VIMPAT - VIMPAT - CT 6048 - English version

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Introduction VIMPAT 50 mg film-coated tablet Box of 14 (CIP: 388 295-7) Box of 56 (CIP: 388 296-3) Box of 168 (CIP: 573 617-7) VIMPAT 100 mg film-coated tablet Box of 14 (CIP: 388 298-6) Box of 56 (CIP: 388 299-2) Box of 168 (CIP: 573 618-3) VIMPAT 150 mg film-coated tablet Box of 14 (CIP: 388 300-0) Box of 56 (CIP: 388 301-7) Box of 168 (CIP: 573 620-8) VIMPAT 200 mg film-coated tablet Box of 14 (CIP: 388 302-3) Box of 56 (CIP: 388 304-6) Box of 168 (CIP: 573 621-4) VIMPAT 15 mg/ml oral solution Bottle of 200 ml (CIP: 388 307-5) Bottle of 465 ml (CIP: 388 308-1) VIMPAT 10 mg/ml solution for infusion Box of 1 bottle (CIP: 388 309-8) Posted on Jun 06 2011 Active substance (DCI) lacosamide NEUROLOGIE - NOUVEAU MEDICAMENT Pas d’avantage clinique démontré par rapport aux traitements disponibles dans les crises d’épilepsie partielle. VIMPAT est indiqué en association à d’autres antiépileptiques dans le traitement des crises partielles, avec ou sans généralisation secondaire, chez des patients âgés de 16 ans et plus.Après 12 semaines de traitement, le pourcentage de répondeurs (fréquence des crises réduite d’au moins 50 %) a été plus élevé avec VIMPAT qu’avec placebo. Cette augmentation varie de 14,7 à 20 % selon les études.VIMPAT existe sous forme de comprimés à 50, 100, 150 et 200 mg, de sirop dosé à 15 mg/ml et de solution pour perfusion dosée à 10 mg/ml.Pour en savoir plus, téléchargez la synthèse ou l'avis complet ci-dessous ATC Code N03AX18 Laboratory / Manufacturer UCB PHARMA SA VIMPAT 50 mg film-coated tablet Box of 14 (CIP: 388 295-7) Box of 56 (CIP: 388 296-3) Box of 168 (CIP: 573 617-7) VIMPAT 100 mg film-coated tablet Box of 14 (CIP: 388 298-6) Box of 56 (CIP: 388 299-2) Box of 168 (CIP: 573 618-3) VIMPAT 150 mg film-coated tablet Box of 14 (CIP: 388 300-0) Box of 56 (CIP: 388 301-7) Box of 168 (CIP: 573 620-8) VIMPAT 200 mg film-coated tablet Box of 14 (CIP: 388 302-3) Box of 56 (CIP: 388 304-6) Box of 168 (CIP: 573 621-4) VIMPAT 15 mg/ml oral solution Bottle of 200 ml (CIP: 388 307-5) Bottle of 465 ml (CIP: 388 308-1) VIMPAT 10 mg/ml solution for infusion Box of 1 bottle (CIP: 388 309-8) Posted on Jun 06 2011

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• Publié par: haute-autorite-sante-maladies-systeme-nerveux
• Publié le: 04 mars 2009
• Nombre de lectures: 22
• Licence : En savoir +
  Paternité, pas d'utilisation commerciale, partage des conditions initiales à l'identique
• Langue: English

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  The legally binding text is the original French version  

TRANSPARENCY COMMITTEE   OPINION   4 March 2009   VIMPAT 50 mg film-coated tablet Box of 14 (CIP: 388 295-7)   Box of 56 (CIP: 388 296-3)   Box of 168 (CIP: 573 617-7)     VIMPAT 100 mg film-coated tablet Box of 14 (CIP: 388 298-6)   Box of 56 (CIP: 388 299-2)   Box of 168 (CIP: 573 618-3)     VIMPAT 150 mg film-coated tablet Box of 14 (CIP: 388 300-0)   Box of 56 (CIP: 388 301-7)   Box of 168 (CIP: 573 620-8)     VIMPAT 200 mg film-coated tablet Box of 14 (CIP: 388 302-3)   Box of 56 (CIP: 388 304-6)   Box of 168 (CIP: 573 621-4)     VIMPAT 15 mg/ml oral solution Bottle of 200 ml (CIP: 388 307-5) Bottle of 465 ml (CIP: 388 308-1)   VIMPAT 10 mg/ml solution for infusion Box of 1 bottle (CIP: 388 309-8)     Applicant: UCB PHARMA SA   Lacosamide  ATC : N03AX18   List I   Date of Marketing Authorisation: 29 August 2008 (centralised MA)     Reason for request: Inclusion on the list of medicines reimbursed by National Health Insurance (apart from boxes of 168 and the solution for infusion) and approved for hospital use.     Medical, Economic, and Public Health Assessment Division

 

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CHARACTERISTICS OF THE MEDICINAL PRODUCT

  1.1. Active ingredient Lacosamide    1.2. Indication “VIMPAT is indicated as adjunctive therapy in the treatment of partial-onset seizures with or without secondary generalisation in patients with epilepsy aged 16 years and older.”   1.3. Dosage “VIMPAT must be taken twice a day. The recommended starting dose is 50 mg twice a day which should be increased to an initial therapeutic dose of 100 mg twice a day after one week.   Depending on response and tolerability, the maintenance dose can be further increased by 50 mg twice a day every week, to a maximum recommended daily dose of 400 mg (200 mg twice a day).   VIMPAT may be taken with or without food.   In accordance with current clinical practice, if VIMPAT has to be discontinued, it is recommended this be done gradually (e.g. taper the daily dose by 200 mg/week).   Injection: VIMPAT therapy can be initiated with either oral or i.v. administration. The solution for infusion is infused over a period of 15 to 60 minutes twice daily. VIMPAT solution for infusion can be administered i.v. without further dilution. Conversion to or from oral and i.v. administration can be done directly without titration. The total daily dose and twice daily administration should be maintained. There is experience with twice daily infusions of VIMPAT up to 5 days.   Use in patients with renal impairment: No dose adjustment is necessary in mildly and moderately renally impaired patients (CL CR >30 ml/min). A maximum dose of 250 mg/day is recommended for patients with severe renal impairment (CL CR ≤30 ml/min) and in patients with endstage renal disease. For patients requiring haemodialysis a supplement of up to 50% of the divided daily dose directly after the end of haemodialysis is recommended. Treatment of patients with end-stage renal disease should be made with caution as there is little clinical experience and accumulation of a metabolite (with no known pharmacological activity). In all patients with renal impairment, the dose titration should be performed with caution (see SPC).   Use in patients with hepatic impairment: No dose adjustment is needed for patients with mild to moderate hepatic impairment. The dose titration in these patients should be performed with caution considering co-existing renal impairment. The pharmacokinetics of lacosamide has not been evaluated in severely hepatic impaired patients (see SPC).   Use in elderly (over 65 years of age): No dose reduction is necessary in elderly patients. The experience with lacosamide in elderly patients with epilepsy is limited. Age associated decreased renal clearance with an increase in AUC levels should be considered in elderly patients (see ‘Use in patients with renal impairment’ above and SPC).   Paediatric patients: VIMPAT is not recommended for use in children and adolescents below the age of 16 as there is no data on safety and efficacy in these age groups.”

 

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2 SIMILAR MEDICINAL PRODUCTS 2.1. ATC Classification (2008) N : Nervous system   N03 : Antiepileptics N03A : Antiepileptics N03AX  antiepileptics: Other N03AX18 : Lacosamide   2.2. Medicines in the same therapeutic category VIMPAT (lacosamide) is indicated as adjunctive therapy in the treatment of partial-onset seizures with or without secondary generalisation in patients with epilepsy aged 16 years and older   Medicines having the same indications as VIMPAT “as adjunctive therapy, in the treatment of partial-onset seizures”: ·  Oral route   -GABITRIL (tiagabine) from 12 years of age - LYRICA(pregabalin), adult patients, -indicated only when other appropriate combination therapies (vigabatrin)  SABRIL have proved inadequate or to be poorly tolerated, -ZONEGRAN (zonisamide), adult patients.   Medicines indicated in the treatment of "partial-onset seizures", but as adjunctive therapy and as monotherapy: · Oral route: 3rd generation antiepileptics: - EPITOMAX (topiramate), as monotherapy after the failure of previous treatment, as an adjunct to other antiepileptics when the latter are insufficiently effective, - KEPPRA (levetiracetam). - LAMICTAL (lamotrigine), - NEURONTIN (gabapentin),   - TRILEPTAL (oxcarbazepine). 2nd generation antiepileptics: - DEPAKINE (sodium valproate), - TEGRETOL (carbamazepine).   1st generation antiepileptics: -DIHYDAN (phenytoin), - GARDENAL (phenobarbital), -MYSOLINE (primidone). · Parenteral route: - DEPAKINE injectable (valproic acid), - DILANTIN (phenytoin), - GARDENAL (phenobarbital), - KEPPRA (levetiracetam), - PRO-DILANTIN (fosphenytoin).   2.3. Medicines with a similar therapeutic aim All products indicated in the treatment of epilepsy.

 

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3 ANALYSIS OF AVAILABLE DATA   3.1.Efficacy  The efficacy and tolerance of oral VIMPAT, as adjunctive therapy with other antiepileptics in partial-onset epilepsy have been evaluated in three randomised double-blind studies versus placebo over a period of 12 weeks.   The aim of the studies was to demonstrate superiority for VIMPAT in terms of patient responder rates. - Study SP667 1 (phase IIb): VIMPAT 200 mg/day, 400 mg/day, and 600 mg/day versus placebo in 415 adult patients, - Study SP754 (phase III): VIMPAT 400 and 600 mg/day versus placebo in 402 patients aged 16 years or over, - Study SP755 (phase III): VIMPAT 200 and 400 mg/day versus placebo in 477    patients aged 16 years or over. These studies included a total of 1308 patients who had failed on at least two different antiepileptics.    Three open follow-up studies (SP615, SP756, and SP774) are currently ongoing. An interim analysis of these 3 studies which was made in 2006 was provided.     Two other studies (SP645 and SP658) not examined in this opinion compared the kinetic parameters after single infusions of VIMPAT 200 mg over 30 min and 60 min versus VIMPAT 200 mg in tablet form. The pharmacokinetic characteristics of VIMPAT 200 mg administered by intravenous infusion over 30 or 60 min were comparable to those of a single oral administration of VIMPAT 200 mg in tablet form.   3.1.1. Study SP667 Methodology: phase IIb study, the main aim of which was to demonstrate the superior efficacy of oral VIMPAT (200, 400, and 600 mg/day) administered in combination with 1 or 2 antiepileptics in comparison with placebo in 415 patients with non-controlled partial-onset seizures with or without secondary generalisation who were followed up for 12 weeks.     Inclusion criteria: patients between 18 and 65 years of age with:   - partial-onset seizures 2 : simple (accompanied by motor signs) and/or complex, with or without secondary generalisation, - continued seizures for at least two years in spite of treatment with at least two different antiepileptics, - on average, four partial-onset seizures per 28 days with a seizure-free period of no longer than 21 days in the 8 weeks leading up to their inclusion, - on stable treatment with antiepileptics (≤2) for at least four weeks, in combination or not in combination with vagal nerve stimulation therapy.   Treatment: - VIMPAT 200 mg/day, n=107, - VIMPAT 400 mg/day, n=107, - VIMPAT 600 mg/day, n=105, - Placebo, n=96.   All the patients continued their antiepileptic therapy (1 to 2 concomitant treatments) throughout the study.

                                             1 Ben-Menachem E et al. Efficacy and safety of oral lacosamide as adjunctive therapy in adults with partial-onset 2  .selipEesruzi07 ;48:1epsia 20 eDifen 03-871.  ttog inrdcoacd anoitanretni eh   l classification of partial-onset epilepsy of 1981    

 

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Note: The ANAES [National Health Accreditation and Assessment Agency] 2004 consensus conference on the “Prise en charge des épilepsies partielles pharmaco-résistantes” [Management of drug-resistant partial-onset epilepsy] recommends “avoiding the use of a combination of more than two antiepileptics in the treatment of partial-onset epilepsy (Level C)”   .   After randomisation, the patients were included in a 6-week titration phase during which doses were gradually increased. At the end of this phase, the patients were included in a "maintenance" phase of treatment at a stable dose for 12 weeks. A phase of gradual discontinuation of treatment or of reduction to 200 mg/day was implemented in patients included in the open follow-up phase.     Primary endpoint: patient responder rate, defined as the percentage of patients with an at least 50% reduction in seizure frequency after 12 weeks of treatment 3  (maintenance phase compared to inclusion status).     Secondary endpoints, including:   reduction in median frequency of seizures over a period of 28 days.   RESULTS:     Primary endpoint:ITT analysis (cf. Table 1)   On inclusion, the characteristics of the patients were comparable overall. The results of the VIMPAT 600 mg/day group will not be presented in this opinion, as they are not for a dosage that has been validated by MA.   Table 1: Responder rate after 12 weeks' treatment   Pl ebo  VIMPAT VIMPAT   a = c 200 mg/day 400 mg/day  n 96  n = 107 n 107 = Responder rate (at least 50% reduction in the 21.9% (21/96) 32.7%(35/107)41.1%(44/107) frequency of seizures)   - Difference from placebo    10.8% 19.2% - OR [95% CI]    1.7 2.5 [0.9;3.3] [1.3;4.6] - p versus placebo NS < 0.01   After 12 weeks of treatment, the responder rate was higher in the VIMPAT 400 mg/day group (41.4%) than in the placebo group (21.9%), p < 0.01. On the other hand, no significant difference was observable between VIMPAT 200 mg/day and placebo.     Secondary endpoint: The median frequency of seizures over a period of 28 days was reduced by 28.4% [11.3, 42.2] (p=0.0023) in the VIMPAT 400 mg/day group in comparison with placebo. On the other hand, no significant difference was observable between VIMPAT 200 mg/day and placebo; seizures reduced by 14.6% [-3.2, 29.4], NS.

                                             3  The primary endpoint was analysed in two ways, depending on the registration authority. For the EMEA, the   analysis was carried out in terms of the percentage of responders, defined as those with an at least 50% reduction in the number of seizures, a criterion which was used to calculate the necessary case rate. For the FDA, the evaluation was based on the reduction of the frequency of seizures over a period of 28 days. This criterion was considered as a secondary endpoint by the EMEA.  

 

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  3.1.2. Studies SP754 and SP755   Method: randomised, double-blind, placebo-controlled phase III studies, the main aim of which was to demonstrate the superior efficacy of oral VIMPAT administered in combination with 1 or 3 antiepileptics in comparison with placebo in patients with non-controlled or inadequately controlled partial-onset epileptic seizures with or without secondary generalisation who were followed up for 12 weeks.     The methodology and aim of these studies were identical to those of the above-mentioned study SP 667. The dosages investigated and the number of concomitant antiepileptic treatments (1 to 3) were different:     Treatment: Study SP754: total ITT population (n=402)   - VIMPAT 400 mg/day, n=201, - VIMPAT 600 mg/day, n=97, - Placebo, n=104.   Study SP755: total ITT population (n=477)   - VIMPAT 200 mg/day, n=160,   - VIMPAT 400 mg/day, n=158, - Placebo, n=159.   All the patients continued their antiepileptic therapy (1 to 3 concomitant treatments) throughout the studies. Note: The ANAES [National Health Accreditation and Assessment Agency] 2004 consensus conference on the “Prise en charge des épilepsies partielles pharmaco-résistantes” [Management of drug-resistant partial-onset epilepsy] recommends “avoiding the use of a combination of more than two antiepileptics in the treatment of partial-onset epilepsy” (Level C)   .   In these studies, after randomisation, the patients were included in a titration phase (6 weeks in study SP754 and 4 weeks in study SP755) during which doses were gradually increased. At the end of this phase, the patients were included in a "maintenance" phase of treatment at a stable dose for 12 weeks. A phase of gradual discontinuation of treatment or of reduction to 200 mg/day was implemented in patients included in the open follow-up phase.     Inclusion criteria: The inclusion criteria were the same as those of study SP667, with two main differences:   - patients between 16 and 70 years of age; - on stable treatment with antiepileptics (≤3) for at least 4 weeks, in combination or not in combination with vagal nerve stimulation therapy.   Primary endpoint : patient responder rate, defined as the percentage of patients with an at least 50% reduction in seizure frequency after 12 weeks of treatment 3  phase (maintenance compared to inclusion).   Secondary endpoints, including:   reduction in median frequency of seizures over a period of 28 days.   RESULTS:   On inclusion, the characteristics of the patients were comparable overall.    

 

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Primary endpoint:ITT analysis(cf. Table 2)   The results of the VIMPAT 600 mg/day group will not be presented in this opinion, as they are not for a dosage that has been validated by MA.   Table 2: Responder rate after 12 weeks' treatment      a P t e  l r e c a e s n t t   a 5 g 0 e %  o  r f  e p d a u ti c e ti n o t n s     in w   i t t h h  e a   n  Placeb VIMPAT 40 V 0 I   M m P g/ A d T a   o 200  mg/day y   frequency of seizures      Study SP 754 n= 104 -  n= 201       -Responder rate    18.3% (19/104) 38.3% (77/201) - Difference from placebo   20% - OR [95% CI]   2.8 [1.6;5.0] ; - p versus placebo p=0.0004 Study SP 755 n= 159 n= n= 160 158       -Responder rate    25.8% (41/159) 35.0% (56/160)40.5% (64/158) - Difference from placebo   9.2% 14.7% - OR [95% CI]    2.0 [1.2 ; 3.2]1.6 [1.0 ; 2.6] - p versus placebo   NS p=0.006   In study SP754, after 12 weeks of treatment, the responder rate was higher in the VIMPAT 400 mg/day group (38.3%) than in the placebo group (18.3%), p=0.0004.   In study SP755 after 12 weeks of treatment, the responder rate was higher in the VIMPAT 400 mg/day group (40.5%) than in the placebo group (25.8%), p=0.006. On the other hand, no significant difference was observable between VIMPAT 200 mg/day and placebo.     Secondary endpoint: In study SP754, over a period of 28 days, the median frequency of seizures was reduced in the VIMPAT 400 mg/day group in comparison with placebo: difference of -21.6% [6.3, 34.5], p=0.0078.   In study SP755, over a period of 28 days, the median frequency of seizures was reduced: - by 15% [1.4 ; 26.8], p=0.0325, under VIMPAT 400 mg/day in comparison with placebo - by 14.4% [2.2 ; 25.1], p=0.0223, under VIMPAT 200 mg/day in comparison with placebo.   3.1.3. Open follow-up studies (SP615, SP756, and SP774) Three open follow-up studies (SP615, SP756, and SP774) are currently ongoing, the results for which are from an interim analysis made in 2006. In total, 978 patients were included. The mean VIMPAT dosage administered to the patients was 400 mg/day.   After one year of treatment, 80% of the patients remained in the study. In study SP615, after 2.5 years of treatment, the rate of patients remaining in the study was 52%. The responder rate after 6 months of treatment was 43.1% in study SP756 and 47.1% in study SP774 and 47.4% in study SP615 after 1 year of treatment.   3.2. Adverse effects In these 3 studies, tolerance was analysed on the basis of 1,308 patients treated with VIMPAT or placebo for a mean duration of exposure of 96 days. Among these patients, 61.9% of the VIMPAT group and 35.2% of the placebo group showed at least one adverse effect, usually mild to moderate in intensity.    

 

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In study SP667, 42% (41/97) of the patients in the placebo group, 55% (59/107) of the patients in the VIMPAT 200 mg/day group, and 59% (64/108) of the patients in the VIMPAT 400 mg/day group showed adverse effects; the most frequent were:   dizziness: 9/97 patients (9%) in the placebo group versus 23/107 (21%) in the - VIMPAT 200 mg/day group versus 24/108 patients (22%) in the VIMPAT 400 mg/day group,   - ataxia: 3/97 (3%) versus 4/107 (4%) versus 12/108 (11%),    -  versus 9/107 (8%) versus 13/108 (12%),headache: 5/97 (5%)   - nausea: 8/97 (8%) versus 6/107 (6%) versus 15/108 (14%),   - drowsiness: 6/97 (6%) versus 8/107 (7%) versus 12/108 (11%),   - diplopia: 1/97 (1%) versus 4/107 (4%) versus 11/108 (10%).     In study SP754, 47.1% (49/104) of the patients in the placebo group, 75.5% (154/204) of the patients in the VIMPAT 400 mg/day group showed adverse effects; the most frequent were: - diplopia: 3/104 (2.9%) versus 20/204 (9.8%),   - visual disturbances: 3/104 (11%) versus 22/204 (10.8%),   - nausea: 2/104 (1.9%) versus 20/204 (9.8%),   - dizziness: 8/104 (7.7%) versus 79/204 (38.7%),   - drowsiness: 6/104 (5.8%) versus 18/204 (8.8%).     In study SP755, 30.1% (49/163) of the patients in the placebo group, 36.8% (60/163) of the patients in the VIMPAT 200 mg/day group, and 47.8% (76/159) of the patients in the VIMPAT 400 mg/day group showed adverse effects; the most frequent were:   (1.2%) versus 12/163 (7.4%) versus 16/159 (10.1%),diplopia: 2/163  - - nausea: 2/163 (1.2%) versus 8/163 (4.9%) versus 8/159 (5%),   - tiredness: 6/163 (3.7%) versus 7/163 (4.3%) versus 9/159 (5.7%),   - dizziness: 7/163 (4.3%) versus 16/163 (9.8%) versus 25/159 (15.7%),   - headache: 6/163 (3.7%) versus 11/163 (6.7%) versus 9/159 (5.7%).     In these three studies the dropout rate due to adverse effects was 12.2% in the VIMPAT group and 1.6% in the placebo group. Dizziness was the most frequent adverse effect.     According to the SPC, “The use of lacosamide is associated with dose-related increase in the PR interval. Adverse reactions associated with PR interval prolongation (e.g. atrioventricular block, syncope, bradycardia) may occur. In epilepsy patients the incidence rate of reported first degree AV Block is uncommon, 0.7%, 0%, 0.5% and 0% for lacosamide 200 mg, 400 mg, 600 mg or placebo, respectively. No second or higher degree AV Block was seen in lacosamide treated patients. The incidence rate for syncope is uncommon and did not differ between lacosamide treated epilepsy patients (0.1%) and placebo treated epilepsy patients (0.3%).” VIMPAT is the subject of a risk management plan.   Studies SP616 and SP757 evaluated the tolerance of VIMPAT solution for infusion versus VIMPAT oral tablet. Overall, the adverse effects observed in these studies and their frequencies were comparable between the two groups and similar to those observed in studies SP667, SP754, and SP755 mentioned above.     3.3. Conclusion The efficacy and tolerance of VIMPAT in combination with other antiepileptics (1 to 3) were evaluated in 3 placebo-controlled, randomised studies (SP667, SP 754, and SP 755) carried out in patients with partial-onset epilepsy with or without secondary generalisation (4 seizures a month on average) and continued seizures for at least two years in spite of treatment with at least two different antiepileptics.  

 

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In these three studies, after 12 weeks of treatment, the percentage of patients responding (defined as an at least 50% reduction in seizure frequency) was higher with VIMPAT 400 mg/day than with placebo. It was, respectively, in these studies   - difference of 19.2% (OR = 2.5 ; 95CI [1.3; 4.6]; p<0.01).41.1% vs 21.9%, a    38.3% vs 18.3%, a difference of 20% (OR = 2.8 ; 95% CI [1.6; 5.0]; p=0,0004). - - 40.5% vs 25.8%, a difference of 14.7% (OR 2.0, 95% CI [1.2; 3.2]; p=0,006).   No significant difference was observable between VIMPAT 200 mg/day and placebo.     The adverse events observed most frequently in these studies were as follows: nausea, dizziness, diplopia, headache, drowsiness.     No study providing a comparison with another antiepileptic is available. No study of monotherapy is available.   Bioequivalence between VIMPAT 200 mg tablets and VIMPAT 200 mg for injection infused over a period of 30 to 60 min has been established.     4 TRANSPARENCY COMMITTEE CONCLUSIONS   4.1. Actual benefit   Epilepsy is a serious disease. Epileptic seizures are symptoms of a highly heterogeneous array of disorders. Epilepsy, defined as – generally spontaneous – repetition of these seizures over the medium and long term, can markedly impair the patient's quality of life.     VIMPAT is a symptomatic treatment which is indicated in combination with other antiepileptics in the treatment of partial-onset epileptic seizures with or without secondary generalisation. In the therapeutic strategy for epilepsy, VIMPAT represents an additional therapeutic way.     The efficacy/adverse effects ratio of these proprietary medicinal products is high.   There are drug-therapeutic alternatives to these proprietary products.   Public health benefit: Partial epilepsy is a common disease, and the repetition of the seizures in some patients can markedly impair their quality of life. Overall, it represents a moderate public health burden. The burden in respect of the population of patients suffering from partial epilepsy after failure of monotherapy is also moderate. There is a public-health need insofar as drug-resistant partial epilepsy remains common and causes substantial disability. On the basis of the available data (trials versus placebo, improvement of responder rate), it is not possible to know whether VIMPAT will have an additional effect on morbidity and on the quality of life of the treated population in comparison with existing therapies. Thus it is not possible to know whether VIMPAT, in this indication, will meet the identified public-health need. Consequently, in the current state of knowledge and in view of the fact that other therapies are already available, this proprietary product is not expected to have any public health benefit in this indication.   The actual benefit of these proprietary products is substantial.  

 

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4.2. Improvement in actual benefit (IAB)   As adjunctive therapy in the treatment of partial-onset seizures with or without secondary generalisation in patients with epilepsy aged 16 years and older, VIMPAT does not provide an improvement in actual benefit (IAB V) in comparison with the other available therapies. It nevertheless represents a useful additional therapeutic way in the management of these patients.     4,5 4.3. Therapeutic use The antiepileptic treatment chosen depends on the characteristics of the epileptic syndrome and the specifics of the patient. In the management of newly or recently diagnosed partial-onset epilepsy, monotherapy is the recommended first-line approach, using, in particular, carbamazepine or valproic acid on account of their superior risk/benefit ratio in comparison with phenytoin and phenobarbital (recommendation level C). Optimal-dose carbamazepine therapy must be used at least once in such monotherapy (expert consensus). The other treatment alternatives are gabapentin, lamotrigine, and levetiracetam.     In the event of failure (inadequate response, adverse effects resulting in discontinuation of treatment) in spite of an adequate dosage and adequate compliance with the treatment, replacement monotherapy is gradually introduced. At least two different monotherapies must be attempted. In the treatment of partial-onset epileptic seizures, carbamazepine and sodium valproate are the standard therapies. Oxcarbazepine, lamotrigine, and gabapentin are indicated as first-line monotherapy or in combination. Since these recommendations, levetiracetam has also been granted MA (2005) as first-line monotherapy.     The use of a combination of more than 2 antiepileptic medicines is not recommended (Level C).   Addition of a second antiepileptic is recommended if the response to the preceding monotherapies is insufficient. VIMPAT is thus a therapeutic tool that supplements existing treatments.   4.4. Target population The target population of VIMPAT is patients aged 16 years or over with partial-onset epileptic seizures with or without secondary generalisation requiring treatment with a combination of antiepileptics.    It can be estimated from the following data: - The number of epilepsy patients in France is estimated to be between 350,000 and 400,000 4 ; - Partial-onset seizures account for approximately 60% of all epileptic seizures 4,6 , i.e. 210,000 to 240,000 patients; -to 80% of cases; thus 20 to 30% of is effective in approximately 70  Monotherapy patients may receive VIMPAT in combination with other antiepileptics. The target population of VIMPAT can be estimated at between 42,000 and 72,000 patients.       4.5. Transparency Committee recommendations The Transparency Committee recommends inclusion on the list of medicines reimbursed by National Health Insurance (boxes of 14 and 56 tablets and oral solution) and on the list of

                                             4  conference. Prise en charge des épilepsies partielles pharmaco-résistantes [Management of drug- Consensus resistant partial-o i ANAES 2004.   5 /2082.00ofn 0/ 3ts de Nenseioll蠖 Ces Ege dlag itnoileniuedNa  pe tesn .]yspel   6 AW r te H esua gnan .eVsroirulogoei rintCo. syepilepalupop fo noitubive riptDescal. o  folygmeoipedi itnob-sades utyd from Rochester, Minnessota. Mayo Clin Proc 1996;73:576-86.  

 

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medicines approved for use by hospitals and various public services (all presentations) in the indications and at the dosages in the marketing authorisation.   Packaging: appropriate for the prescription conditions     Reimbursement rate: 65%      

 

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