The following are statements from 10 pharmaceutical companies who responded to the

9Wants to Know questions regarding the twelve Orphan Drugs we identified in our
investigation. Two companies Knight Therapeutics, maker of Impavido, and Arbor
Pharma, maker of Horizant did not respond to repeated requests for comment.
ABBVIE STATEMENT REGARDING HUMIRA
Humira has multiple orphan drug designations and approvals for the treatment of diseases
including juvenile arthritis, juvenile Chrons, Hurley stages 2 and 3 and more. The latest of
those designations will ensure market exclusivity until 2023. Humira has more than doubled
in price since 2012 according to Centers for Medicare and Medicaid data. The following are
comments provided to 9Wants to Know from AbbVie:

The Orphan Drug Designation program was created by the U.S. Congress and administered by
the FDAs Office of Orphan Product Development (OOPD) in order to spur innovation and
development of medicines to treat rare diseases. AbbVies research and development efforts are
focused on areas with significant unmet medical need.
An example of this is our work with HUMIRA in chronic inflammatory diseases. HUMIRA was
the first fully-human biologic and AbbVie continues to invest in the continued development of
new indications and enhancements for patients with unmet medical need. AbbVie's innovation
with HUMIRA has resulted in an unprecedented 10 FDA-approved indications, four of which
have received orphan drug designation, including juvenile arthritis, pediatric Crohns disease,
hidradenitis suppurativa and non-infectious pan, posterior and intermediate uveitis.=

OTSUKA AMERICA PHARMACEUTICALS

Abilify from Otsuka is approved as an orphan drug to treat Tourettes syndrome. It is also
FDA approved for other indications and has increased in price by more than 54 percent since
2012. The following are statements from Otsuka America Pharmaceuticals relating to Abilify:
The Orphan Drug Act provides an incentive for pharmaceutical manufacturers to expend time,
money and other resources to develop medicines that can be approved to treat orphan diseases.
Due to the number of patients with these diseases, companies often overlook these diseases and
the incentive provided by the Orphan Drug Act to help encourage this research is solely the
extension of market exclusivity for the orphan indication.
Otsuka devoted additional resources to further research and develop ABILIFY (aripiprazole)
for an orphan indication, Tourettes Disorder, which had not had a newly approved medication
for many years, and received the extended, orphan indication exclusivity. Again, as applied by
the FDA, the Act extends exclusivity ONLY for the orphan indication, and not for all the
indications for which the drug may have approval.
As a result, the extended market exclusivity for the orphan indication did not prevent the entry
into the market of generic competitors to ABILIFY for its other non-orphan indications. Generic
versions of aripiprazole did enter the market in May 2015, resulting in substantial reduction in
ABILIFY sales.
Generic aripiprazole is available to patients, and physicians are free to prescribe generic
aripiprazole for their patients suffering from the orphan disease, even though the FDA has not
approved the generic version for that use.
Otsuka remains committed to and focused on developing new treatments for patients in areas of
high unmet medical need, and to ensuring appropriate access to treatments for those patients.

STATEMENT FROM GENENTECH REGARDING AVASTIN

Avastin is a popular cancer drug that received orphan drug approval for the treatment of
ovarian cancer in 2014. According to a 2016 report from Americas Health Insurance Plans,
Avastin cost more than $149,000 a year for cancer patients.

There is no correlation between orphan drug designations and the price of our medicines. We
take the pricing of our medicines very seriously and consider a variety of factors, including how
well the medicine works and the amount of money we need to allow us to continue discovering
new medicines for people with serious diseases such as cancer and blindness.

Each year, we invest nearly $10B (Source: Strategy&. "The Global Innovation 1000: Top 20 R&D
Spenders 2005-2016." more than any other healthcare company in the world - and we have
been highly productive with our research dollars, bringing 12 new medicines to patients in the
past 7 years. We also continue to invest in significant and sustained research for each of our
medicines after they first become available. We follow the science to determine how they might
help people with other diseases. For example, since Avastin was first approved in 2004, we have
continued to study the medicine and it is now approved for 9 distinct uses across 6 different
types of cancer. We have had more than 500 studies of Avastin ongoing at one time across
different diseases to determine how best to help people.

At times, we do raise the prices of some of our medicines. The money we generate allows us to
continue searching for cures. We consider the same factors that we do when setting the initial
price and do our best to make sure that any change in price does not prevent someone from
getting one of our medicines.

Genentech is committed to ensuring our medicines get to the people who need them, even if
they cant afford them. Over the past 20 years, Genentech has helped more than 1.5 million
patients get the medicines they need. In 2016 alone, we helped more than 166,000 people,
including by:

Providing free medicine to people who meet certain financial criteria and do not have
insurance, are underinsured or whose insurance wont cover a Genentech medicine.
Helping patients understand their insurance and providing assistance when a payer denies
coverage.
Providing assistance to eligible patients with their co-pay.

If any of your viewers need help with access to a Genentech medicine, we encourage them to call
(866) 4 ACCESS or visit Genentech-Access.com.

LUNDBECK ANSWERS REGARDING ONFI

Onfi, a drug used to treat seizures, has increased in price by 160 percent since 2012. It was not
approved in the United States until 2011, though clobazam was found to be effective against
treating seizures in 1978. The following are the questions 9Wants to Know sent to Lundbeck
and their answers to those questions:
Q: In what ways has Lundbeck helped make Onfi available for patients who need
it?
A: Lundbeck offers a variety of support programs for patients facing access issues with respect
to our products, including, but not limited to, certain copayment support and free product
programs for eligible patients.
Q: Why has Lundbeck continued to increase the price of Onfi?
A: Many factors go into our pricing. As you know, the most obvious and significant is the
substantial investment we make in researching and developing products. Our revenues must
cover expenses related to the R&D of products that make it to the market, as well as those that
fail to make it to the market. For instance, idalopirdine for Alzheimer's where we recently had
three failed Phase 3 trials and desmoteplase for stroke. Both were studied to address significant
unmet needs. In addition to funding R&D -- both successes and failures -- price adjustments are
made to keep pace with inflation and to continue to invest in our current and future products. In
the case of Onfi, we have made continuous investments to develop and bring forward enhanced
dosing formulations, including scored tablets and oral suspension alternatives. The feedback
from physicians and families has consistently indicated these formulations offer even greater
convenience and ease of administration for the LGS patient population which can be quite
difficult to dose and are often living with frequent, severe and debilitating seizures. Not only do
scored tablets add convenience in dosing, but it was also developed with access in mind since it
helps lessen the potential for multiple co-pays.
Q: Since clobazam was developed and has been in use since the 1970s -- in what
way is Onfi's orphan drug designation helping patients?
A: Lundbeck acquired the North American rights to clobazam in 2004 and invested in many
years of pre-clinical and clinical studies before obtaining FDA approval in 2011. For more than
30 years, clobazam was primarily used outside of the U.S. for other conditions besides LGS.
Lundbeck invested heavily in both Phase II and Phase III clinical studies to assess the safety and
efficacy of Onfi specifically for people with Lennox-Gastaut syndrome (LGS), which had not
been as extensively evaluated in earlier studies, nor had it been evaluated in children ages 2
years or older. This included the largest pivotal Phase III trial ever conducted in patients with
LGS. Given the very small size of the LGS population, it took substantially longer, and required
substantial investment, to recruit patients for these trials compared with more common disease
states.
Lennox-Gastaut Syndrome is a rare and severe epilepsy that starts in childhood and makes up
an estimated 1-2 percent of all epilepsies and thought to be just more than 30,000 in the U.S.
A drug is designated an orphan by the FDA if it treats a condition that impacts fewer than
200,000 people. The Orphan Drug Act was passed to stimulate the development of drugs for
rare diseases, and the orphan drug designation for Onfi made it possible for Lundbeck to bring
this important treatment to people in the U.S. in need of additional treatment options given the
intractable nature of this challenging seizure disorder.
Background on Lundbeck

Lundbeck is the only global pharmaceutical company solely focused on brain disorders,
one of the costliest and riskiest areas of medicine.
We are a research-driven organization that invests approximately 20 percent of our
annual revenue directly back into our R&D programs.
Lundbeck has a unique ownership structure. We are 70% owned by the Lundbeck
Foundation, which reinvests our profits (~$100M) each year in basic research and
another 1 million annually in the Brain Prize, an amount even greater than the Nobel
Prize.
Tufts Center data shows that drug development for brain disorders takes about 20%
longer, costs approximately $100M more, and fails at a higher rate than nearly any other
area of medicine. As such, many companies have greatly scaled back or abandoned their
research in CNS.

TAKEDA COMMENTS REGARDING COLCRYS

Colcrys was approved as an orphan drug for the treatment of familial Mediterranean fever,
but colchicine is more commonly used to treat gout. It is a very old drug. Some studies suggest
that colchicine was used in 550 AD for the treatment of gout. Modern studies date back to the
1880s. The FDA approved Colcrys as an orphan drug in 2009 and market exclusivity lasted 7
years, expiring in 2016. The following bullet points were sent to 9Wants to Know from Takeda.

It is important to note that Colcrys is not an orphan drug, nor covered by any orphan
drug program.

When the FDA launched its Unapproved Drugs Initiative in 2006, all marketers of
unapproved drugs, including all colchicines products, were notified that drugs on the
market had to comply with all current FDA requirements. URL Pharma was the only
manufacturer to accept the challenge of refining colchicine and conducting the necessary
clinical trials to gain FDA approval, and subsequent market exclusivity in 2009.

The clinical and development program undertaken for Colcrys by URL Pharma, clarified
important dosing, safety, efficacy and usage information compared to prior oral
colchicine formulations.

Takeda acquired URL Pharma, including the drug Colcrys, in 2012.

At Takeda, we believe all patients should have access to the medications prescribed by
their healthcare providers. We also understand that some patients may have financial
situations that make it difficult to pay for their prescriptions

We are committed to offering patient assistance programs and resources to address

patient needs and help ensure access to Takeda medicines.

For Colcrys, we offer several options:

o One option is the Colcrys co-pay assistance card with which eligible patients pay
no more than $15 per prescription.
o Patients can learn more about Takedas patient assistance programs by
visiting www.takedahelpathand.com or calling 1-800-830-9159.
STATEMENT FROM MALLINCKRODT REGARDING H.P. ACTHAR GEL
H.P. Acthar Gel was FDA approved in the 1950s and has been used to treat infantile spasms
for many years. However, it was not FDA approved for the treatment of infantile spasms until
2010, when Questor Pharma sought Orphan Drug Status for that use. Once designated as an
Orphan Drug and protected by market exclusivity, the price for a single vial of H.P. Acthar Gel
jumped from about $1,600 to more than $36,000 today, according to a study published by the
National Institutes of Health. Mallinckrodt now owns H.P. Acthar Gel; the following is a
statement from Mallinckrodt:
In August 2014, Mallinckrodt acquired H.P. Acthar Gel, a drug that has made and continues to
make a significant difference in the lives of very sick patients with unmet medical needs.
In 2010, the U.S. Food and Drug Administration approved Acthar for use in the treatment of
infantile spasms, and the drug was granted orphan drug status with respect to the treatment of
that condition. At that time, the FDA also conducted a full review of the Acthar label and
determined there was sufficient scientific and clinical evidence to support 19 indications for the
drug. Other than for infantile spasms, where Acthar has clinical evidence to support its
effectiveness and is considered the gold standard, the drug is typically prescribed as a third or
fourth line of treatment for patients when other treatment options, such as high-dose steroids,
have become ineffective or are no longer tolerated.
Since acquiring Acthar, Mallinckrodt has been committed to providing data to physicians to
inform their understanding of which patients will benefit the most from the drug. Overall the
company has invested more than $250 million in Acthar to modernize manufacturing and
secure the supply chain, and for work in product characterization, and clinical and health
economic studies including:

Three company-sponsored Phase 4 clinical trials for rheumatoid arthritis, systemic lupus
erythematosus, and focal segmental glomerulosclerosis.
Phase 2 proof-of-concept trial to study the efficacy of the drug in amyotrophic lateral
sclerosis (ALS), often called Lou Gehrigs disease, for which there are very few effective
treatment options available at present.
Several multiple sclerosis studies, underway or nearing initiation.
All told, more than 800 patients will be enrolled in these company-sponsored, randomized
controlled clinical trials to study Acthar. As publicly-stated, Mallinckrodt expects to further
increase its R&D spending in absolute dollars at least 50% by 2021, and to more than double
R&D spending over the next decade, with the vast majority of our spending taking place in the
United States.
Prior to its acquisition by Mallinckrodt, the list price of Acthar was approximately $32,000. The
current list price per vial for the drug is $36,382, not the higher numbers which have appeared
in various reports, and Mallinckrodt discounts this list price to both public and private payers.
Mallinckrodt takes our responsibility as a pharmaceutical manufacturer very seriously, and our
pledge on drug pricing and innovation describes our philosophy around responsible pricing. The
pledge can be found: http://www.mallinckrodt.com/corporate-responsibility.
STATEMENT FROM HORIZON PHARMA REGARDING PROCYSBI
Procysbi is a delayed release form of cysteamine, a drug which has been FDA approved in the
U.S. under the brand name Cystagon since 1994 and was developed in the 1970s. Procysbi
currently costs about $5,000 for 60 pills. The equivalent dose of Cystagon costs $45. The
following is a statement from Horizan Pharma:
Most importantly, Horizon Pharma invests its resources to ensure patients have access to its
innovative medicines the vast majority of PROCYSBI patients pay $0 per month. Our efforts
to provide access to our medicines for patients who need them are part of our overall approach
to business. in 2016, Horizon provided $1.5 billion in patient support.

Our investment to develop and make PROCYSBI available exemplify what the Orphan Drug Act
was created for: incentivizing the advancement of innovative medicines for underserved patient
populations there are less than 500 nephropathic cystinosis patients in the United
States. PROCYSBI was granted orphan drug exclusivity because its bioavailability and 12 hour
dosing schedule is a significant advance over immediate-release cysteamine, which required
strict, every 6 hour, around the clock dosing that forced patients and caregivers to interrupt
sleep in order to take their medicine these challenges can lead to lack of compliance, failure to
thrive, and serious, long-term, irreversible damage to organs and tissue. The development of
PROCYSBI was driven by the unmet needs vocalized by the nephropathic cystinosis patient
community, and the FDA recognized PROCYSBI as a significant advance for these patients by
awarding it orphan drug status.

PTC THERAPEUTICS ON EMFLAZA

Emflaza (deflazacort) was not FDA approved in the United States until 2017, though clinic
trials completed in 1995 demonstrated the efficacy of deflazacort in treating Duchenne
muscular dystrophy. Marathon Pharmaceuticals announced they intended to sell Emflaza for
$89,000 a year in February. After weeks of public backlash, Marathon sold Emflaza to PTC
Therapeutics, who has not yet release how it plans to price Emflaza. The following is a
statement from PTC Therapeutics:

Emflaza is the first FDA-approved, anti-inflammatory therapy for Duchenne Muscular

Dystrophy (DMD) patients 5 years and older, regardless of genetic mutation. This agreement to
acquire Emflaza continues our nearly 20 year partnership with the Duchenne community to
address the unmet medical need of this devastating disorder and to bring treatments to
fundamentally change the lives of those living with Duchenne. We understand that availability
and access are important for the community. It is critical that families can afford medicines
without negatively impacting their familys financial health. As we develop pricing and launch
plans for Emflaza, we will incorporate this and additional feedback from the Duchenne
community, patient advocacy organizations and other related stakeholders into the plan. We are
committed to making product availability a priority.
The Orphan Drug Act enables companies like PTC to focus on meeting the needs of
patients with rare diseases or conditions, over 90 percent of which, have no treatment available
to them today. DMD is one such condition with a small number of patients affected,
approximately 9,000 patients in the U.S., and a high unmet need.
DEPOMED ON GRALISE:

Depomed declined to provide a statement regarding Gralise and instead told 9Wants to Know
that Gralise falls outside the scope of your questions. Gralise is a form of gabapentin, which
was developed in the 1970s. Gralise is FDA approved to treat postherpetic neuralgia. The drug
has increased in price by more than 200 percent since 2012 according to CMS data. In follow-
up email, Depomed sent this:

As for pricing, Depomed has always exercised a balanced approach to all of our portfolio
products and works closely with patients, physicians, payors and insurers to ensure that patients
in need get the appropriate treatment.

STATEMENT FROM VALEANT REGARDING XENAZINE

Xenazine was not approved in the U.S. until 2008, though early studies of tetrabenazine
showed it was able to surpress involuntary movements in 1972. It lost exclusivity in 2015, but
continues to cost more than $6,500 per a monthly dose when patients used to be able to import
the same dose for less than $45 per month. The following is a statement from Valeant on
Xenazine:
Xenazine does not have current Orphan Drug exclusivity status and there are generic alternative
competitor products on the market. In 2016, Valeant created a Patient Access and Pricing
Committee that takes an approach that reflects the Companys commitment to ensuring that
appropriate pricing practices are met and that the investments we make in our R&D pipeline
continue to result in innovative products that improve people's lives.