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Nya data: Signifikant förbättrad anfallskontroll vid epilepsi

Pressmeddelande   •   Jul 03, 2009 09:48 CEST

En summering av kliniska data visar att det nya epilepsiläkemedlet Vimpat (lakosamid) som tilläggsbehandling för patienter med okontrollerad partiell epilepsi gav signifikant ökad anfallskontroll, ökad anfallsfrihet i underhållsfasen och förbättrad livskvalitet och funktion (2, 3). Resultaten presenteras i dagarna på den internationella epilepsikonferensen, IEC 2009 i Budapest.

Studieresultaten bygger på tre kliniska fas II/III studier, designade på liknande sätt, där man undersökt doserna 200, 400, 600* mg/dag. Vimpat (lakosamid) reducerade signifikant partiella epilepsianfall jämfört med placebo när läkemedlet användes som tilläggsbehandling till andra antiepileptika (epilepsiläkemedel) (1, 3, 5). 47 svenska patienter från Sahlgrenska Universitetssjukhuset, Karolinska Institutet och Universitetssjukhuset i Linköping deltog i två av studierna.

Vimpat gav en dosberoende ökad effekt för de primära effektvariablerna (frekvens av partiella anfall och 50% responder rate) vid alla undersökta doser samt vid den sekundära effektvariabeln 75% responder rate upp till 400 mg/dag (3, 5).

Patienterna som svarade på Vimpat (200, 400, 600* mg/dag) rapporterade ett förbättrat hälsotillstånd och ökad livskvalitet (4, 5).

- 60% av alla som lever med epilepsi har partiella epilepsianfall. Runt en tredjedel förblir okontrollerade trots att de har provat behandling med ett antal olika epilepsiläkemedel. De här studierna stödjer Vimpats effekt i att reducera partiella epilepsianfall och förbättra anfallskontrollen när läkemedlet används som tilläggsbehandling till befintliga antiepileptika. Detta i en population som till större delen består av patienter som behandlas med två eller tre andra antiepileptika men trots det är okontrollerade, säger professor Elinor Ben-Menachem, Professor i neurologi och epilepsi och klinisk prövare, Institutionen för Neurovetenskap vid Göteborgs Universitet.

Vimpat är i Europa indicerat som tilläggsbehandling vid behandling av partiella epilepsianfall med eller utan sekundär generalisering för patienter över 16 år.

*Dosen 600 mg/dag är ej godkänd i Europa.

För mer information, vänligen kontakta
Barbro Fernegård, skandinavisk produktchef, UCB Nordic, 070-275 23 50, barbro.fernegard@ucb.com
Helene Meinild, Medical Advisor CNS, UCB Nordic, +45 25 60 03 02,  helene.meinild@ucb.com
Elinor Ben-Menachem, Professor, Institutet för klinisk Neurovetenskap vid Göteborgs Universitet, Elinor.Ben-Menachem@neuro.gu.se

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MER BAKGRUND PÅ ENGELSKA

Summary of Lacosamide Data Presented at the 2009 IEC Congress, Budapest, Hungary

Adjunctive lacosamide significantly reduced partial-onset seizures at all doses* studied (3)
A pooled analysis of three Phase II/III trials showed that lacosamide significantly reduced partial-onset seizures compared with placebo at all doses studied (200, 400, 600* mg/day).

Lacosamide (400 and 600* mg) significantly reduced partial-onset seizure frequency and improved 50% responder rates compared to placebo in all individual studies (p<0.05 for all analyses).

To further evaluate 200 mg/day lacosamide, a meta-analysis was conducted that showed a significant difference from placebo for both primary efficacy endpoints (p<0.05).

The pooled analysis comprised 1,294 subjects randomised to lacosamide (200 mg/day, n=267; 400 mg/day, n=466; 600* mg/day, n = 202) and 359 randomised to placebo, who had at least one post-baseline efficacy assessment.

Adjunctive lacosamide improved seizure freedom rates and ≥75% responder rates with increasing dose* (5)
Pooled analysis from Phase II/III clinical trials showed a dose-responsive trend for seizure freedom rates with an increasing dose* of lacosamide (2.7%, 3.3% and 4.8% for 200, 400 or 600* mg/day vs 0.9% placebo) in a patient population predicted to have a poor response to treatment.

Seizure freedom was defined as the proportion of enrolled patients who completed the study and remained seizure free throughout a 12-week maintenance period.

The percentage of patients experiencing a 75% or greater reduction in partial-onset seizure frequency from the baseline to maintenance period was also evaluated.

A dose response was evident in 75% responder rates between lacosamide 200 and 400 mg/day. Increasing the dose to 600* mg/day did not increase the response, possibly due to the fixed-dose trial design, combined with lower tolerability observed at doses of lacosamide above 400mg/day.

Patients who responded to lacosamide showed improvements across all measured areas of patient functioning (4)
A pooled analysis from three Phase II/III trials evaluating lacosamide (200, 400 or 600* mg/day) showed patients responding to lacosamide experienced self-reported improvements in quality of life, patient function and health status.

In patients stratified by treatment group and level of clinical response the impact of lacosamide on patient's lives was assessed via secondary endpoints including mean Quality of Life Inventory In Epilepsy (QOLIE-31) and Seizure Severity Scale (SSS) score changes from baseline, and distribution of Patient Global Impression of Change (PGIC) (Phase III trials only) at last assessment.

Responders with more than 50% seizure reduction in the overall patient population and lacosamide treatment groups experienced significant improvements in QOLIE-31 and SSS scores from baseline (p<0.05 for all comparisons of responders to non-responders). Largest improvements were obtained for quality of life score including QOLIE-31 seizure worry and social functioning, as well as SSS overall score.For the PGIC analysis more than 80% of lacosamide responders reported an improved health status.

The QOLIE-31 analysis comprised 1,046 patients including 738 subjects randomised to lacosamide (PGIC: 829 total including 575 lacosamide; SSS: 823 total including 571 lacosamide).

Adjunctive lacosamide was generally well-tolerated when combined with up to three concomitant AEDs (7)
A pooled analysis of data from three Phase II/III trials, comprising 944 subjects randomised to lacosamide, showed that lacosamide was generally well-tolerated compared with placebo, when combined with 2-3 concomitant AEDs.

The most commonly reported treatment-emergent adverse events, in ≥10% of the lacosamide group and greater than placebo, were dizziness (31% vs. 8%), headache (13% vs. 9%), nausea (11% vs. 4%) and diplopia (11% vs. 2%) (6).

Most adverse events were mild to moderate in intensity and some were dose-related (1).

* The recommended maintenance dose of lacosamide is 200 mg to400 mg/day. The 600 mg/day dose of lacosamide is not approved by the EMEA and FDA. In clinical trials, the overall efficacy of the 600 mg/day dose was similar to the 400 mg daily dose, and was associated with a higher rate of CNS and gastrointestinal-related adverse reactions (1, 6).

Lacosamide clinical trials program
Analyses of pooled data from one phase II and two phase III double-blind, placebo-controlled trials, evaluated the efficacy and safety of lacosamide (200 mg, 400 mg and 600* mg/day) as adjunctive therapy in more than 1,308 adults with uncontrolled partial-onset seizures with or without secondary generalisation (1, 3).

Seizure reduction was measured by the primary endpoints: median percent reduction in seizure frequency per 28 days from baseline to maintenance period; and the 50% responder rate, defined as the proportion of patients experiencing a 50% or greater reduction in partial-onset seizure frequency per 28 days from baseline to the maintenance period (3).

At baseline, most patients (85%) were uncontrolled on 2-3 AEDs, and had high seizure frequencies which are predictors for a poor response to treatment (7, 8, 9, 10).

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Referenser

1. VIMPAT® Summary of Product Characteristics.
2. Beyreuther BK, Freitag J, Heers C et al. Lacosamide: A Review of Preclinical Properties. CNS Drug Reviews 2007; 13: 21-42.
3. Ben-Menachem E, Chung S, Rudd D, Hebert D and Doty P. Evaluation of Lacosamide Efficacy in Subjects with Partial-Onset Seizures Across the Dose Range Used in Phase II/III Clinical Trials. Poster Presentation, 28th International Epilepsy Congress 28 June - 2 July 2009.
4. De La Loge, C, Cramer J, Borghs S, Mueller K, Eggert A, Doty P. Improvement in patient-reported outcomes seen in patients responding to lacosamide: Pooled QOLIE-31, SSS and PGIC data from 3 Phase II/III clinical trials. Poster Presentation, 28th International Epilepsy Congress 28 June - 2 July 2009.
5. French J, Brodie M, Hebert D, Isojarvi J, Doty P. Evaluation of Seizure Freedom and 75% Responder Rates with Lacosamide in Subjects with Partial-Onset Seizures in Phase II/III Clinical Trials. Poster Presentation, 28th International Epilepsy Congress 28 June - 2 July 2009.
6. VIMPAT® Prescribing Information (US).
7. Gil-Nagel A, Biton V, Fountain N, Rosenow F, Hebert D, Doty P. The Safety and Tolerability of Lacosamide in Randomized, Double-Blind, Placebo-Controlled Phase II/III Trials. Poster Presentation, 28th International Epilepsy Congress 28 June - 2 July 2009.
8. Ben-Menachem E, et al. Efficacy and Safety of Oral Lacosamide for the Treatment of Partial Onset Seizures as Adjunctive Therapy in Adults with Partial Onset Seizures.  Epilepsia 2007;48(7):1308-1317.
9. Callaghan BC, Anand K, Hesdorffer D, Hauser WA, French JA. Likelihood of seizure remission in an adult population with refractory epilepsy. Ann Neurol 2007; 62(4) 382-389.
10. Hitiris N et al Predictors of pharmacoresistant epilepsy. Epilepsy Research 2007; 75: 192-196.