Valeant Pharmaceuticals International (NYSE:VRX) today reported
positive results for retigabine in RESTORE 1, the first 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 1 evaluated the 1200 mg daily dose of retigabine (the highest
dose in the RESTORE program) versus placebo in patients taking stable
doses of 1 - 3 additional anti-epileptic drugs (AEDs). Retigabine
demonstrated statistically significant results on the primary efficacy
endpoints important for regulatory review by both the US Food and Drug
Administration (FDA) and the European Medicines Evaluation Agency
(EMEA). These results build upon the positive findings observed in
Study 205 which was published in the journal Neurology in April 2007.
"We are very pleased with the results of this important Phase III
clinical trial," said J. Michael Pearson, Valeant´s chairman and chief
executive officer. "These data confirm the efficacy seen with
retigabine in earlier clinical trials and put Valeant at the forefront
of development of neuronal potassium channel openers for the treatment
of epilepsy and other central nervous system diseases. Results from
RESTORE 2, our second pivotal Phase III clinical trial studying lower
doses of retigabine, are expected during the second quarter. We
anticipate filing a New Drug Application (NDA) for retigabine with the
FDA and a Marketing Authorization Application (MAA) to the EMEA before
the end of this year."
"These results are very encouraging and support the growing body
of evidence to suggest that retigabine may be an effective adjunctive
therapy for partial onset seizures," said Jacqueline A French, M.D.,
Professor of Neurology, New York University Medical Center. "There is
a significant need for novel anti-epileptic drugs because
approximately one-third of patients with epilepsy continue to
experience seizures despite treatment with currently available
medications. Retigabine works by a unique mechanism of action and it
could potentially play a significant role in the management of
epilepsy."
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SUMMARY EFFICACY DATA
RTG 1200 mg Placebo
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Median reduction in 28-day total 44.3%(c) 17.5%
partial seizure frequency(a) (ITT) n=151 n=150
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Median reduction in 28-day total 54.5%(c) 18.9%
partial seizure frequency during n=119 n=137
Maintenance Phase
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Responder Rate(d) (ITT) 45.0%(c) 18.0%
n=151 n=150
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Responder Rate during Maintenance 55.5%(c) 22.6%
Phase(b) n=119 n=137
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ITT population defined as all subjects taking at least 1 dose of study
medication and having at least 1 efficacy assessment
(a) FDA endpoint
(b) Endpoint per EU Committee for Human Medicinal Products (CHMP)
(c) p less than 0.0001 compared to placebo
(d) Responder Rate defined as greater than or equal to 50% reduction
in 28-day total partial seizure frequency
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During RESTORE 1, 26.8 percent of patients in the retigabine arm
and 8.6 percent of patients in the placebo arm withdrew due to adverse
events. The most common side effects associated with retigabine in
RESTORE 1 included dizziness, somnolence, fatigue, confusion,
dysarthria, ataxia, blurred vision, tremor, and nausea. Comprehensive
efficacy and safety results from RESTORE 1 are planned to be presented
at upcoming scientific meetings in the United States and the European
Union.
RESTORE 1 Trial Design
The RESTORE 1 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 a fixed dose of 1200 mg/day of retigabine,
administered in three divided doses, compared to placebo. The study
enrolled 306 patients, ranging in age from 18 to 71 years old, and was
conducted at 49 sites across the United States, Argentina, Mexico,
Brazil and Canada. Study duration was 32 weeks including 8 weeks
baseline phase, 6 weeks titration phase, 12 weeks maintenance phase
and 6 weeks transition phase. Following completion of RESTORE 1
patients were offered the opportunity to continue treatment with
retigabine in an open-label extension study.
RESTORE 1 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.
At the completion of the RESTORE trials, retigabine will have been
studied in more than 1,750 subjects, including more than 1,350
patients with epilepsy. More than 350 of these patients will have
taken retigabine for twelve or more months, including a few who have
taken retigabine for six or more years.
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.
Conference Call and Webcast Information:
Valeant will host a conference call and webcast on Thursday,
February 14, 2008 at 12:00 p.m. EST (9:00 a.m. PST) 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 34933527. International callers should dial (706)
679-0845, confirmation code 34933527. 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 34933527.
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 an 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 Valeant
Valeant Pharmaceuticals International (NYSE:VRX) is a global
specialty pharmaceutical company that develops, manufactures and
markets a broad range of pharmaceutical products primarily in the
areas of neurology, infectious disease and dermatology. More
information about Valeant can be found at www.valeant.com.
FORWARD-LOOKING STATEMENTS
This press release contains forward-looking statements, including,
but not limited to, statements regarding expectations or plans of the
company´s Phase III program for retigabine and the potential role
retigabine could play in managing epilepsy. 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, including that RESTORE 1 results are not
necessarily predictive of RESTORE 2 results, and that adverse events
are not always immediately apparent even in well designed clinical
trials, regulatory approval processes, 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.
