is around 1,200 amino acids). This is
important biotechnologically, because if you look at if from the angle of genome editing, the delivery of
small genes into cells is much easier than the delivery of large genes, said Rotem Sorek of the
Weizmann Institute of Science in Israel who was not involved in the work.
In partnership with UC Berkeleys Jennifer Doudna, Banfields team demonstrated that CasX and CasY
are functional. The researchers introduced CRISPR-CasX and CRISPR-CasY into E. coli, finding that
they could block genetic material introduced into the cell. This warrants the investigation of whether

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this could do genome editing, Barrangou said of CasX. Banfield said Doudnas group is continuing to
characterize the function of these enzymes.
CasY came from bacteria within a large and only recently described group of microbes called the
Candidate Phyla Radiation, which Banfield worked into an updated tree of life earlier this year. She
added that this latest study is an example of the way metagenomics can tap the riches of a microbial
universe that was once out of reach for scientists, but now at their disposal. This is a case in point for
what I think will be an avalanche of new proteins and pathways and systems that hold unimaginable
biotechnology and medical value.
Ebola Vaccine Is the First to Block Infection
Alice Park
Dec. 22, 2016
http://time.com/4611239/ebola-vaccine-infection-virus/
Researchers report encouraging results from a trial of an Ebola vaccine that is the first to prevent
infection from the deadly virus Since the outbreak of the most recent Ebola epidemic in West Africa,
more than 11,000 people have died and more than 15,000 people have been infected with the virus.
While some drug treatments have been marginally effective, no vaccine to protect against infection has
yet been developed, although a number are currently being tested. One of those, developed by the Public
Health Agency of Canada and manufactured by Merck, showed early promise in 2015. Now, a new
report published in the journal Lancet provides even more encouraging results that suggest it may be the
first vaccine to prevent infection with Ebola.
The trial involved more than 11,000 people living in Guinea, one of the West African countries that bore
the brunt of the recent Ebola epidemic. Once a case of Ebola was confirmed, a list of people who had
come in contact with the patient was compiled, and they were randomly assigned to either receive the
vaccine, called rVSV-ZEBOV, immediately or three weeks later. All participants were tested for
presence of Ebola. After 10 days, there were no cases of Ebola infection among those who were
vaccinated, while 23 people were diagnosed with Ebola in the group that did not receive the vaccine
immediately.
The positive results led the study organizers to provide the vaccine to all people who had come in
contact with Ebola patients. That included family members who lived with patients and were exposed to
their clothing or linens, as well as the next ring of people who had interacted with these contacts. Side
effects from the vaccine, which were monitored up to 12 weeks after immunization, were relatively rare
and included headache, muscle pain, fever and anaphylaxis. More studies will be conducted on the
people who were vaccinated to see if their immune responses indeed were boosted by the shot. In the
meantime, based on the positive early results, Merck agreed to provide the World Health Organization
with 300,000 doses of the vaccine for emergency use in health care workers and people at highest risk of
infection in an effort to control spread of the virus. If the positive results are confirmed and repeated, the
vaccine could play a critical role in stopping the Ebola epidemic and preventing future outbreaks.

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Pharma and Europe 2017: A Year of Greater Uncertainties

Dec 21, 2016
By Reflector
http://www.pharmexec.com/pharma-and-europe-2017-year-greater-uncertainties
2016 has been the year of the unpredictable and the uncertainties that this has generated will multiply
in 2017 and dominate the agenda in Europe, in pharmaceuticals as much as in healthcare, and in the
broader and highly influential world of politics. For pharmaceuticals, the greatest uncertainty is
how far Europe is going to remain a market that innovative companies wish to engage with. The
business climate, which for many years has been rather benign, despite the frequent cries of "wolf" from
drug industry bosses, is now deteriorating rapidly.

All drug companies are faced with tougher pricing negotiations that are driven by ever-tighter controls
on national health system funding across Europe. And in 2017 it will get tougher, as individual
European countries combine their strength to negotiate jointly with drug firms on prices for new
medicines. Ireland is set to join with Austria, Belgium, the Netherlands and Luxembourg in a new
coalition to boost their collective bargaining power, and similar schemes are gathering impetus in the
Nordic countries, the Balkans, and in central and eastern Europe. At the same time, innovators are
increasingly challenged by a rising tide of scepticism shared now by many senior politicians, as well
as by the customary critics in the health activist community. Even the European Union's normally sedate
health council has called for a review of incentives for drug research, alarmed by allegations of
rapacious drug firms bending the rules to extract unfair advantage from patent term extensions and
market exclusivity deals granted to orphan drugs.
Meanwhile, the fragile attempts that had been underway to build a consensual approach to future drug
development and regulation at the European Medicines Agency, in the EU's public-private research
venture IMI2, or in closer links between payers, patients and regulators are being undermined by the
accelerating fragmentation of Europe's own political structures.
The most obvious and immediate imponderable is Brexit the planned UK withdrawal from the
European Union. Not only will this exclude one of the continent's biggest buyers from the EU's single
market as from 2018 (and consequently oblige companies to start obtaining separate marketing
authorizations for products there). It will also remove the expertise of UK government officials (with
their traditionally industry-friendly attitudes) from EU deliberations on pharmaceutical policy. And at
the practical level, it will oblige EMA to quit its London headquarters and relocate elsewhere in Europe
a prospect that is an administrative nightmare in itself, but also, as its bosses openly admit, that is
already damaging staff motivation and impeding recruitment, with obvious implications for operational
efficiency.
Brexit will also require major readjustment to existing and pending European initiatives on everything
from clinical trials regulation to health technology assessment, and from digital health to modernized
pathways to medicines authorization. What will happen, for instance, to longstanding European attempts
to unify the scattered clinical trial authorization procedures that have bedevilled the start-up of multicountry new-drug investigations? The finishing touches are being put to a single procedure designed to
come into effect across the EU, dependent largely on mutual trust among national regulators, and backed
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up by a legislative framework. Since the UK is the site of so many international clinical trials, and the
generator of as many too, its departure from the EU makes the outlook for a single system now look like
a lost dream. The same will be true for the increasingly troubled bid to modernize European drug
authorization procedures the adaptive pathways project spearheaded by EMA officials, which has
enjoyed strong support from the UK. Take the UK away from those deliberations, and the field will be
open for countries with a more conservative stance notably Germany to block the process. The
same fate is likely for the current attempts to find common ground across Europe on health technology
assessment, where the UK's national reimbursement organization, NICE, has been at the forefront in
seeking greater coordination often in the teeth of objections from other member states.
But Brexit will also have wider consequences, in the way that it has reinforced a centrifugal trend in the
European Union. The sense of common purpose that has driven European integration for more than 50
years was already losing momentum in the wake of the 2008 economic crisis, which set richer countries
against poorer. A migration crisis and a growing terrorist threat have added fuel to popular
disenchantment with the entire European concept in many parts of the continent. Brexit is turning those
fault-lines into fractures, reversing half a century of European construction. The EU itself, and its own
institutions, are accordingly losing a sense of purpose and the authority that goes with it.
The European Commission, once the proud defender of EU law, is now unpopular with member states
increasingly resentful of being told what to do, and who now also flirt with the idea of going their own
way. The Commission, thus embattled, is increasingly hesitant in tackling national governments that
ignore legislation for their own national purposes. In, for instance, the controversial (and economically
significant) case brought by the drug industry against France and Italy for officially substituting cheaper
cancer treatments for more expensive eye medicines, will the Commission now lack the courage to
deliver its long-awaited ruling? And in the face of widespread disenchantment with its mission to
stimulate cooperation, will it still dare to promote cross-border care and the planned European network
of specialized research and treatment centres, or to push for common approaches to personalized
medicine or the orderly development of digital health?
The unquestioned opportunities for major developments in health and medicine as the world moves into
2017 will be taken up in some parts of the world. The potential of new science and the deeper
understanding of disease processes offer unprecedented hope for health, and will be seized on with both
hands by many players. The question for Europe in 2017, however, is whether those opportunities will
also still be seized by Europeans, or whether Europe has lost its way and will revert to the parochialism
of nationalist views and to division and dissension and consequently miss out on its future.
Pharma M&A Market: Latest Challenges and Opportunities
Dec 14, 2016
By Peter Young
http://www.pharmexec.com/pharma-ma-market-latest-challenges-and-opportunities
The last few years have been a positive period overall for both the pharma and the biotech industries on
many fronts. Most importantly, the number of new drugs approved and under development has
escalated for both pharma and biotech companies. Many of these are driven by new methods, such as
immuno-oncology, personalized medicine, stem cells, and biologics. We are also witnessing the
development of a greater number of drugs that cure diseases rather than just extend life.
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The valuations of both pharma and biotech companies in the public and M&A markets soared up until
the end of 2014 in part because of these positive developments, but share prices and public valuations
have been volatile since then with the drug pricing controversies. Public biotech shares have been hit
particularly severely since the end of 2014, and as a result the IPO market began to cool off in the
second half of last year. This is creating a difficult equity financing environment for biotech companies
which, in turn, has affected the choices available to biotech companies to continue to fund their
companies.
Pharma M&A
Through the third quarter of 2016, 37 deals were completed worth $117 billion compared to 56 deals
completed worth $200 billion in 2015. From a historical perspective, this is a very strong volume of
activity for the industry. However, from an annualized point of view, this represents a decrease in the
dollar activity compared to last year, and a slight decrease in the number of deals. The main driver of
this moderate slowdown has been the absence of the mega tax inversion related deals that we saw last
year. However, the clampdown on the tax rules by the U.S. Treasury Department strongly discouraged
those companies pursuing tax inversion deals and killed a number that were in the works as of the end of
last year.
In part because of that, there were fewer mega deals, with only two large deals completed, the $31
billion acquisition of Baxalta by Shire and the $40.4 billion acquisition of Allergans Generics Business
by Teva. Drug makers are acting as both buyers and sellers, forming strategic alliances and swapping as
they shore up their core businesses, exit non-core units, and use or seek tax inversion advantages. As of
September 30, 2016, the value of the deals announced but not closed was $7 billion (20 deals), a solid
number of deals, but a weaker dollar volume in the pipeline. The pipeline was $240.4 billion (16 deals)
at the end of December, but the massive Pfizer/Allergan deal was cancelled and took a large dollar
amount off the table as a result.
Biotech M&A
Biotech M&A activity has almost always been modest historically, with small spurts of activity from
time to time. Through the third quarter of 2016 there were 29 biotech M&A deals completed worth $14
billion compared to 31 deals worth $19 billion completed in 2015. 2016 activity is on track to exceed
2015 in terms of the number of deals. The dollar volume trajectory is less clear.
This pick-up in activity is partly due to the major drop-off in biotech IPOs since the later part of last year
as the market has turned against biopharma companies. Through the third quarter, only 22 IPOs have
been completed this year compared to 61 for all of last year and 72 the year before. On a dollar basis, the
picture is even more severe with only $1 billion raised in IPOs during the third quarter, compared to $5
billion the year before. Secondary offerings have also been adversely affected. Sealed off from high
valuation equity offerings, the biotech companies are less fortunate than they were in 2013, 2014 and
most of 2015 when they were able to raise money at high valuations. In many cases, it is not even an
issue of valuation and the biotech companies have not been able to go public at all. As a result, the

22

biotech companies who are in Phase II and Phase III clinical trials where the cash consumption is high
and have been forced to either sell or to partner in order to deal with their shortage of cash.
The pipeline of M&A deals as of September 30, 2016 was weak when the value of deals announced but
not closed was very modest at only $0.6 billion on only 1 deal. However, that has picked up as biotech
companies are being picked off as acquisition candidates. There has been a litany of companies who
have announced that they are exploring their strategic alternatives.
Outlook: Pharma M&A
Young & Partners expects pharma M&A activity in 2016 to fall modestly in terms of numbers of deals
and more significantly in terms of dollars. The shutdown of the large inversion deals contributed to the
dollar slowdown. However, volume will still be significant in 2017 and beyond, driven by the
restructuring and strategic needs of the pharma companies and the residual impact of what has been a
feeding frenzy. This is being fueled by the massive business restructuring that is happening in pharma
and the consolidation that is occurring both on the generic and non-generic sides of the business.
Pharma companies are modifying their business portfolios to focus on leading positions and to exit
weaker positions, and non-core and mature/established products, to search for growth, to attempt to
replace lost or soon to be lost revenues, and to drive for scale and cost reduction through consolidation.
Outside of M&A, the need to fill the shrinking drug pipeline is also facilitated by in-licensing
arrangements and the formation of partnerships and joint ventures involving both pharma and biotech
companies.
Therefore, in spite of the headwinds from the current ruckus about drug pricing, we believe there will be
strong pharma M&A volume ahead of us, but moderately curtailed on a dollar basis by the inversion
rules now in place.
Outlook: Biotech M&A
The primary biotech M&A theme has been pharma and big biotech acquisitions of biotech companies
for pipeline enhancement. The most promising biotech companies over the previous three years were
able to go public first and attract significant interest and high prices later. The surge in IPOs gave
biotech companies more flexibility as to whether and when they exit via a sale. However, the recent
slowdown in IPOs will drive many companies to either sell themselves or raise funds via partnering
deals or discounted private placements.
Therefore, M&A volume and partnering deals will likely increase significantly in 2017, but still be well
below that of the pharma industry.
Implications for Senior Management
For ethical pharma companies, there will continue to be a wide variety of tools to acquire revenues and
pipeline drugs, but the valuations are challenging, particularly for promising drugs in late stage clinical
trials and for companies with strong products. The challenge will be to pick the right overall mix of
23

M&A, licensing, and partnering to accomplish corporate strategic goals and defend and deliver
shareholder value.
The generic pharma companies will continue to face a number of industry challenges. This will result in
a continuation of the current industry consolidation and selective strategies around diversification. For
biotech companies, public and private, the future is exciting from the drug development side, but
troubling on the private funding, IPO, secondary equity financing, and M&A fronts. Time will tell
whether the very public attack on drug pricing will ease up and/or force changes in the industry.
CDC: 10 Most Dangerous Drugs Linked to Overdose Deaths
Monthly Prescribing Reference
December 22, 2016
http://www.empr.com/news/cdc-10-most-dangerous-drugs-linked-to-overdose-deaths/article/580540/
HealthDay News Drug overdose deaths increased 23% between 2010 and 2014, with 47,055
Americans dying in 2014, according to findings published in the December 20 issue of the U.S. Centers
for Disease Control and Prevention's National Vital Statistics Reports. The 10 most dangerous drugs in
terms of overdose mortality in 2014 were: heroin (23% of overdose deaths); cocaine (12.4%);
oxycodone, (11.5%); alprazolam (9%); fentanyl (8.9%); morphine (8.5%); methamphetamine (7.9%);
methadone (7.4%); hydrocodone (7%); and diazepam (3.7%). The mortality rate specifically from
fentanyl more than doubled in a single year, rising from 1,905 deaths in 2013 to 4,200 deaths in 2014.
Updated numbers from the CDC, published in the December 16 early-release issue of the CDC's
Morbidity and Mortality Weekly Report, also show that 52,404 people died from a drug overdose in
2015, and 33,091 of those deaths (63.1%) involved a prescription or illicit opioid. In 2015, mortality
rates for all synthetic opioids other than methadone increased 72.2%, while heroin death rates increased
20.6%. The increases cut across all demographic groups, regions, and numerous states. In examining the
regional impact of overdose deaths from 2014 to 2015 in 28 U.S. states, the authors of the MMWR
report found that the three states with the largest percentage increases in rates of deaths due to synthetic
opioids other than methadone were New York, Connecticut, and Illinois. The three states with the
largest percentage increases in rates of heroin deaths were South Carolina, North Carolina, and
Tennessee, while Connecticut, Massachusetts, Ohio, and West Virginia had the largest total rate
increases in heroin deaths.
Ibuprofen Use in Pregnancy: Less Dangerous Than Thought?
Daniel Holland, PharmD
DECEMBER 22, 2016
http://www.pharmacytimes.com/contributor/daniel-holland-pharmd/2016/12/ibuprofen-use-inpregnancy-less-dangerous-than-thought
Ibuprofen prematurely closes the hearts ductus arteriosus, increases reactive oxygen species, and
inhibits placenta vascularization. Ibuprofen use late in pregnancy can reduce the production of the
prostaglandins responsible for maintaining a patent ductus arteriosus. Pregnancy is an energy-intensive
process spurring mitochondrial production of large amounts of reactive oxygen species. These free
radicals reduce the vascularization of the intervillous space and limit the supply of nutrients to the
developing embryo.1 The ductus arteriosus typically closes at or within days after birth once the
24

newborns pulmonary circuit begins use. A patent ductus arteriosus allows small clots to bypass the
lungs and cause a stroke. In contrast, premature ductus arteriosus closure is clinically insignificant for
most births because the blood is no longer bypassing the lungs in the airless environment of the womb.
However certain diseases require a patent ductus arteriosus at birth for patient survival. For example,
infants with dextro-transposition of the great arteries need the right-left shunting through the ductus
arteriosus to circulate blood to the systematic circulation. Dextro-transposition of the great arteries is a
rare disease (1 in 3300 births) often identified in prenatal screening.
Ibuprofens vascularization inhibition may predispose newborns to low birth weight and its
complications. Recent findings contradict the belief that NSAIDs increase the risk of miscarriage (and
by extension pre-term birth). The failure to treat ongoing severe pain adequately during pregnancy can
cause pregnancy-endangering high blood pressure, depression, and anxiety. The Food and Drug
Administration has maintained their recommendation to women to consult with their gynecological
provider before using NSAIDs during pregnancy.
A team of researchers from Norway have found second and third trimester ibuprofen exposure has no
effect on birth weight or pre-term birth in a new study published on December 9, 2016 by PLOS ONE.1
The authors used data on 28597 siblings from the Norwegian Mother and Child Cohort Study and the
Medical Birth Registry of Norway. A slim fraction (1080) of siblings had ibuprofen exposure and the
remainder had no NSAID exposure. The authors excluded siblings from multiple pregnancies, with
missing information, or exposed to a non-ibuprofen NSAID.
The first trimester was the most common time of ibuprofen exposure. Some mothers may have been
unaware of their pregnancy at the time of exposure. One in three newborns had multiple trimester
exposure. Ibuprofen-using mothers were less likely to have tertiary education or used folic acid
supplements. These mothers were more likely to consume alcohol or smoke during pregnancy than nonibuprofen using women.
Ibuprofen exposure had no effect on gestational age at delivery and little effect on birth weight.
Ibuprofen-exposed newborns were at slightly increased risk of delivery before 37 weeks or a birth
weight less than 2500 grams. Mean birth weight was less among newborns exposed during first or
second trimester. However, the birth weight reduction was statistically significant but clinically
insignificant among term infants. A 79 gram difference in mean birth weight between exposed and
unexposed newborns does not suggest any impact on infant development or health outcomes. Exposure
duration had no effect on birth weight.
Potential confounders included newborn sex, birth order, maternal age, parity, pre-pregnancy maternal
BMI, education, smoking status, and alcohol intake during pregnancy. The sibling design minimizes
genetic and environmental confounders. This study was able to control for smoking history and alcohol
intake that are well-known strong factors on birth weight. Confounding by indication is unavoidable but
the authors adjusted for the most common indications for NSAID therapy. The authors could not
evaluate for a dose-response relationship because the Norwegian databases lack dosage information.
Prenatal ibuprofen exposure has little effect on birth weight and no effect on gestational age at delivery.
Uncontrolled study factors or selection bias may have caused the small change in mean weight. Pregnant
women should consult their gynecological provider, and weigh the risks and benefits, before using any
NSAID therapy.
25

Works Cited
Nezvalova-Henriksen K, Wood M, Spigset O, Nordeng H. Association of prenatal ibuprofen exposure
with birth weight and gestational age: a population-based sibling study. PLoS One. 2016; 11(12):
e0166971. doi:10.1371/journal.pone.0166971.
Facts about dextro-Transposition of the Great Arteries (d-TGA). Centers for Disease Control and
Prevention Website. https://www.cdc.gov/ncbddd/heartdefects/d-tga.html. Updated November 14, 2016.
Accessed December 14, 2016.
FDA Drug Safety Communication: FDA has reviewed possible risks of pain medicine use during
pregnancy. US FDA Web site. http://www.fda.gov/Drugs/DrugSafety/ucm429117.htm. Published
January 9, 2015. Accessed December 14, 2016.
Screening: The Key to Increasing Immunization in the Pharmacy
Jeannette Y. Wick, RPh, MBA, FASCP
DECEMBER 22, 2016
http://www.pharmacytimes.com/resource-centers/immunization/screening-the-key-to-increasingimmunization-in-the-pharmacy

Record-keeping is one of the greatest challenges to universal vaccination coverage. Patients can be
vaccinated in a number of placesdoctors offices, employee health offices, walk-in clinics, and of
course pharmaciesand often, they dont remember when or where (or even if) they received an
immunization. Screening tools are needed so that health care professionals can offer immunizations at
every convenient opportunity. Moose Pharmacy, an independent, family owned and operated pharmacy
in rural North Carolina, implemented a comprehensive vaccine screening program. A report, published
in Journal of the American Pharmacists Association, includes key points to improve workflow.1
Moose Pharmacy is known for its provision of comprehensive patient care, allowing clinical pharmacists
and pharmacy residents to practice at the top of their licenses. The study was conducted at Moose
Pharmacys 5 dispensing pharmacy locations that fill from 750 to 2800 prescriptions each week. Clinical
pharmacists developed a vaccine screening tool and documentation form, modeling it on
recommendations from the CDC. They addressed all immunizations that North Carolina allows to be
administered by pharmacists. Pharmacy team members used the screening tool to identify adult patients
who had entered the pharmacy and needed vaccinations. Pharmacists offered needed immunizations
when the screening tool successfully identified a patient who was not fully up to date with their
recommended immunizations. If the patient agreed, he or she received the immunization. If not, the
pharmacist documented the reason for the refusal.
During the 30-day study period, staff (usually technicians, who assumed leading roles in this effort)
screened 631 patients. Most screenings occurred during data entry, although a minority were competed
at fill stations, prescription verification, or during clinical consultation. Pharmacists administered 11
influenza, 5 pneumococcal conjugate, 1 pneumococcal polysaccharide, 5 Tdap, and 6 zoster vaccines.
This represents a 7-fold increase in vaccination for these pharmacies compared to the same month in the
previous year. The researchers concluded that pharmacist-driven recommendations have the capability
to increase vaccination rates 200-fold.
26

Reference
Rhodes LA, Branham AR, Dalton ER, et al. Implementation of a vaccine screening program at an
independent community pharmacy. J Am Pharm Assoc. 2016; 1-7.
Fatal French clinical trial failed to check data before raising drug dose
James Randerson
22 December 2016
http://www.nature.com/news/fatal-french-clinical-trial-failed-to-check-data-before-raising-drug-dose1.21190
Criticism of the drug company at the centre of a disastrous clinical trial that left one participant dead and
four with long-term neurological symptoms has intensified following a revelation that the firm did not
use certain data when deciding to administer a higher dose that proved deadly. On 15 December, during
a conference presentation by a scientist from the Portuguese company, Bial, it emerged that the firm did
not use certain readings, called pharmacodynamic (PD) data, on how the drug BIA 10-2474 was acting
in participants who had received a lower dose, before taking the decision to increase the dosage.
This was a revelation as far as we are concerned, says David Webb, president of the British
Pharmacological Society (BPS), which hosted the conference in London. The trial, which was carried
out in Rennes, France, took a tragic turn in January. Helena Gama, head of Bials pharmacovigilance
and drug safety office, spoke for the company at the BPS meeting. When asked why the company had
not included the PD data in its dose-escalation decision, she said: The evaluation before starting a new
drug escalation is based on safety evaluation and pharmacokinetic data referring to other data on
how the drug is absorbed, distributed, metabolized and excreted by the body. We did not have any
profile that precluded the path to the further dosage. Bial was not legally required to use PD data, and
its trial protocol had been signed off by Frances medical regulator, the National Agency for the Safety
of Medicines and Health Products (ANSM). But experts in pharmacology and clinical-trial design say
that the company should have included these readings. Without the PD data, they were flying blind.
Thats when accidents happen, says Webb. I think that was negligent. Catherine Hill, a biostatistician
who previously served on the ANSMs scientific advisory board, is also surprised that Bial did not take
PD data. This seems incredible, she says. Flying blind is a perfect image. It is best practice to use
PD data, although not every trial does, notes Munir Pirmohamed, a molecular and clinical
pharmacologist at the University of Liverpool, UK.
First in humans
The Bial trial was the first to test BIA 10-2474 in humans. It was designed to explore whether the drug,
which had already been tested in mice, dogs, monkeys and rats, is safe to use in people. In particular,
says Webb, it was important to collect PD data because BIA 10-2474 is relatively unselective, meaning
that it could have effects in addition to its intended target in the body.
The drug binds an enzyme called fatty acid amide hydrolase (FAAH) an activity that might make it
effective at treating anxiety and motor disorders associated with Parkinsons disease, as well as chronic
pain in people with conditions such as cancer. PD data can reveal when the copies of the enzyme in the
brain are close to being saturated with the drug, a point at which levels of free-floating drug may rise
steeply with increasing dose, and potentially lead to unexpected off-target effects on other enzymes.
27

Critics at the BPS meeting suspect that because the company was not including PD data in its decision to
up the dose, it did not realize that FAAH was already saturated. But Bial does not accept this
conclusion. All official reports about the trial were inconclusive and all have considered this event as
unpredictable, and that there was no indication whatsoever, including in the pre-trials, that could have
predicted this outcome, said a company spokesperson. Both French authorities and the European
Medicines Agency in London have published updated guidance on first-in-human clinical trials since the
tragedy. And a separate report by the ANSM made six recommendations to improve the conduct of
future trials.
Memory loss
Gama also released new data on four trial participants who survived but became ill: she said that they
had not yet recovered from neurological symptoms including memory loss, headaches, motor disorders
and tremors. She also listed ten instances of neurological side effects, including dizziness and blurred
vision, in other volunteers who were given lower doses of the drug, although she stressed that these were
mild and transient. The long-term impact on the health of the more severely affected volunteers had not
been clear previously, but the fact that they are still experiencing symptoms underlines the conclusion
that the fatal reaction to the drug was not a one-off, says Webb. Thats the first time we know they are
not well that they are still damaged in some way. Since the trial, Bial has come under intense
pressure from the scientific community to release all data relating to the trial and pre-clinical work. The
BPS presentation revealed some such data, but calls for transparency are intensifying.
Isnt it time that this whole amount of data is released officially so that we can all have a discussion
about it? asked Adam Cohen, a clinical pharmacologist at Leiden University in the Netherlands, and
editor-in-chief of the British Journal of Clinical Pharmacology. In particular, he says, the company
should release its investigators brochure, the dossier of pre-clinical work on the drug, plus the full
human data from the trial itself. When quizzed by Cohen and Webb on why the company has still not
released the data 11 months after the fatal trial, Gama refused to make a specific commitment to release
them. But she added: We dont have any issue regarding releasing data to the scientific community.
1 Patient, 7 Tumors and 100 Billion Cells Equal 1 Striking Recovery
Source: New York Times
Author: DENISE GRADY
Date: DEC. 7, 2016
URL: http://www.nytimes.com/2016/12/07/health/cancer-immunotherapy.html
The remarkable recovery of a woman with advanced colon cancer, after treatment with cells from her
own immune system, may lead to new options for thousands of other patients with colon or pancreatic
cancer, researchers are reporting. Her treatment was the first to successfully target a common cancer
mutation that scientists have tried to attack for decades. Until now, that mutation has been bulletproof,
so resistant to every attempt at treatment that scientists have described it as undruggable. An article
about the case, from a team led by Dr. Steven A. Rosenberg, chief of surgery at the National Cancer
Institute, was published on Wednesday in The New England Journal of Medicine. The patient, Celine
Ryan, 50, an engineer, database programmer and the mother of five, has an unusual genetic makeup that
allowed the treatment to work. She is now cancer-free, though not considered cured. The treatment was
a form of immunotherapy, which enlists a patients immune system to fight disease. The field is
revolutionizing cancer treatment.
28

An experiment on one patient cannot determine whether a treatment will be effective in others, but
doctors said the results had the potential to help more people. It has huge implications, Dr. Carl H.
June, from the University of Pennsylvania, said in an interview. He was not part of the study, but wrote
an editorial accompanying it in the journal. Dr. June said the research was the first successful targeting
of a defect in a gene called KRAS, and is important because mutations in the gene are so common.
Every single pancreatic cancer patient has KRAS, Dr. June said, adding that the pharmaceutical
industry has spent billions trying unsuccessfully to target KRAS.
Still, he said, the big question is whether this case is one in a million, or something that can be
replicated and built upon?
About 53,000 cases of pancreatic cancer are expected in the United States this year, and nearly 42,000
deaths. It is one of the deadliest cancers; fewer than 10 percent of patients survive five years.
Worldwide, it killed about 330,000 people in 2012, the most recent year with global statistics available.
From 30 to 50 percent of colorectal cancers have KRAS mutations, too, and about 13 percent have the
same mutation that Ms. Ryan has. In the United States, about 95,000 cases of colon cancer and 39,000
cases of rectal cancer are expected in 2016, and 49,000 deaths from the two forms combined. Globally,
there were 1.4 million cases and 694,000 deaths in 2012.
The new discovery might not have been made at least, not now without Ms. Ryans persistence.
Researchers twice denied her request to enter the clinical trial, saying her tumors were not large enough,
she said. But she refused to give up and was finally let in.
The research involves cancer-fighting immune cells called tumor-infiltrating lymphocytes, or TILs.
These are white blood cells that swarm around tumors, a sign that the immune system is trying to attack
the cancer. Dr. Rosenberg has been studying TILs for decades, with the goal of enhancing their ability to
fight the disease and using them as a treatment. An attempt to treat another patient with tumors much
like Ms. Ryans did not work, almost certainly because the researchers could not produce enough highly
targeted TILs, Dr. Rosenberg said. So far, the cells have worked best against advanced melanoma, a
deadly form of skin cancer. By extracting TILs from tumors, multiplying them in the lab and then
returning them to the patient, Dr. Rosenbergs team has produced long remissions in 20 to 25 percent of
patients with that disease.
More recently, the team has focused on an even tougher problem: tumors in the digestive system,
including the colon and pancreas, and in ovaries, breasts and other organs, which cause more than 80
percent of the 596,000 cancer deaths in the United States each year.
The researchers analyze tumors for mutations genetic flaws that set the cancer cells apart from
normal ones. They also study TILs, looking for immune cells that can recognize mutations and therefore
attack cancerous cells but leave healthy ones alone. Ms. Ryan, from Rochester Hills, Mich., had colon
cancer that spread to her lungs despite surgery, chemotherapy and radiation. With few options, she
began looking into research programs and came across the TILs research at the National Cancer
Institute. In December 2014, she called the institute, hoping to join the study. But she was told, based on
her scans and records, that she did not have a tumor big enough to yield TILs. A research nurse
suggested she send her next set of scans; maybe, in the interim, the tumors would grow. Ms. Ryan took
that advice and was devastated to be turned down again.

29

I felt sure Id get in, Ms. Ryan said. My heart sank.

The rejection left her sobbing. But then she and her husband pulled up images of her scans on their
home computer, took screen shots and measurements of a lung tumor that seemed to match the study
criteria, and sent them to the cancer institute. She included a polite note asking that, if her tumor was not
eligible, she be told why. I was trying not to sound like a desperate maniac, but I was a desperate
maniac, she said. In March 2015, she got in. Whether the screen shots were a deciding factor is not
clear. Dr. Rosenberg said the team had been watching her progress and brought her in as soon as they
identified operable tumors.
SEE SAMPLE PRIVACY POLICY
A month later, the researchers performed surgery, removing several lung tumors to search for TILs. Ms.
Ryans tissue turned out to be a medical gold mine. She had a KRAS mutation and her TILs included
killer T-cells that locked onto the mutation like guided missiles. Her T-cells were able to recognize the
mutation because she has an uncommon tissue type, which is a genetically determined trait. As a result,
she carries a certain protein on the surface of her cells that plays an essential role in displaying the
KRAS mutation so that cancer-killing cells can find it and attack. Best of all, from a scientific
standpoint, was that Ms. Ryans KRAS mutation is shared by many other patients with colon and
pancreatic cancers. Those who share her tissue type may also be good candidates for treatment with
TILs. Researchers say they now have a blueprint that may enable them to develop cell treatments for
other patients as well. The killer T-cells have surface molecules called receptors that lock onto mutated
cells, and it may be possible to genetically engineer patients T-cells to give them those receptors and
their cancer-targeting ability.
To treat Ms. Ryan, the team selected a culture of TILs with high levels of immune cells that specifically
attacked her mutation. They multiplied those cells in the laboratory to produce huge numbers. Ms. Ryan
was first given chemotherapy to wipe out most of her white blood cells and allow the TILs to flourish.
Then, more than 100 billion TILs were dripped into her bloodstream through an intravenous line; it took
about 20 minutes, she said. About 75 percent were the killer T-cells that targeted her mutation. She was
also given interleukin-2, a substance that stimulates killer T-cells. Before being treated, Ms. Ryan had
seven tumors in her lungs. Over the next nine months, six shrank and then disappeared. The seventh
shrank at first, but then progressed. To remove it, surgeons took out the lower lobe of her left lung. Tests
of the excised tumor explained why it had resisted treatment: It had mutated and no longer carried the
tissue-type marker that had enabled the T-cells to attack it.
The tumors ability to escape the T-cells reveals a potential weak spot in the approach of targeting a
single mutation, said Dr. Drew M. Pardoll, the director of the Bloomberg-Kimmel Institute for Cancer
Immunotherapy at the Johns Hopkins University School of Medicine. Calling cancer versatile, he said,
The tumor always seems to come up with a workaround.
Even so, he said the research was a real and solid step forward.
Today, Ms. Ryan has no signs of cancer.
I feel great, she said.
But recently, two friends died of colon cancer, she said, adding, I so hope they can get this treatment to
everybody who needs it, and that it works.

30

Just One Dose of This Psychedelic Drug Can Ease Anxiety

Source: Time
Author: Alexandra Sifferlin
Date: Dec. 1, 2016
URL: http://time.com/4586333/psilocybin-cancer-anxiety-depression/
Two new trials show the powerful effects of magic mushrooms on cancer-related anxiety and depression
Cancer is a brutal disease on both the body and mind. Not only do treatments like chemotherapy take a
massive toll, but the emotional side effects can be hard to bear. Depression and anxiety are high among
people with cancer, including those in remission. But two new studies offer promising relief through an
unlikely source: hallucinogenic drugs.
In two new studies released simultaneously by researchers at New York University and Johns Hopkins,
doctors reveal that a single dose of psilocybina compound from magic mushroomscan ease anxiety
and depression for up to six months. The results have great potential for people dealing with the fear
associated with a cancer diagnosis, but also for people with psychiatric disorders that havent responded
to traditional treatments like psychotherapy or antidepressants.
Could Psychedelic Drugs Treat Mental Illness?
Scientists are experimenting with whether magic mushrooms could treat depression
The studies, both published in the Journal of Psychopharmacology, are accompanied by 11 editorials of
support from leaders in psychiatry, including two past presidents of the American Psychiatric
Association. Our results represent the strongest evidence to date of a clinical benefit from psilocybin
therapy, with the potential to transform care for patients with cancer-related psychological distress,
says NYU study author Dr. Stephen Ross, director of substance abuse services in the Department of
Psychiatry at NYU Langone in a statement.
The NYU Langone Medical Center study involved 29 people who had serious psychological distress,
like anxiety or depression, stemming from advanced cancer. (Some were in remission.) Each person
received either a capsule of psilocybin or a placebo capsule; in a second session, they were given the pill
they hadnt yet taken. The sessions lasted from four to six hours in a room equipped with music to listen
to, a couch and a sleep mask. People had their own individual experiences with the drug. But the results
were remarkable: 60-80% of people in the study reported reductions in their depression and anxiety
symptoms that lasted six months after the treatment.
The Johns Hopkins study, which involved 51 adults, had similar results. They each received one large
dose of the drug, and six months later, 80% of the people in the trial continued to show decreases in
depression and anxiety symptoms. Eighty-three percent of people reported increases in their well-being
and life satisfaction, and 67% said the trial was one of the top five most meaningful experiences in their
lives. Several people described experiencing an overwhelming feeling of love while on the drug and felt
they had changed immediately. The feeling of immense love lingered for weeks, and four years later I
still feel it at times, says participant Dinah Bazer, who was experiencing severe anxiety about a
possible ovarian cancer recurrence. My fear and anxiety were completely removed, and they havent
come back. (You can read more about Bazers experience in her personal essay here). Lisa Callaghans
late husband, former TV news director Patrick Mettes, was also in the NYU trial. Mettes eventually died
from cancer of the bile ducts, but undergoing the trial gave him a sense of peace, says his wife. In his
31

trip there was an evolution through all of these stages of emotional development, says Callaghan. He
was reborn into this place of personal and universal love. He said he felt it all around him, and he felt a
sense of forgiveness too.
The potential therapeutic use of psilocybin has been recognized for years, but strict drug laws
implemented 45 years ago stalled research. In the 1950s and 1960s, several teams in the United States
studied psychedelic compounds for potential mental disorder treatments. But widespread recreational
use of the substances became cause for concern and overshadowed the possible therapeutic benefits. In
1971, psilocybin and other psychedelic compounds were classified as schedule 1 drugs, meaning that the
government believes they have high potential for abuse. This classification makes it very difficult for
research to continue, despite the fact that experts argue adverse side effects from psilocybin (when used
responsibly) are rare.
I tried to understand how something this big had been buried, says Ross. Due to these restrictions,
Ross says it took the hospital a couple years to get their study off the ground. Some of the men and
women in the studies did experience side effects, like nausea and headaches, but none were severe. Its
unclear precisely how psilocybin works, but the study authors say that the drug may activate parts of the
brain that are impacted by serotonin, which can play a role in anxiety, mood and depression.
Significantly more research is needed before psilocybin could be considered as a clinical therapy. The
researchers stress that psilocybin in the trials was given in a very controlled environment with multiple
investigators present, and that people should not attempt the drug on their own. Theres also some
concern that pharmaceutical companies may not see financial incentives in single-dose therapies.
Still, many people in the medical community are hopeful. Were excited about finding a medicine that
can be helpful to people suffering from conditions not successfully treated by standard treatment, says
Dr. George Greer, medical director of the Heffter Research Institute, which helped fund the studies.
Theres a lot of interest.
The New Bottom Line on Your Daily Aspirin
Source: Time
Author: Alice Park
Date: Dec. 1, 2016
URL: http://time.com/4586868/daily-aspirin-heart-attacks/
Experts are divided over whether daily aspirin for healthy people is a good thing; the latest study
attempts to clarify the confusion Aspirin can be a life saver; it can reduce the risk of further heart attacks
in people who have already had one and lower the risk of certain cancers. That encouraging data led
people to ask if the over-the-counter drug could also help prevent heart problems and cancer in the first
place. In the latest study on the subject, published in the journal PLOS ONE, researchers led by Dr.
David Agus at the University of Southern California Keck School of Medicine report that for older
people, daily aspirin can lower the risk of heart attack and some cancers while leading to a longer life.
The model for the study is based on national databases about various health factors, from cancer
incidence to rates of other chronic diseases, as well as body mass index and how functional people
remain as they get older. The model also incorporates costs of health care for an aging population, and
found that broader use of aspirin could save hundreds of thousands of lives and $692 billion in health
care costs.

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The results are the latest in the debate over whether aspirin should be used in healthy people to prevent a
first heart attack, stroke, cancer or other health problem. Because aspirin helped prevent second heart
attacks in people with heart disease, at first doctors recommended that those at high risk for heart
problems start taking a low dose of aspirin every day. (At 80mg, that dose was much lower than the
pain-killing doses that are typically three to four times higher.) Aspirin is a powerful anti-inflammatory
agent, and researchers believe it can reduce the inflammation that can trigger heart attacks. In the case of
cancer, the inflammation can cause damage that promotes abnormal cells like tumors to grow.
But in 2014, the Food and Drug Administration (FDA) deemed that such preventive doses in otherwise
healthy people produced more risk than benefit. Aspirin, which works to reduce inflammation, activates
enzymes that can irritate stomach and intestinal tissues, causing ulcers and bleeding. For people who
havent yet had a heart attack, therefore, the FDA determined that the risk of such side effects were too
great compared to the potential benefit they might get. The American Heart Association (AHA) and the
U.S. Preventive Services Task Force (USPSTF), a government-appointed panel of experts that studies
large health questions, also have concerns about the drugs side effects.
But they continue to recommend the medication for a specific group of people who have not yet had a
heart attack but who are at higher risk for one. They call for calculating an individuals specific risk of
developing heart disease in the next 10 years, based on a number of factors including their age, family
history of heart trouble, blood pressure and cholesterol levels.
Despite that advice, however, 40% of men and 10% of women who fit those criteria and should be
taking aspirin are not, according to the latest study. The authors also predict that if everyone who meets
the conditions would take the drug as recommended, an estimated 900,000 more people would be alive
by 2036. Thats because for every 1,000 people, 11 cases of heart disease and four cases of cancer
would be averted.
So should everyone over age 50 start taking daily low-dose aspirin in order to live longer?
Agus and his team also predicted what would happen under this scenario. The benefits of the drug have
to be weighed against the fact that people who may avoid heart disease and add more years to their lives
may also be more likely to develop cancer, diabetes or a disease of aging. The side effects of intestinal
bleeding also have to be considered. Still, Agus argues that at the very least, people who currently meet
recommended criteria for taking aspirinincluding those who are at higher risk of heart problems
should be taking the medication. No matter how you look at it, the benefits are there. With [everyone
taking it] the results are tempered, because other diseases happen, but clearly there is still benefit. The
findings should push more people toward the AHA and USPSTF advice, which calls for people to
discuss with their doctor their individual risk and benefit ratio, rather than deciding that aspirin is or isnt
right for them based on the drugs label. We cant tell everybody over 50 what they should do, says
Agus. The role of the physician is to explain risk and benefit and together with the patient make a
decision.

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Have you talked to your family about organ donation?

Source: New Scientist
Author: Justin Mullins
Date: 30 November 2016
URL: https://www.newscientist.com/article/mg23231021-300-have-you-talked-to-your-family-aboutorgan-donation/
IF YOU or one of your children needed a heart transplant, your gratitude to the family that donated one
would be boundless. In their hour of greatest despair that family would have consented to an organ
donation, a selfless, life-saving choice. But if the positions were reversed, could you make the same
decision? Sadly, the number of donor hearts does not match demand. That means many adults and
children die waiting. Every death is the loss of a father or a son, a mother or a daughter. Part of the
problem is that not enough families give their consent. In the UK only 60 per cent agree compared with
80 per cent in many other European countries. That means 4 out of 10 families who are approached in
the UK refuse to donate.
Perhaps thats not surprising. Many people are uncomfortable about confronting their mortality and that
of their immediate family. Surveys for the National Health Service show that more than 30 per cent of
people have never discussed organ donation, and few are aware how those closest to them feel about it.
The NHS wants to change this. Its organ donation team is encouraging families to talk about organ
donation, to think about how they would feel about donation if they needed a transplant and to
encourage them to sign the organ donation register at organdonation.nhs.uk. And of course, the problem
is not confined to hearts. People waiting for lungs, livers, kidneys, corneas and so on, vastly outnumber
the supply of organs for transplant. At the end of March 2016, there were almost 6500 patients waiting
for some kind of transplant. Even a small increase in the percentage of people agreeing to donate would
make a huge difference to the waiting time. Increasing the UK consent rate from 60 per cent to 80 per
cent would lead to about 1000 more transplants each year. Thats a great many lives. One of them could
be yours.
Chantix (varenicline) and Zyban (bupropion): Drug Safety Communication - Mental Health Side
Effects Revised
December 16, 2016
Source:
https://www.drugs.com/fda/chantix-varenicline-zyban-bupropion-safety-communicationmental-health-revised-13952.html
Based on an FDA review of a large clinical trial that FDA required the drug companies to conduct, FDA
determined the risk of serious side effects on mood, behavior, or thinking with the stop-smoking
medicines Chantix (varenicline) and Zyban (bupropion) is lower than previously suspected. The risk of
these mental health side effects is still present, especially in those currently being treated for mental
illnesses such as depression, anxiety disorders, or schizophrenia, or who have been treated for mental
illnesses in the past. However, most people who had these side effects did not have serious
consequences such as hospitalization. The results of the trial confirm that the benefits of stopping
smoking outweigh the risks of these medicines. See the Drug Safety Communication for a data
summary.

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As a result of the large clinical trial review, FDA is removing the Boxed Warning, FDAs most
prominent warning, for serious mental health side effects from the Chantix drug label. The language
describing the serious mental health side effects seen in patients quitting smoking will also be removed
from the Boxed Warning in the Zyban label. FDA is also updating the existing warning section in both
labels that describes the side effects on mood, behavior, or thinking to include the results from the
clinical trial. This decision is consistent with the recommendations of external experts at a September
2016 FDA Advisory Committee meeting. The patient Medication Guide that explains the risks
associated with the use of the medicines will continue to be provided with every patient prescription;
however, the risk evaluation and mitigation strategy (REMS) that formally required the Medication
Guide will be removed.
BACKGROUND: FDA review of the clinical trial results also confirmed that Chantix, Zyban, and
nicotine replacement patches were all more effective for helping people quit smoking than was an
inactive treatment called a placebo. These medicines were found to better help people quit smoking
regardless of whether or not they had a history of mental illness. RECOMMENDATION: Health care
professionals should counsel patients about the benefits of stopping smoking and how they can get help
to quit, and discuss the benefits and risks of using medicines to help them quit smoking.
Patients should stop taking Chantix or Zyban and call their health care professionals right away if they
notice any side effects on mood, behavior, or thinking. Patients should also talk to their health care
professionals for help and information about stopping smoking, including about whether stop-smoking
medicines may help or if they have any questions or concerns about taking a medicine (See Related
Information for more quit smoking resources). Healthcare professionals and patients are encouraged to
report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety
Information and Adverse Event Reporting Program: Complete and submit the report Online:
www.fda.gov/MedWatch/report
FDA expands indication for continuous glucose monitoring system, first to replace fingerstick
testing for diabetes treatment decisions
December 20, 2016
Source: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm534056.htm
The U.S. Food and Drug Administration today expanded the approved use of Dexcoms G5 Mobile
Continuous Glucose Monitoring System to allow for replacement of fingerstick blood glucose (sugar)
testing for diabetes treatment decisions in people 2 years of age and older with diabetes. This is the first
FDA-approved continuous glucose monitoring system that can be used to make diabetes treatment
decisions without confirmation with a traditional fingerstick test. The system was previously approved
to complement, not replace, fingerstick testing for diabetes treatment decisions.

"The FDA works hard to help ensure that novel technologies, which can reduce the burden of daily
disease management, are safe and accurate," said Alberto Gutierrez, Ph.D., director of the Office of In
Vitro Diagnostics and Radiological Health in the FDAs Center for Devices and Radiological Health.
"Although this system still requires calibration with two daily fingersticks, it eliminates the need for any
additional fingerstick blood glucose testing in order to make treatment decisions. This may allow some
patients to manage their disease more comfortably and may encourage them to have routine dialogue
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with their health care providers about the use of real-time continuous glucose monitoring in diabetes
management."
Because the bodys ability to control blood sugar levels is impaired in people with diabetes, patients
must regularly test and monitor their blood sugar. This is traditionally done multiple times per day by
taking a blood sample from the fingertip (known as a "fingerstick" sample) and testing it with a blood
glucose meter. Results indicate if glucose levels are too high (hyperglycemia) or too low
(hypoglycemia), helping patients and their health care providers make appropriate diabetes management
decisions. The G5 Mobile Continuous Glucose Monitoring System uses a small sensor wire inserted just
below the skin that continuously measures and monitors glucose levels. Real-time results are sent
wirelessly every five minutes to a dedicated receiver and a compatible mobile device (e.g., smart phone
or tablet) running a mobile app. Alarms and alerts indicate glucose levels above or below user-set
thresholds. The system measures glucose in fluid under the skin and must be calibrated at least two
times per day using blood obtained from fingerstick tests. However, additional daily fingerstick blood
tests are generally no longer necessary because unlike other continuous glucose monitoring systems,
results from this device can now be used directly by patients to make diabetes treatment decisions
without confirmation from a traditional fingerstick test.
According to the U.S. Centers for Disease Control and Prevention, more than 29 million people in the
U.S. have diabetes. People with diabetes either dont make enough insulin (type 1 diabetes) or cant use
insulin properly (type 2 diabetes). When the body doesnt have enough insulin or cant use it effectively,
blood sugar builds up in the blood. High blood sugar levels can lead to heart disease; stroke; blindness;
kidney failure; and amputation of toes, feet or legs. The FDA evaluated data from two clinical studies of
the G5 Mobile Continuous Glucose Monitoring System. These studies included 130 adults and children
aged 2 years and older with diabetes. All studies included a seven-day period where system readings
were compared to blood glucose meter values, as well as to a laboratory test method that measures
glucose values. No serious adverse events were reported during the studies. Risks associated with use of
the system may include hypoglycemia or hyperglycemia in cases where information provided by the
device is inaccurate and used to make treatment decisions or where hardware or set-up issues disable
alarms and alerts, as well as skin irritation or redness around the devices adhesive patch. Users are
warned that the system must be calibrated using a fingerstick blood sample at least once every 12 hours
and that taking any medications containing acetaminophen while wearing the system may falsely raise
glucose readings.
The G5 Mobile Continuous Glucose Monitoring System is manufactured by Dexcom, Inc., located in
San Diego, California. The FDA, an agency within the U.S. Department of Health and Human Services,
promotes and protects the public health by, among other things, assuring the safety, effectiveness, and
security of human and veterinary drugs, vaccines and other biological products for human use, and
medical devices. The agency also is responsible for the safety and security of our nations food supply,
cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco
products.

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FDA grants accelerated approval to new treatment for advanced ovarian cancer
December 19, 2016
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm533873.htm
The U.S. Food and Drug Administration today granted accelerated approval to Rubraca (rucaparib) to
treat women with a certain type of ovarian cancer. Rubraca is approved for women with advanced
ovarian cancer who have been treated with two or more chemotherapies and whose tumors have a
specific gene mutation (deleterious BRCA) as identified by an FDA-approved companion diagnostic
test.
Todays approval is another example of the trend we are seeing in developing targeted agents to treat
cancers caused by specific mutations in a patients genes, said Richard Pazdur, M.D., director of the
Office of Hematology and Oncology Products in the FDAs Center for Drug Evaluation and Research
and acting director of the FDAs Oncology Center of Excellence. Women with these gene
abnormalities who have tried at least two chemotherapy treatments for their ovarian cancer now have an
additional treatment option. The National Cancer Institute estimates that 22,280 women will be
diagnosed with ovarian cancer in 2016 and an estimated 14,240 will die of this disease. Approximately
15 to 20 percent of patients with ovarian cancer have a BRCA gene mutation.
BRCA genes are involved with repairing damaged DNA and normally work to prevent tumor
development. However, mutations of these genes may lead to certain cancers, including ovarian cancers.
Rubraca is a poly ADP-ribose polymerase (PARP) inhibitor that blocks an enzyme involved in repairing
damaged DNA. By blocking this enzyme, DNA inside the cancerous cells with damaged BRCA genes
may be less likely to be repaired, leading to cell death and possibly a slow-down or stoppage of tumor
growth.
Today, the FDA also approved the FoundationFocus CDxBRCA companion diagnostic for use with
Rubraca, which is the first next-generation-sequencing (NGS)-based companion diagnostic approved by
the agency. The NGS test detects the presence of deleterious BRCA gene mutations in the tumor tissue
of ovarian cancer patients. If one or more of the mutations are detected, the patient may be eligible for
treatment with Rubraca.
The safety and efficacy of Rubraca were studied in two, single-arm clinical trials involving 106
participants with BRCA-mutated advanced ovarian cancer who had been treated with two or more
chemotherapy regimens. BRCA gene mutations were confirmed in 96 percent of tested trial participants
with available tumor tissue using the FoundationFocus CDxBRCA companion diagnostic. The trials
measured the percentage of participants who experienced complete or partial shrinkage of their tumors
(overall response rate). Fifty-four percent of the participants who received Rubraca in the trials
experienced complete or partial shrinkage of their tumors lasting a median of 9.2 months.

Common side effects of Rubraca include nausea, fatigue, vomiting, low levels of red blood cells
(anemia), abdominal pain, unusual taste sensation (dysgeusia), constipation, decreased appetite,
diarrhea, low levels of blood platelets (thrombocytopenia) and trouble breathing (dyspnea). Rubraca is
associated with serious risks, such as bone marrow problems (myelodysplastic syndrome), a type of
cancer of the blood called acute myeloid leukemia and fetal harm.
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The agency approved Rubraca under its accelerated approval program, which allows approval of a drug
to treat a serious or life-threatening disease or condition based on clinical data showing the drug has an
effect on a surrogate (substitute) endpoint that is reasonably likely to predict clinical benefit. The
sponsor is continuing to study this drug in patients with advanced ovarian cancer who have BRCA gene
mutations and in patients with other types of ovarian cancer. The FDA also granted the Rubraca
application breakthrough therapy designation and priority review status. Rubraca also received orphan
drug designation, which provides incentives such as tax credits, user fee waivers and eligibility for
exclusivity to assist and encourage the development of drugs intended to treat rare diseases.
Rubraca is marketed by Clovis Oncology, Inc. based in Boulder, Colorado. The FoundationFocus
CDxBRCA companion diagnostic is marketed by Foundation Medicine, Inc. of Cambridge,
Massachusetts. The FDA, an agency within the U.S. Department of Health and Human Services,
protects the public health by assuring the safety, effectiveness, and security of human and veterinary
drugs, vaccines and other biological products for human use, and medical devices. The agency also is
responsible for the safety and security of our nations food supply, cosmetics, dietary supplements,
products that give off electronic radiation, and for regulating tobacco products.

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