Published: December 08, 2008
Multiple Vimpat(R) (lacosamide) Studies Presented at American Epilepsy Society Annual Meeting
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 inPhoenix 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:
-- Phase II SP 667 - 200, 400, 600 mg/day* Vimpat(R)
-- Phase III SP 754 - 400, 600 mg/day* Vimpat(R)
-- Phase III SP 755 - 200, 400 mg/day Vimpat(R)
* 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.
Poster Session 3, December 8, 2008, 8:00 - 9:00 am (Poster 3.256)
Michael Sperling, MD, David Rudd, PharmD, David Hebert, PhD, Pamela Doty,
PhD
Thomas Jefferson University, Philadelphia, PA; SCHWARZ BIOSCIENCES, Inc.,
(a member of the UCB Group), Research Triangle Park, NC, United States
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:
-- Carbamazepine (36.5 percent seizure frequency reduction with Vimpat(R)
400 mg/day vs. 21.7 percent with placebo)
-- Lamotrigine (33.3 percent vs. 18.3 percent)
-- Levetiracetam (37.6 percent vs. 17.6 percent)
-- Valproate (45.3 percent vs. 21.3 percent)
-- Topiramate (41.4 percent vs. 28.5 percent)
-- Oxcarbazepine (27.2 percent vs. 12.5 percent)
Similar results were seen for responder rates (patients with 50 percent or
greater reduction in seizure frequency):
-- Carbamazepine (37.4 percent responder rate with Vimpat(R) 400 mg/day
vs. 26.4 percent placebo)
-- Lamotrigine (34.2 percent vs. 19.0 percent)
-- Levetiracetam (43.4 percent vs. 19.4 percent)
-- Valproate (47.5 percent vs. 26.9 percent)
-- Topiramate (41.9 percent vs. 25.6 percent)
-- Oxcarbazepine (29.7 percent vs. 17.6 percent)
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).
-- TEAEs were mild to moderate and appeared to be dose-related.
-- The incidence of weight gain and other troublesome TEAEs such as
somnolence and cognitive and psychiatric AEs appeared low:
-- The incidence of somnolence was 7 percent for the Vimpat(R)-treated
group vs. 5 percent for placebo
-- The incidence of memory impairment was 2 percent for both Vimpat(R)
and placebo groups
-- The incidence of depression was 2 percent for the Vimpat(R)-treated
group and 1 percent for placebo
-- The incidence of weight gain was 1 percent for both Vimpat(R) and
placebo groups
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.
Further information
Andrea Levin
Public Relations Manager
T 770.970.8352
M 404.483.7329
Andrea.levin@ucb-group.com
Eimear O'Brien,
Global CNS Communications Manager, UCB Group
T +32.2.559.9271
Eimear.OBrien@ucb-group.com
About UCB
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 (symbol:
UCB). Worldwide headquarters is located inBrussels, Belgium; U.S.
headquarters is located inAtlanta, Georgia. For more information about UCB,
visit www.ucb-group.com.
Forward looking statement
This press release contains forward-looking statements based on current
plans, estimates and beliefs of management. Such statements are subject to
risks and uncertainties that may cause actual results to be materially
different from those that may be implied by such forward-looking statements
contained in this press release. Important factors that could result in such
differences include: changes in general economic, business and competitive
conditions, effects of future judicial decisions, changes in regulation,
exchange rate fluctuations and hiring and retention of its employees.
SOURCE UCB
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