PRODUCT X Profile

Indications

Product X is indicated in patients 16 years and older with partial onset seizures (POS) as adjunctive
therapy with or without secondary generalization

Mechanism
of action

Binding to synaptic vesicle proteins in the brain is considered to be the primary mechanism for Product X
anticonvulsant activity, however, the precise mechanism by which Product X exerts its anticonvulsant
activity has not been fully elucidated

Formulations

Dosing
Instructions

Administration
Instructions
Elimination
Contraindications

Oral Tablets (film-coated tablets)

Other presentations include:
Vial containing 10mg/ml solution for injection which may be used when oral administration is
temporarily not feasible
10 mg/ml oral solution
Initial dose of Product X is twice daily
No up-titration required, therapeutic dose achieved rapidly

May be taken with or without food

Intravenous injection may be administered without further dilution
Dose adjustments are not required for patients with renal impairment; not recommended in end stage
renal disease patients undergoing dialysis
No dose adjustment based on age, or hepatic impairment
Product X is primarily eliminated by metabolism and by excretion in the urine.
None

PRODUCT X Profile
Clinical Studies

Product X was established as adjunctive therapy in partial-onset seizures with or without secondary
generalization in 3 fixed-dose, randomized, double-blind, placebo-controlled, 3 multicenter studies which
included over 1500 patients

Baseline
Demographics

Patients averaged 23 years since epilepsy diagnosis

One third of patients had tried 5 or more AEDs in his or her lifetime
Median baseline seizure frequency was 9 per month

Use of other AEDs

Most Common
Side Effects

Drug-drug
interactions
Pregnancy

Commonly used adjunctive AEDs

Carbamazepine (41%), lamotrigine (25%), valproate (21%), oxcarbazepine (16%), topiramate (14%),
phenytoin (10%) and levetiracetam (10%)
There was no observed benefit versus placebo when Product X was added to levetiracetam
In a pre-specified analysis of median percent reduction in partial onset seizure frequency by levetiracetam
status, Product X demonstrated efficacy over placebo in patients with prior exposure to levetiracetam
No additional safety or tolerability concerns were observed

Adverse Events
Most common are somnolence and dizziness
Adverse events reported were usually mild to moderate in intensity
Discontinuation Rates
The discontinuation rates due to adverse events were 6.0% to 7.4% in patients treated with Product X
The most common adverse event leading to discontinuation was dizziness
No food interaction
No evidence of any relevant drug-drug interactions with common AEDs or with oral contraceptives
containing ethinylestradiol and levonorgestrel
Product X is pregnancy category B3

PRODUCT X: Target Product ProfileEfficacy

P<.00001
P< 0.05

50mg/day

100mg/day

200mg/day

50mg/day

100mg/day

Clinical Studies

Product X was established as adjunctive therapy in partial-onset seizures with or

without secondary generalization in 3 fixed-dose, randomized, double-blind,
placebo-controlled, 3 multicenter studies which included over 1500 patients

Baseline
Demographics

Patients averaged 23 years since epilepsy diagnosis

One third of patients had tried 5 or more AEDs in his or her lifetime
Median baseline seizure frequency was 9 per month

200mg/day

PRODUCT X: Target Product ProfileSafety

TEAEs with incidence 5% patients in any treatment group

MedDRA
preferred term

Placebo

50mg/day

100mg/day

200mg/day

pooled

Somnolence

7%

11%

14%

17%

14%

Dizziness

6%

12%

9%

13%

11%

Headache

10%

15%

8%

17%

10%

3%

7%

8%

11%

8%

Drug-drug
interactions

Most Common
Side Effects

Fatigue

Adverse Events
Most common are somnolence and dizziness
Adverse events reported were usually mild to moderate in intensity
Discontinuation Rates
The discontinuation rates due to adverse events were 6.0% to 7.4% in
patients treated with Product X
The most common adverse event leading to discontinuation was dizziness

No food interaction
No evidence of any relevant drug-drug interactions with common AEDs or
with oral contraceptives containing ethinylestradiol and levonorgestrel

PRODUCT X: Additional Data Plate 1 Prior Levetiracetam (LEV) Use

1 Impact of PRIOR LEV use

Concomitant
treatment of
Product X and
Levetiracetam
Treatment with
Product X after
exposure to
Levetiracetam

Impact of CONCOMITTANT LEV use

In Studies 1 & 2, approximately 20% of the patients were on

concomitant levetiracetam.
Although the number of subjects is limited, there was no observed
benefit versus placebo when Product X was added to levetiracetam.
No additional safety or tolerability concerns were observed.

In Study 1, a pre-specified analysis of median percent reduction in partial

onset seizure frequency by levetiracetam status demonstrated efficacy
over placebo in patients with prior exposure to levetiracetam.

PRODUCT X: Additional Data Plate 2 Safety Profile

Incidence of non-psychotic behavioural TEAEs by pooled analysis

A third fewer patients on Product X

reported non-psychotic
behavioural TEAEs compared with
LEV
The placebo-adjusted incidence of
non-psychotic behavioural TEAEs
for Product X was approximately
50% lower than LEV

PRODUCT X: Additional Data Plate 3 - Response

Pre-Clinical Signal (Animal Models no human data available):
Penetration of blood-brain barrier
Estimated time of brain entry of product X, corrected half-times were 1-3 minutes

Physiochemical profile

Mechanism
of action

Dosing
Instructions

Product X is highly lipophilic

Initial dose of Product X is twice daily

No up-titration required, therapeutic dose achieved rapidly

Binding to synaptic vesicle proteins in the brain is considered to be the primary mechanism for
Product X anticonvulsant activity, however, the precise mechanism by which Product X exerts its
anticonvulsant activity has not been fully elucidated

PRODUCT X: Summary Positioning Plate

Based on what youve seen for Product X, how relevant are the below statements?
POS patients with unmet needs
Control over their seizures
30% refractory pat. live in
fear of the next seizure
High discontinuation rates
with existing options
Control over side effects
Tolerability issues often limit
optimal AED use
Patients highly dissatisfied
with available treatments

Control over regular routine

AED medication limits
patients in their daily live
Strong desire to lead a
normal life

Rank order of importance

What Product X can offer

POS
efficacy

Favorable
tolerability

Ease of use

Significant seizure reduction and responder rate in addon POS

High retention rate
Efficacy sustained independent of co-treatment with
enzyme inducers or inhibitors

Low AE incidence and placebo-like drop-out rates

Can be used combined with broad range of AEDs
No weight gain and no hematologic, hepatic and renal
lab abnormalities

No up-titration, can start at any effective dose

Can be taken with or without food
Potential for rapid brain uptake

Then rank sub-points in order of importance