Valeant Announces Successful Completion of Retigabine Phase III Epilepsy Program Validating Novel Mechanism of Action

13/05/2008 - 16:00

Valeant Pharmaceuticals International (NYSE:VRX) today reported positive

results for retigabine in RESTORE 2, the second of two Phase III pivotal

trials, for this first-in-class neuronal potassium channel opener.

Retigabine is being developed as an adjunctive treatment for adult

epilepsy patients with refractory partial onset seizures. RESTORE 2

evaluated the 600 and 900 mg daily doses of retigabine versus placebo in

patients taking stable doses of one to three additional anti-epileptic

drugs (AEDs). Retigabine at both the 600 mg and 900 mg doses

demonstrated highly statistically significant results on the primary

efficacy endpoints important for regulatory review by both the U.S. Food

and Drug Administration (FDA) and the European Medicines Evaluation

Agency (EMEA).
These results build upon the positive data at the 1200 mg dose in the

RESTORE 1 study reported earlier this year. With the completion of the

phase III program, retigabine has now been studied in more than 1,750

subjects, including more than 1,350 patients with epilepsy. More than

350 of these patients have taken retigabine for twelve or more months

including a few who have taken retigabine for six or more years. Valeant

plans to submit a New Drug Application (NDA) with the FDA and a

Marketing Authorization Application (MAA) with the EMEA before the end

of this year.
"We are extremely pleased with the efficacy

and tolerability profile of retigabine as demonstrated in the RESTORE 2

study," said J. Michael Pearson, Valeant´s

chairman and chief executive officer. "These

positive results further confirm the utility of selective potassium

channel openers in refractory partial onset epilepsy. With our Phase III

program now complete, we are excited both about the important medical

advance retigabine represents in treating epilepsy patients, and the

significant commercial opportunity this represents for Valeant."
"There is increasing evidence that medications

with novel mechanisms of action improve outcomes in patients with

refractory epilepsy," said RESTORE 2 principal

investigator Martin Brodie, M.D., Clinical and Research Director

Epilepsy Unit, University of Glasgow, Scotland. "This

has been clearly demonstrated in the retigabine program, which has shown

clinically meaningful results across a range of doses, providing greater

flexibility to physicians in their efforts to treat the many patients

with this potentially serious neurological disease."

= = = = = = = = = = =

SUMMARY EFFICACY DATA

- - - - - -

Placebo

RTG 600 mg

RTG 900 mg
- - - - - -

Median reduction in 28-day total partial seizure frequency(a) (ITT)

15.9%
n=179

27.9%(c)
n=181

39.9%(c)
n=178

- - - - - -

Median reduction in 28-day total partial seizure frequency during

Maintenance Phase

17.4%
n=164

35.3%(c)
n=158

44.3%(c)
n=149

- - - - - -

Responder Rate(d) (ITT)

17.3%
n=179

31.5%(c)
n=181

39.3%(c)
n=178

- - - - - -

Responder Rate during Maintenance Phase(b)

18.9%
n=164

38.6%(c)
n=158

47.0%(c)
n=149

- - - - - -

ITT population defined as all subjects taking at least 1 dose of

study medication
- - - - - -

- - - - - -

(a) FDA endpoint
- - - - - -

- - - - - -

(b) Endpoint per EU Committee for Human Medicinal Products (CHMP)
- - - - - -

- - - - - -

(d) Responder Rate defined as ? 50%

reduction in 28-day total partial seizure frequency

- - - - - -

During RESTORE 2, 14.4 and 25.8 percent of patients in the retigabine

600 mg and 900 mg arms respectively and 7.8 percent of patients in the

placebo arm withdrew due to adverse events. As expected, the most common

side effects associated with retigabine in RESTORE 2 included dizziness

somnolence, and fatigue and were generally seen at much lower rates than

at a 1200 mg dose in the RESTORE 1 trial. Comprehensive efficacy and

safety results from RESTORE 2 are planned to be presented at upcoming

scientific meetings in the United States and the European Union.
RESTORE 2 Trial Design
The RESTORE 2 trial (RESTORE stands for Retigabine

Efficacy and Safety

Trials for Partial Onset

Epilepsy) consisted of

randomized, double-blinded, placebo-controlled, multi-center, parallel

groups and assessed the efficacy and safety of retigabine compared to

placebo in adult patients with epilepsy who were experiencing refractory

partial-onset seizures despite receiving one, two or three AEDs. The

study evaluated fixed doses of 600 and 900 mg/day of retigabine

administered in three divided doses, compared to placebo. The study

enrolled 539 patients, ranging in age from 18-75 years old, and was

conducted at 69 sites across Europe, Israel, Australia, South Africa and

the United States. Study duration was 30 weeks including 8 weeks

baseline phase, 4 weeks forced titration phase, 12 weeks maintenance

phase and 6 weeks transition phase. Following completion of RESTORE 2

patients were offered the opportunity to continue treatment with

retigabine in an open-label extension study and 92% percent of eligible

patients chose to rollover into the extension study.
RESTORE 2 was designed to meet regulatory guidance from both the FDA and

the CHMP. The trial was conducted under a Special Protocol Assessment by

the FDA.
Retigabine has not been found by the FDA or any other regulatory agency

to be safe or effective in the diagnosis, mitigation, treatment or cure

of any disease or illness. It may not be sold or promoted in the United

States unless and until the FDA has approved an NDA. Similar

restrictions apply in other countries.
About Epilepsy
Epilepsy is one of the most common neurological diseases, affecting

approximately 50 million people worldwide. It is a brain disorder in

which clusters of nerve cells, or neurons, in the brain sometimes signal

abnormally. In epilepsy, the normal pattern of neuronal activity becomes

disturbed, causing a seizure. Seizures can cause changes in behavior and

emotions, strange sensations and sometimes convulsions, muscle spasms

and loss of consciousness.
Approximately 30 percent of people with epilepsy experience seizures

that are not adequately controlled with currently prescribed AEDs.

Individuals with epilepsy who do not achieve remission with AEDs are

often severely disabled by their condition, have an unsatisfactory

quality of life and are at increased risk of sudden unexpected death.

Refractory epilepsy is associated with memory loss, lower levels of

school performance, depression and impaired psychosocial skills.
About Potassium Channel Openers
Potassium channels are one of the voltage-gated ion channels found in

neuronal cells and are important determinants of neuronal activity.

Numerous ion-channel mutations have been linked to epilepsy, and many

antiepileptic medications modulate sodium or calcium channels. Potassium

channels have been demonstrated in animal models to be critical in

regulating membrane potential. Retigabine is the first potassium channel

opener to reach late stage clinical development. It is believed that by

facilitating the opening of specific neuronal potassium channels

retigabine causes a hyperpolarizing shift in the potassium current and

thereby reduces the excitability of neuronal cells. Dampening of

neuronal excitability is an important mechanism for reducing the

potential for seizures.
About Retigabine Program
Retigabine was investigated in the Retigabine Efficacy and Safety Trials

for partial Onset Epilepsy (RESTORE) trials, two large Phase III trials

that evaluated the safety and efficacy of retigabine in refractory

epilepsy patients who are receiving one, two, or three antiepileptic

drugs (AEDs). In November 2007, Valeant initiated a Phase II clinical

trial of retigabine for the treatment of pain associated with

postherpetic neuralgia (PHN), a painful and common complication of

shingles. Valeant expects to have data available from this study in

2009. Valeant is currently developing a modified release formulation in

order to provide a more convenient dosing schedule. In addition, Valeant

is also evaluating the potential use of retigabine in treating other

indications.
About Valeant
Valeant Pharmaceuticals International (NYSE:VRX) is a multinational

specialty pharmaceutical company that develops and markets a broad range

of pharmaceutical products primarily in the areas of neurology and

dermatology. More information about Valeant can be found at www.valeant.com.
Conference Call and Webcast Information:
Valeant will host a conference call and webcast on Tuesday, May 13, 2008

at 1:00 p.m. EDT (10:00 a.m. PDT) to discuss the results from its Phase

III clinical trial. A webcast of this event will be available live over

the Internet along with a slide presentation. The webcast may be

accessed through the investor relations section of Valeant´s

corporate Web site at www.valeant.com.

The dial-in number to participate on this call is (877) 295-5743

confirmation code 47295455. International callers should dial (706)

679-0845, confirmation code 47295455. Interested parties will have

access via the Internet and on the conference call to ask questions

following the presentation. A replay will be available approximately two

hours following the conclusion of the conference call and can be

accessed by dialing (800) 642-1687, or (706) 645-9291, confirmation code

47295455.
FORWARD-LOOKING STATEMENTS
This press release contains forward-looking statements, including, but

not limited to, statements regarding expectations or plans of the company´s

development program for retigabine and the potential role retigabine

could play in managing epilepsy and in treating other indications, and

the commercial opportunity retigabine may present for Valeant. These

statements are based upon the current expectations and beliefs of

management and are subject to certain risks and uncertainties that could

cause actual results to differ materially from those described in the

forward-looking statements. These risks and uncertainties include, but

are not limited to, risks and uncertainties related to the clinical

development of retigabine, the fact that adverse events are not always

immediately apparent even in well designed clinical trials, regulatory

approval processes, the potential that competitors may bring to market

drugs or treatments that are more effective or more commercially

attractive than retigabine, and other risks and uncertainties discussed

in the company´s filings with the SEC.

Valeant wishes to caution the reader that these factors are among the

factors that could cause actual results to differ materially from the

expectations described in the forward-looking statements. Valeant also

cautions the reader that undue reliance should not be placed on any of

the forward-looking statements, which speak only as of the date of this

release. The company undertakes no obligation to update any of these

forward-looking statements to reflect events or circumstances after the

date of this release or to reflect actual outcomes.