美国加州圣地亚哥举行的北美地区癫痫会议上，德国Schwarz Pharma公司宣读了其口服lacosamide（Ⅰ）作为成人未控制的部分性惊厥的辅助治疗的Ⅲ期试验中安全性和疗效的阳性资料。（Ⅰ）200mg／日和（Ⅰ）400mg／日两组都显示比安慰剂组有统计学显著的和临床相关的改善。在过去用过三种不同的抗癫痫药仍不能控制的患者中同时加用（Ⅰ）后一般能很好耐受。

拉科酰胺（Lacosamide）是德国SchwarzBioSciences公司研发的治疗癫痫和神经性疼痛的药物。2008年9月欧盟批准UCB公司的拉科酰胺片上市，用于辅助治疗16岁及以上有或无继发性癫痫大发作患者的癫痫部分发作。2008年10月表示美国FDA已批准拉科酰胺上市作为一种辅助药物与其它药物联合用于癫痫部分性发作，商品名为Vimpat。Vimpat获准上市的有2种剂型：薄膜片（50 、100 、150和200 mg/片）、注射液（10 mg/mL,20ml/支），当患者不宜口服时可采用推注给药。
Lacosamide拉科酰胺（也称拉考沙胺,Vimpat）说明书 

Vimpat Approved in Europe

• Improved seizure control when added to other antiepileptic drugs (AEDs) (1)
• High long-term retention rate
• A dual mode of action

UCB announced on 12th January 2009 that the European Commission (EC) has approved Vimpat (lacosamide) 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 is the first new antiepileptic drug (AED) for partial-onset seizures in three years.

Epilepsy is a chronic neurological disorder affecting 50 million people worldwide. Approximately, 20-30% of people living with epilepsy have uncontrolled seizures or significant side effects secondary to medication highlighting the ongoing need for the development of new antiepileptic drugs (2).

Vimpat is an antiepileptic drug with a dual mode of action. The European Commission approval is based on data from three multicentre, randomised, placebo-controlled clinical trials that evaluated the efficacy and safety of Vimpat adjunctive treatment in over 1,300 partial-onset seizure patients. In these trials, Vimpat was shown to improve seizure control when added to a wide range of first and second generation AEDs. In addition, a long-term open trial where patients received Vimpat during a period ranging from 1 year to more than 30 months showed that the benefits were sustained over time (2).

Improved seizure control when added to other antiepileptic drugs (1)

One multicentre, double-blind, placebo-controlled trial included 485 patients (aged 16-70 years) with partial-onset seizures with or without secondary generalisation1. Most of these (87%) were taking two or more concomitant AEDs. Participants were randomised to placebo or lacosamide 200 or 400mg/day after an 8-week baseline period. Lacosamide was titrated over 4 weeks and maintained for 12 weeks.

The median percent reduction in seizure frequency over placebo was significant for lacosamide 200mg/day and 400mg/day (p<0.05 for both, Figure 1a).

Similarly, significantly more patients had their seizures reduced by half (50% responder rate) when treated with lacosamide 400mg/day compared with placebo (40.5% vs. 25.8%, p=0.01). (Figure 1b).

Adverse events that appeared dose-related included dizziness, nausea, and vomiting. Lacosamide did not affect mean plasma concentrations of concomitantly administered AEDs.

A dual mode of action (2)

While the precise mechanism by which Vimpat exerts its antiepileptic effect in humans remains to be fully elucidated, in preclinical studies Vimpat has been shown to modulate sodium channel activity differently compared with other sodium channel blocking antiepileptic drugs (AEDs).

Additionally, preclinical studies suggest that Vimpat binds to the collapsin response mediator protein-2 (CRMP-2), a phosphoprotein which is mainly expressed in the nervous system and is involved in neuronal differentiation and control of axonal outgrowth. The nature of the interaction between Vimpat and CRMP-2 is not completely known.

Conclusion

Professor Elinor Ben-Menachem, Clinical Trial Investigator, Department of Clinical Neuroscience, Goteborg University, Sweden said: "The novel mode of action of Vimpat makes it different from all other antiepileptic drugs currently available. Vimpat should be considered a valuable treatment option for adult patients with partial-onset seizures who need additional seizure control." (2)

1- Halász P, et al; on behalf of the SP755 Study Group. Epilepsia. 2009 Jan 17.
2- Data on file

Full prescribing information and references available from UCB (Pharma) Ireland Ltd. Telephone: (01) 4637395. MIMS Ireland Copyright®

 Posted in 06 New clinical evidence on 02 March 2009