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)
- - - - - -
- - - - - -
(c) p <0.01 compared to placebo
- - - - - -
- - - - - -
(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.
