Long-term Use of Antiepileptic Drug Vimpat (Lacosamide) C-V Reduced Seizure Frequency and Severity and Improved Health-related Quality of Life Measures
Data presented at the 65th Annual Meeting of the American
Epilepsy Society
-- First presentation of pooled Vimpat® data showed a decrease
in partial-onset seizure frequency and consistent efficacy in
patients undergoing open-label treatment for up to eight
years.
-- Long-term treatment with Vimpat® was associated with
statistically significant improvements in health-related quality of
life standards, including seizure worry, social functioning, and
overall health state.
ATLANTA, Dec. 5, 2011 /PRNewswire/ -- UCB today announced new
findings for Vimpat® (lacosamide) C-V that offer additional
support regarding the long-term effects of the antiepileptic drug
(AED) as an adjunctive therapy for adults with uncontrolled
partial-onset seizures. The data demonstrate reduced seizure
severity and improvements in measures of health-related quality of
life (HRQoL). These and other Vimpat® data were presented
at the 65th Annual Meeting of the American Epilepsy Society (AES)
in Baltimore, Md.
Analyses of pooled data from open-label extensions of several Phase II/III trials showed that treatment with lacosamide was generally well-tolerated and associated with decreased partial-onset seizures for up to eight years.
"Collectively, this body of evidence showed that lacosamide reduced seizure frequency and improved health-related quality of life, as reported by patients. And these effects were maintained over a long-term basis," said Dr. William Rosenfeld, M.D., Director, The Comprehensive Epilepsy Care Center for Children and Adults, St. Louis, Mo.
Additional analyses of pooled data from open-label extensions of several Phase II/III trials highlighted patients' self-reported improvements in HRQoL during long-term treatment with lacosamide. Specific areas of improvements reported by patients were seizure worry and social functioning. Patients also consistently reported feelings of improvements in their overall health state.
Vimpat® is indicated as adjunctive therapy for the treatment of partial-onset seizures in adults with epilepsy. The most common adverse reactions reported in pivotal trials and occurring in 10 percent or more of Vimpat®-treated patients, and greater than placebo, were dizziness, headache, nausea, and diplopia. Additional important safety information for Vimpat® is available at the end of the press release.
Data presented at AES used the following measurement scales:
Quality of Life in Epilepsy scale (QOLIE-31) is an
epilepsy-specific assessment with 31 questions that ask patients
about their health-related quality of life. Responses to the
questions are ranked on a scale of 0 (worst possible quality of
life) to 10 (best possible quality of life).
Seizure Severity Questionnaire (SSQ) allows patients to review
various aspects of their seizures, such as altered consciousness
and cognitive, emotional, and physical effects.
Patient Global Impression of Change (PGIC) is a scale that allows
patients to rank how much they think their condition has changed
during the treatment period of the trial. The scale ranges
from 0 (much better) to 10 (much worse).
Summary of Vimpat ® Data:
Abstract 2.233 : Evaluation of Long-Term Treatment with Lacosamide
for Partial-Onset Seizures: A Pooled Analysis of Open-Label
Extension Trials
This analysis of pooled data from three open-label extension trials
examined the effects of open-label treatment with lacosamide
exposure up to 8 years in patients with partial-onset
seizures. A total of 1,054 patients initiated open-label
lacosamide treatment, representing 2,997.8 patient-years
exposure. Results showed that treatment with lacosamide up to
eight years was generally well tolerated and associated with a
reduction in seizure frequency and maintenance of efficacy over
time. Additionally, no new safety concerns were identified
related to long-term treatment with lacosamide.
The median modal dose of lacosamide (i.e., the dose that patients used most often during the trial) was 400mg/day for a minimum treatment duration of three days up to a maximum duration of 2,913 days (~8 years). The median maximum daily dose was 500 mg/day. However, the maximum FDA-approved dose for Vimpat® is 400 mg/day.
Abstract 2.244: Effect of Long-Term Lacosamide on Patient-Reported
Health-Related Quality of Life and Seizure Severity by Seizure
Subtype
This analysis of pooled data from open-label extensions of three Phase II/III trials demonstrated that long-term lacosamide therapy was associated with improvements in HRQoL and substantial reductions in seizure severity among adults with complex partial seizures (CPS) and secondary generalized partial seizures (SGPS) who responded to treatment. Improvements in HRQoL and reduction in seizure severity were greater in patients who achieved a 50 percent reduction in seizure frequency compared to individuals who did not respond to treatment.
For QOLIE-31:
At Week 48, CPS responders (n=362) reported improvements in all
QOLIE-31 scores with clinically meaningful improvements
specifically in seizure worry (+10.81) and social functioning
(+4.03). CPS non-responders (n=267) had substantially smaller
improvement in seizure worry and social functioning, and worsening
in all other scores.
At Week 48, SGPS responders (n=183) showed clinically meaningful
improvements in seizure worry (+13.34), overall quality of life
(+6.75), social functioning (+7.26), and total score (+5.36).
SGPS non-responders (n=99) had meaningful improvement in social
functioning (+4.25), but smaller improvements or worsening in all
other scores.
For SSQ:
CPS responders (n=244) reported substantially improved severity
scores of up to -1.16 on the overall score, with non-responders
(n=196) reporting smaller changes of up to -0.54.
SGPS responders (n=132) reported improvements of up to -1.24 for
overall score, with non-responders (n=75) reporting smaller changes
of up to -0.63.
Abstract 2.246: Lacosamide Added to Concomitant AEDs Grouped by
Mechanism of Action – Impact on Patient-Reported
Health-Related Quality of Life in Pooled Phase II/III Trials
This post-hoc analysis of pooled data from open-label extensions of three Phase II/III trials found that the impact of treatment with lacosamide on HRQoL was dependent on the dose and sodium channel properties of the concomitant AED regimen. However, adding lacosamide up to 400 mg/day for patients taking any combination of AEDs led to generally stable HRQoL.
Abstract 2.245: Improved Seizure Severity, Health-Related Quality
of Life and Health Status Reported by Patients During Long-Term
Treatment with Lacosamide: Analysis of Pooled Open-Label Data
This analysis of pooled data from open-label extensions of three
Phase III trials demonstrated that after one year of lacosamide
treatment, patients reported significant improvements in seizure
severity and HRQoL, including seizure worry, social functioning,
and overall health state.
For QOLIE-31:
On average, patients reported improvements on all QOLIE-31
subscales with the exception of medication effects.
Significant improvements were found for seizure worry (+7.36),
social functioning (+2.84), and total score (+1.66).
At Week 48, at least one-third of patients showed clinically
meaningful improvement on all QOLIE-31 subscales, specifically
seizure worry (47.7 percent) and social functioning (47.7
percent).
For SSQ:
At Week 48, patients reported a significant mean improvement on all
SSQ subscales, including cognitive, emotional, and physical effects
during and after seizures.
For PGIC:
A majority of patients (67.7 percent) reported improvement in their
overall health state, with nearly half (46.9 percent) placed in the
"very much" or "much improved" categories.
About Epilepsy
Epilepsy is a chronic neurological disorder affecting approximately
50 million people worldwide and three million people in the
U.S. Anyone can develop epilepsy; it occurs across all ages,
races and genders. Uncontrolled seizures and medication side
effects pose challenges to independent living, learning and
employment, so the goal of epilepsy treatment is seizure freedom
with minimal side effects. In the U.S., more than one million
patients continue to have seizures despite initial therapy, and
more than 800,000 continue to have seizures despite treatment with
two or more therapies. (1),(2)
About Vimpat ®
Vimpat® tablets and injection were launched in the US in May
2009 as an add-on therapy for the treatment of partial-onset
seizures in people with epilepsy who are aged 17 years and
older. Vimpat® injection is a short-term replacement when
oral administration is not feasible in these patients.
Vimpat® oral solution was launched in June 2010. The
availability of the oral tablets, oral solution, and intravenous
(IV) injection allows for consistent treatment in a hospital
setting. The most common adverse reactions occurring in
greater than or equal to 10 percent of Vimpat®-treated
patients, and greater than placebo, were dizziness, headache,
nausea, and diplopia. Additional important safety information
for Vimpat® is available at the end of the press release.
In the European Union, Vimpat® (film-coated tablets and solution for infusion) is approved as adjunctive therapy for the treatment of partial-onset seizures with or without secondary generalization in patients with epilepsy aged 16 years and older. Vimpat® solution for infusion may be used when oral administration is temporarily not feasible.
The maximum approved daily dose for Vimpat® in the European Union and the U.S. is 400 mg/day.
Important safety information about Vimpat ® in the U.S.
Warnings and Precautions
AEDs increase the risk of suicidal behavior and ideation. Patients
taking Vimpat® should be monitored for the emergence or
worsening of depression, suicidal thoughts or behavior, and/or any
unusual changes in mood or behavior.
Patients should be advised that Vimpat® 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® 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® should be discontinued.
Vimpat® oral solution contains aspartame, a source of phenylalanine. A 200 mg dose of Vimpat® oral solution (equivalent to 20 mL) contains 0.32 mg of phenylalanine.
Common Adverse Reactions
The most common adverse reactions occurring in greater than or
equal to 10 percent of Vimpat®-treated patients, and greater
than placebo, were dizziness, headache, nausea, and diplopia.
Dosage adjustments are recommended for patients with mild or
moderate hepatic impairment or severe renal impairment. The
use of Vimpat® in patients with severe hepatic impairment is
not recommended.
For full prescribing information on Vimpat®, visit http://www.vimpat.com/prescribing-information.aspx (Accessed 18 October, 2011).
For more information on Vimpat®, visit www.Vimpat.com or contact UCB at (800) 477-7877.
Vimpat® (C-V) is a Schedule V controlled substance.
Vimpat® is a registered trademark used under license from Harris FRC Corporation.
Important safety information about Vimpat ® in the EU and
EEA
Vimpat® is indicated as adjunctive therapy in the treatment of
partial-onset seizures with or without secondary generalization in
patients with epilepsy aged 16 years and older. Lacosamide solution
for infusion is an alternative for patients when oral
administration is temporarily not feasible. Contraindications:
Hypersensitivity to the active substance or any of the excipients;
known second- or third-degree atrioventricular (AV) block. Special
warnings and precautions for use: Treatment with lacosamide has
been associated with dizziness which could increase the occurrence
of accidental injury or falls. Therefore, patients should be
advised to exercise caution until they are familiar with the
potential effects of the medicine. Prolongations in PR interval
with lacosamide have been observed in clinical studies. Cases with
second- and third-degree AV block associated with lacosamide
treatment have been reported in post-marketing experience.
Lacosamide should be used with caution in patients with known
conduction problems or severe cardiac disease such as a history of
myocardial infarction or heart failure. Caution should especially
be exerted when treating elderly patients as they may be at an
increased risk of cardiac disorders or when lacosamide is used in
combination with products known to be associated with PR
prolongation. Second-degree or higher AV block has been reported in
post-marketing experience. In the placebo-controlled trials of
lacosamide in epilepsy patients, atrial fibrillation or flutter
were not reported; however, both have been reported in open-label
epilepsy trials and in post-marketing experience. Patients should
be made aware of the symptoms of second-degree or higher AV block
(e.g. slow or irregular pulse, feeling of lightheadedness and
fainting) and of the symptoms of atrial fibrillation and flutter
(e.g. palpitations, rapid or irregular pulse, shortness of breath).
Patients should be counseled to seek medical advice should any of
these symptoms occur. Suicidal ideation and behavior have been
reported in patients treated with antiepileptic agents. Therefore
patients should be monitored for signs of suicidal ideation and
behaviors and appropriate treatment should be considered. Patients
(and caregivers of patients) should be advised to seek medical
advice should signs of suicidal ideation or behavior emerge. The
solution for infusion contains sodium, which should be taken into
consideration for patients on a controlled sodium diet. Effects on
ability to drive and use machines: Lacosamide may have minor to
moderate influence on the ability to drive and use machines.
Lacosamide treatment has been associated with dizziness and blurred
vision. Accordingly patients should be advised not to drive a car
or to operate other potentially hazardous machinery until they are
familiar with the effects of lacosamide on their ability to perform
such activities. Laboratory abnormalities: Abnormalities in liver
function tests have been observed in controlled trials with
lacosamide in adult patients with partial-onset seizures who were
taking 1-3 concomitant antiepileptic drugs. Elevations of ALT to
greater to or equal than 3XULN occurred in 0.7% (7/935) of
lacosamide patients and 0% (0/356) of placebo patients. Multiorgan
Hypersensitivity Reactions: Multiorgan hypersensitivity reactions
have been reported in patients treated with some antiepileptic
agents. These reactions are variable in expression but typically
present with fever and rash and can be associated with involvement
of different organ systems. Potential cases have been reported
rarely with lacosamide and if multiorgan hypersensitivity reaction
is suspected, lacosamide should be discontinued. Undesirable
effects: The most common adverse reactions (greater to or equal
than 10%) are dizziness, headache, diplopia, and nausea. Other
common adverse reactions (greater to or equal than 1% less than
10%) are depression, confusional state, insomnia, balance disorder,
coordination abnormal, memory impairment, cognitive disorder,
somnolence, tremor, nystagmus, hypoesthesia, dysarthria,
disturbance in attention, vision blurred, vertigo, tinnitus,
vomiting, constipation, flatulence, dyspepsia, dry mouth, pruritus,
rash, muscle spasms, gait disturbance, asthenia, fatigue,
irritability, injection site pain or discomfort (specific to
solution for infusion), irritation (specific to solution for
infusion), fall, and skin laceration. Refer to the European Summary
of Product Characteristics for other adverse reactions and full
prescribing information. Date of revision: 15 November, 2011.
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000863/WC500050338.pdf
(Accessed 18 October, 2011).
Further Information
Andrea Levin, Senior Manager, Communications & PR, CNS, UCB,
Inc.
T 770.970.8352
M 404.483.7329
Andrea.levin@ucb.com
Dana Gulick
Cooney/Waters Group
T 212.886.2227 / M 917.216.6268
DGulick@cooneywaters.com
About UCB
UCB, Brussels, Belgium ( www.ucb-usa.com ) is a global
biopharmaceutical company focused on the discovery and development
of innovative medicines and solutions to transform the lives of
people living with severe diseases of the immune system or of the
central nervous system. With more than 8,500 people in about 40
countries, the company generated revenue of EUR 3.2 billion in
2010. UCB is listed on Euronext Brussels (symbol: UCB).
Forward-looking statements
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.
(1) http://epilepsyfoundation.org/aboutepilepsy/
(2) http://epilepsyfoundation.org/aboutepilepsy/treatment/index.cfm
SOURCE UCB, Inc.
Web Site: http://www.ucb.com
Posted: December 2011
