New data for Vimpat® (lacosamide) showed sustained efficacy for up to 5 years and improved seizure control when added to a broad range of antiepileptic drugs
(Thomson Reuters ONE) -
For the Attention of Accredited Medical Writers
Brussels, BELGIUM, June 29(th), 2010 at 1330 CET-New long term data showed that
Vimpat(®) (lacosamide) provided sustained reduction in seizure frequency for up
to five years when used as an add-on treatment for uncontrolled partial onset
seizures in adults with epilepsy.[1] In addition post-hoc exploratory analyses
showed that adjunctive lacosamide treatment reduced partial-onset seizure
frequency and improved responder rates when added to a broad range of
antiepileptic drugs (AEDs) including both traditional sodium channel-blocking
agents* and those that act on non-sodium channel-targets.[2],[3]( )These and
other data were presented this week at the 9(th) European Congress on
Epileptology (ECE), in Rhodes, Greece.( )
"The new data showed that lacosamide provided long-term additional partial-onset
seizure control when added to a broad range of AEDs and when current therapy was
not enough." said Dr Jacqueline French, Professor in the department of
Neurology, NYU Comprehensive Epilepsy Centre, U.S.
In addition, laboratory results of the first direct in-vitro comparison of
lacosamide with other AEDs were also presented at the Congress and provided
additional evidence of lacosamide's novel mode of action.[4]
In the European Union, Vimpat(®) (film-coated tablets, syrup, 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.[5] Vimpat(®) is approved in the U.S. as an add-on
therapy for the treatment of partial-onset seizures in people with epilepsy who
are 17 years and older, and is available as oral tablets, oral solution and as
an intravenous (IV) injection.[6] The maximum recommended daily dose for
Vimpat(®) in the European Union and the US is 400 mg/day.[5],[6]( ) Vimpat(®)
solution for infusion may be used when oral administration is temporarily not
feasible. Vimpat(® )has a novel mechanism of action that is different from all
currently available AEDs, although the precise mechanism by which Vimpat(®)
exerts its antiepileptic effect in humans is yet to be fully
elucidated.[5],[6],[7],[8]
About the Data
Vimpat(®) - sustained efficacy for up to 5 years[1](
)Long term sustained efficacy has been reported in patients with partial-onset
seizures who completed 1 to 5 years of adjunctive treatment with lacosamide.()
Pooled data from 1,327 patients who took part in double-blind trials and/or
corresponding open-label lacosamide trials were analyzed, and results for the
first three months of treatment were compared with those of the last three
months of treatment in cohorts completing 1, 3 and 5 years of therapy.
Median percent reductions in seizure frequency for the first 3 months of
treatment were 45.5%, 50.0% and 48.2% for the 1 (n=853), 3 (n=384) and 5 (n=67)
year cohorts, respectively. These results compared with 52.4%, 72.7% and 71.8%
during the last three months of treatment, demonstrating sustained effects over
time.
The proportion of patients achieving a >50% improvement in seizure frequency was
also sustained in each cohort, ranging from 45.0%-50.3% for the first 3 months
of treatment, compared to 51.8%-70.6% for the last 3 months.
Long-term efficacy of lacosamide for partial-onset seizures: An interim
evaluation of completer cohorts exposed to lacosamide for up to 5 years
French J, Ben-Menachem E( ), Isojarvi J, Hebert D, Doty P.
Platform session: Drug Therapy 29(th) June, 11.30 - 13.00
Vimpat(®) - additional efficacy when added to a broad range of AEDs[2],[3](
)Lacosamide reduced seizure frequency and improved responder rates in epilepsy
patients with uncontrolled partial seizures regardless of the type of AED they
were already taking.()
Of 1,308 patients who took part in phase II/III placebo-controlled lacosamide
trials, 82% were using at least one traditional sodium channel-blocking AED (eg,
lamotrigine, oxcarbazepine, carbamazepine or phenytoin). Patients could also be
taking other concomitant AEDs. In this group:
* Median percent reduction in seizure frequency per 28 days for lacosamide
200mg, 400mg and 600mg/day** was reduced by 33.3%, 39.0%, 42.7%
respectively, compared to 18.9% with placebo (p<0.01)
* 50% responder rates with lacosamide 200mg, 400mg and 600mg/day** compared to
placebo were 33.3% (p=0.06), 39.9% (p<0.01) and 42.4% (p<0.01) versus 22.7%
* The most common treatment-emergent adverse events (TEAEs) (> 10%) were
dizziness, headache, nausea, diplopia and vomiting.
Evaluation of lacosamide efficacy and safety as adjunctive therapy in patients
receiving traditional sodium channel blocking AEDs
Isojarvi J, Hebert D, Doty P, Zackheim J, Davies K, Sake J-K, Eggert-Formella A
Poster session: Drug therapy I, P230: 28(th) June, 13.30-14.30
In the 18% of patients taking only AEDs that act on non-sodium channel blocking
AEDs (eg, valproate, levetiracetam, topiramate, zonisamide, gabapentin,
pregabalin, phenobarbital, tiagabine and/or lorazepam):
* Median percent reduction in seizure frequency per 28 days for lacosamide
200mg, 400mg and 600mg/day** was reduced by 38.0% (p=0.11), 62.5% (p<0.01)
and 79.0% (p<0.01) compared with placebo (28.0%)
* 50% responder rates with lacosamide 200mg, 400mg and 600mg/day** compared to
placebo were 41.9% (p=0.2), 62.3% (p<0.01) and 79.2% (p<0.01) versus 25.0%
* Lacosamide was generally well-tolerated, with 8.6% of patients withdrawing
from treatment due to TEAEs. The most common TEAEs (> 10%, all lacosamide
doses combined) were dizziness (15.3%), headache (12.3%) and fatigue
(10.4%).
Lacosamide efficacy and safety in patients taking AEDs that act on non-sodium
channel targets
Sake J-K, Hebert D, Doty P, Zackheim J, Eggert-Formella A , Davies K, Isojarvi
J
Poster session: Drug therapy XI, P414: 29(th) June, 13.30-14.30
Vimpat(®) - novel mode of action[4](
)The precise mechanism by which lacosamide exerts its antiepileptic effect in
humans remains to be fully elucidated.[5],[6] Results of the first direct
comparison of lacosamide and other AEDs on voltage gated sodium channel
inactivation provided additional evidence of its novel mode of action.
In laboratory studies the selective effects of lacosamide on voltage gated
sodium channel slow inactivation parameters were compared to other AEDs that
target the sodium channel (carbamazepine, phenytoin, lamotrigine, zonisamide and
rufinamide). The study was performed in the N1E-115 mouse neuroblastoma cell
line expressing native voltage gated sodium channels.
The electrophysiological results showed that lacosamide produced a significant
and large change in neurophysiological parameters indicative of a selective
enhancement of the slow inactivation of voltage gated sodium channels, while no
such effect was seen with carbamazepine or zonisamide. Phenytoin, lamotrigine
and rufinamide modified slow inactivation parameters in different ways from
lacosamide.
Modulation of sodium channels is important for control of abnormal neuronal
activity in the brains of people with epilepsy, and inactivation can occur via
fast or slow mechanisms. While other sodium channel blocking AEDs act primarily
via fast inactivation, the novel effect of VIMPAT(®) through the selective
enhancement of slow inactivation is thought to control neuronal
hyperexcitability without affecting normal nerve function.[7],[9]
Comparative study of lacosamide with other sodium channel blocking antiepileptic
drugs on sodium current slow inactivation
Niespodziany I, Leclère N, Vandenplas C, Foerch P, Wolff C
Poster session: Drug therapy VI, P506: 30(th) June, 13.30-14.30
Other UCB-supported lacosamide studies presented at the 9(th) European Congress
on Epileptology included:
* A multicenter, open-label trial to assess the safety and tolerability of a
single intravenous loading dose of lacosamide followed by oral maintenance
as adjunctive therapy in patients with partial-onset seizures
Fountain NB, Krauss G, Isojarvi J, Dilley D, Doty P,Rudd GD
Poster session: Drug therapy XI, P416: 29(th) June, 13.30-14.30
* Pharmacokinetic evaluation of oral lacosamide in Phase II/III clinical
trials: a pooled analysis
Cawello W, Andreas J-O, Hebert D, Eggert-Formella A
Poster session: Drug therapy I, P227: 28(th) June, 13.30-14.30.
* Beta 1 Na+ channel subunit loss impairs the effects of CBZ but not
lacosamide on repetitive firing via differential effects on persistent Na+
currents
Uebachs( )M, Opitz( )T, Stoehr T( ), Niespodziany I, Wolff C, Beck H
Poster session: Drug therapy VI, P499: 30(th) June, 13.30-14.30
* For the post hoc exploratory analysis traditional sodium channel blocking
agents were lamotrigine, oxcarbazepine, carbamazepine or phenytoin.[2]
** The maximum recommended dose for VIMPAT(® )in the European Union and in the
U.S. is 400mg/day. The 600mg/day dose is not a recommended dose in the European
Union on in the U.S.[5],[6]( )
For further information
Eimear O'Brien, Associate Director, Global CNS Communications, UCB Group
T: +32 2 559 9271,eimear.OBrien(at)ucb-group.com
Andrea Levin, Public Relations Manager, CNS, UCB, Inc.
T: 770.970.8352,andrea.levin(at)ucb.com
Important safety information about Vimpat(®) in the European Union[5]
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. Vimpat(®) solution for infusion is an alternative for
patients when oral administration is temporarily not feasible.
Contraindications: Hypersensitivity to the active substance or to peanuts or
soya or to any of the excipients (tablet formulation only); 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. 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. Suicidal ideation and behaviour have been
reported in patients treated with anti-epileptic agents. Therefore patients
should be monitored for signs of suicidal ideation and behaviours and
appropriate treatment should be considered. Patients (and caregivers of
patients) should be advised to seek medical advice should signs of suicidal
ideation or behaviour emerge. Undesirable effects: The most common adverse
reactions (greater than 10 percent) are dizziness, headache, diplopia, and
nausea. Other common adverse reactions (1-10 percent) are depression,
confusional state, 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 and 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.
http://www.emea.europa.eu/humandocs/PDFs/EPAR/vimpat/emea-combined-h863en.pdf
(Updated June 2010)
Important safety information about Vimpat(®) in the U.S.[6]
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.
Vimpat(®) oral solution contains aspartame, a source of phenylalanine. A 200 mg
dose of Vimpat(®) oral solution (equivalent to 20mL) contains 0.32 mg of
phenylalanine. 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.
The most common adverse reactions occurring in ?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. Use in severe hepatic impairment
patients is not recommended.
Vimpat(®) is a Schedule V controlled substance.
Please see full prescribing information at http://www.vimpat.com/pdfs/PI.pdf.
(Accessed 28th May 2010)
Vimpat(®) is a registered trademark under license from Harris FRC Corporation.
About UCB
UCB, Brussels, Belgium (www.ucb.com) is a biopharmaceutical company dedicated to
the research, development and commercialization of innovative medicines with a
focus on the fields of central nervous system and immunology disorders.
Employing more than 9 000 people in over 40 countries, UCB produced revenue of
EUR 3.1 billion in 2009. UCB is listed on Euronext Brussels (symbol: UCB).
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.
References
[1] French( )J, Ben-Menachem( )E, Isojarvi( )J et al.( )Long-term efficacy of
lacosamide for partial-onset seizures: An interim evaluation of completer
cohorts exposed to lacosamide for up to 5 years. Presented at the 9(th) European
Congress on Epileptology, Rhodes, Greece. 27 June-1 July 2010
[2] Isojarvi( )J, Hebert( )D, Doty( )P et al. Evaluation of lacosamide efficacy
and safety as adjunctive therapy in patients receiving traditional sodium
channel blocking AEDs. Presented at the 9(th) European Congress on Epileptology,
Rhodes, Greece. 27 June-1 July 2010
[3] Sake( )J-K, Hebert( .)D, Doty( .)P( )et al. Lacosamide efficacy and safety
in patients taking AEDs that act on non-sodium channel targets. Presented at the
9(th) European Congress on Epileptology, Rhodes, Greece. 27 June-1 July 2010
[4] Niespodziany I, Leclère N, Vandenplas C, Foerch P and Wolff C. Comparative
study of lacosamide with other sodium channel blocking antiepileptic drugs on
sodium current slow inactivation. Presented at the 9(th) European Congress on
Epileptology, Rhodes, Greece. 27 June-1 July 2010
[5] Vimpat(®) European Summary of Product Characteristics
http://www.emea.europa.eu/humandocs/PDFs/EPAR/vimpat/emea-combined-h863en.pdf
(Updated June 2010)
[6] Vimpat(®) US Prescribing Information
http://www.vimpat.com/pdfs/PI.pdf
(Accessed 28(th) May 2010)
[7] Beyreuther BK, Freitag J, Heers C, Krebsfänger N, Scharfenecker U, Stöhr T.
Lacosamide: A review of preclinical properties. CNS Drug Reviews.
2007;13(1):21-42
[8] Errington AC, Stohr T, Heers C, Lees G. The investigational anticonvulsant
lacosamide selectively enhances slow inactivation of voltage-gated sodium
channels. Mol Pharmacol. 2008 Jan;73(1):157-69
[9] Ben-Menachem E. Lacosamide: an investigational drug for adjunctive treatment
of partial-onset seizures. Drugs Today 2008; 44: 35-40
For the pdf-version of this press release, please click on the link below:
[HUG#1428033]
Press release (PDF): http://hugin.info/133973/R/1428033/375587.pdf
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