ATLANTA, Dec. 8 /PRNewswire/ -- UCB today announced new findings from analyses of pooled Vimpat(R) (lacosamide) clinical trial data, demonstrating that the new antiepileptic drug (AED) starts working during the first week of treatment and across doses in a challenging patient population, when administered as adjunctive therapy. The analyses also showed that Vimpat(R) provides consistent seizure reduction versus placebo, when added to concomitant AEDs, and that it is generally well-tolerated. These data were presented at the 62nd annual meeting of the American Epilepsy Society in Seattle.
"These data show that Vimpat(R) may help fill a considerable treatment gap as an add-on therapy for people living with epilepsy whose partial onset seizures are not controlled," said Steve Chung, director of clinical epilepsy research at Barrow Neurological Institute in Phoenix and a lead investigator for the Vimpat(R) clinical trial program. "In general, patients who participated in these trials had lived with epilepsy for an average of over 20 years and had not found seizure control despite trying multiple AEDs. Yet, Vimpat(R) provided significant seizure reduction, compared to placebo, when added to their existing treatment regimen."
The U.S. Food and Drug Administration (FDA) approved Vimpat(R) in October 2008 for use as an add-on therapy for the treatment of partial-onset seizures in people with epilepsy who are 17 years and older. Vimpat(R) has a novel mechanism of action that is different from all currently available AEDs. The drug will be available in U.S. pharmacies in the first quarter of 2009.
Trials Conducted in Challenging Patient Population
All four analyses evaluated pooled data from one phase II and two phase III multi-center, fixed dose, randomized, double-blind, placebo-controlled clinical trials, evaluating Vimpat(R) as adjunctive therapy. The studies and treatment arms included:
* The 600 mg/day dose of Vimpat(R) is not approved by the FDA. In clinical trials, the 600 mg daily dose was not more effective than the 400 mg daily dose, and was associated with a substantially higher rate of adverse reactions. Vimpat(R) dosing should start at 50 mg twice daily and maybe increased to a daily dose of 200 to 400 mg per day (recommended therapeutic dosing) administered in two divided doses.
The primary endpoints of the studies were the median percent reduction in seizure frequency per 28 days from the baseline to the maintenance period and the 50 percent responder rate, defined as the proportion of patients experiencing a 50 percent or greater reduction in partial seizure frequency per 28 days from the baseline to the maintenance period.
The studies involved a total of more than 1,300 patients, with 944 randomized to receive Vimpat(R) at one of the three doses (200 mg/day, n=270; 400 mg/day, n=471; 600 mg/day, n=203) and 364 randomized to the placebo group. Patients in the treatment groups received Vimpat(R) at 100 mg/day (50 mg twice daily) during the initial week of treatment, followed by weekly titration in 100 mg/day increments to the assigned targeted dose.
This patient group had been living with epilepsy for an average of almost 24 years. Overall, 77.4 percent of patients had tried four or more AEDs in their lifetime and 45.2 percent had tried seven or more. Most patients (84.4 percent) were taking two or three concomitant AEDs at the time of study entry, mainly carbamazepine (35.2 percent), lamotrigine (31.2 percent), levetiracetam (29.0 percent), valproate (23.6 percent), and topiramate (22.3 percent). At baseline, patients reported more than two to three times the number of seizures per 28 days required by the inclusion criteria.
A total of 87 percent of patients in the placebo group completed treatment, as did 82 percent, 77 percent, and 62 percent in the 200, 400, and 600 mg/day Vimpat(R) groups.
Summary of Vimpat(R) Data Presented at 2008 AES Annual Meeting
Early Onset of Efficacy in the Initial Weeks of Treatment with Lacosamide: A Pooled Analysis of Three Phase II/III Trials
This analysis found that Vimpat(R) demonstrated statistically significant efficacy as early as the first week of treatment, with consistently significant results for both primary endpoints starting at doses of 100 mg/day.
-- At the end of the first week of treatment in this study, when all participants in the active treatment groups were receiving 100 mg/day of Vimpat(R), a significant reduction in seizure frequency was observed versus placebo (33.0 percent Vimpat(R) group vs. 19.4 percent placebo; p<.01). Also during the first week, 39.1 percent of patients treated with Vimpat(R) experienced a 50 percent or greater reduction in seizures, compared with 31.3 percent in the placebo group (p<.01).
-- By the end of the second week of treatment, when all participants in the treatment groups were receiving 200 mg/day of Vimpat(R), a significant reduction in seizure frequency was observed versus placebo (34.0 percent Vimpat(R) group vs. 20.0 percent placebo; p<.01). The percentage of patients with a 50 percent or greater reduction in seizure frequency was 40.2% for patients receiving Vimpat(R) and 32.2 percent for placebo (p<.01 vs. placebo).
-- These significant seizure reductions appeared to be maintained over subsequent weeks of Vimpat(R) treatment.
Evaluation of Lacosamide Efficacy in Subjects with Partial-Onset Seizures Across the Dose Range Used in Phase II/III Clinical Trials
In the individual trials and pooled analysis in this evaluation, Vimpat(R) significantly reduced seizures at all doses studied (200, 400, and 600 mg/day). The individual trials demonstrated that:
-- The 400 and 600 mg/day Vimpat(R) dose groups were significantly different from placebo for both primary efficacy endpoints in all trials using these doses.
-- The 200 mg/day Vimpat(R) dose group demonstrated significant seizure reduction versus placebo in the phase III trial (SP 755), but not in the phase II trial (SP667). To further evaluate the effectiveness of the 200 mg/day dose, a meta-analysis was conducted; results showed a significant difference compared to placebo for both primary endpoints.
The pooled results among patients entering the maintenance period demonstrated statistically significant reductions in seizure frequency at all doses studied compared to placebo:
-- Seizure frequency was significantly reduced by 33.5 percent for the 200 mg/day group (p <.05 ) and by more than 40 percent for the 400 and 600 mg/day groups (41.4 percent and 48.8 percent, respectively), compared with 19.2 percent for placebo (p<.0001).
-- Responder rates (patients with 50 percent or greater reduction in seizure frequency) were 34.8 percent for 200 mg/day (p <.05), 44.3 percent for 400 mg/day, and 48.6 percent for 600 mg/day, and 23.1 percent for placebo (p<.0001).
-- Additionally, there was a dose-responsive trend for improved seizure freedom rates among subjects who completed the maintenance period (2.7 percent, 3.3 percent, and 4.8 percent with increasing Vimpat(R) doses vs. 0.9 percent for placebo) and also for median increase in percentage of seizure-free days (7.4 percent, 9.3 percent, and 12.1 percent vs. 5.4 percent for placebo) for those entering the maintenance period.
The pooled results among all patients in the intent-to-treat analysis, including those who dropped out during the titration period, also demonstrated statistically significant reductions in seizure frequency at all doses studied compared to placebo:
-- Seizure frequency was reduced by 33.3 percent for the 200 mg/day group, 36.8 percent for the 400 mg/day group, and by 39.4 percent for the 600 mg/day group, compared with 18.4 percent for placebo (p<.05 for the 200 mg/day group and p<.0001 for the 400 and 600 mg/day groups vs. placebo).
-- Responder rates were 34.1 percent for 200 mg/day, 39.7 percent for 400 mg/day, and 39.6 percent for 600 mg/day, compared with 22.6 percent for placebo (p<.05 for the 200 mg/day group and p<.0001 for the 400 and 600 mg/day groups vs. placebo).
Poster Session 3, December 8, 2008, 8:00 - 9:00 am (Poster 3.196)
Steve Chung, MD, David Rudd, David Hebert, PhD, Pamela Doty
Barrow Neurological Institute, Phoenix, AZ; SCHWARZ BIOSCIENCES (a member of the UCB Group), Research Triangle Park, Raleigh, North Carolina
Lacosamide Efficacy is Independent of Concomitant AED(s) Treatment
This analysis evaluated pooled data from the placebo and 400 mg/day Vimpat(R) treatment groups of each trial by the most frequently used concomitant AEDs. The most commonly used concomitant AEDs for this patient population were carbamazepine, lamotrigine, levetiracetam, valproate, and oxcarbazepine.
Overall, reduction in seizure frequency was 36.8 percent for adjunctive treatment with Vimpat(R) 400 mg/day versus 18.4 percent for adjunctive treatment with placebo. When analyzed by individual concomitant AED use, Vimpat(R) appeared to provide a similar magnitude of seizure reduction versus placebo regardless of which AED was included as part of the patients' baseline treatment regimen, which included one to three concomitant AEDs:
Similar results were seen for responder rates (patients with 50 percent or greater reduction in seizure frequency):
Poster Session 3, December 8, 2008, 8:00 - 9:00 am (Poster 3.246)
William Rosenfeld, MD, David Rudd, PharmD, David Hebert, PhD, Pamela Doty, PhD
The Comprehensive Epilepsy Care Center for Children and Adults, St. Louis, Missouri
Schwarz Biosciences Inc. (a member of the UCB Group), Raleigh, NC, USA
Safety and Tolerability of Lacosamide: A Summary of Adverse Events in Epilepsy Clinical Trials
This pooled analysis clinical trial safety data showed Vimpat(R) to be generally well-tolerated, although 85 percent of trial participants were already taking two to three concomitant AEDs upon trial entry:
-- The most frequently reported individual treatment emergent adverse events (TEAE) occurring in greater than or equal to 10 percent of the Vimpat(R) group and greater than placebo were dizziness (31 percent vs. 8 percent), headache (13 percent vs. 9 percent), nausea (11 percent vs. 4 percent), and diplopia (11 percent vs. 2 percent).
Poster Session 3, December 8, 2008, 11:30 am - 12:30 pm (Poster 3.245)
V. Biton, N. Fountain, F. Rosenow, A. Gil-Nagel, T. Sullivan, D. Hebert, P. Doty
Clinical Trials, Inc., Little Rock, Arkansas; University of Virginia, Charlottesville, Virginia; Philipps-University, Department of Neurology, Marburg, Germany; Hospital Ruber Internacional, Madrid, Spain; SCHWARZ BIOSCIENCES (a member of the UCB Group), Raleigh, North Carolina
Important safety information about Vimpat(R) in the U.S.
Vimpat(R) tablets are indicated as adjunctive therapy in the treatment of partial-onset seizures in patients with epilepsy who are 17 years and older. Vimpat(R) injection is indicated as short-term replacement when oral administration is not feasible in these patients. Patients should be advised that Vimpat(R) may cause dizziness, ataxia, and syncope. Caution is advised for patients with known cardiac conduction problems, who are taking drugs known to induce PR interval prolongation, or with severe cardiac disease. In patients with seizure disorders, Vimpat(R) should be gradually withdrawn to minimize the potential of increased seizure frequency. Multiorgan hypersensitivity reactions have been reported with antiepileptic drugs. If this reaction is suspected, treatment with Vimpat(R) should be discontinued.
AEDs increase the risk of suicidal behavior and ideation. Patients taking Vimpat(R) should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.
The most common adverse reactions occurring in >10 percent of Vimpat(R)-treated patients, and greater than placebo, were diplopia, headache, dizziness, and nausea.
The FDA has recommended Vimpat(R) as a schedule C-V controlled substance. Scheduling is expected to be finalized in the first quarter of 2009.
Please go to http://www.fda.gov/cder/foi/label/2008/022253lbl.pdf for approved prescribing information.
UCB is a global leader in the biopharmaceutical industry dedicated to the research, development and commercialization of innovative medicines with a focus on the fields of central nervous system and immunology disorders. Employing approximately 12,000 people in more than 40 countries, UCB achieved revenue of 3.6 billion euro in 2007. UCB is listed on NYSE Euronext . Worldwide headquarters is located in Brussels, Belgium; U.S. headquarters is located in Atlanta, Georgia. For more information about UCB, visit www.ucb-group.com.
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