Non clinical development process and advantages of new antiepileptic drug buvasetam

Epilepsy is one of the highest incidence rate of neurological diseases. Over 50 million people worldwide have epilepsy. The incidence rate in developed countries is about 40-70/10 million per year. In the current treatment, about 2 / 3 of epileptic patients do not have seizures, but for the other 1 / 3 of epileptic patients, although there are several kinds of antiepileptic drugs (AEDs) available, they are still not well controlled. Therefore, in the field of epilepsy treatment, we are always looking forward to the emergence of more effective new drugs.

Levetiracetam (Lev) is the second generation of new antiepileptic drug (trade name Keppra) developed by UCB company of Belgium, which continues the traditional antiepileptic drugs such as carbamazepine, phenytoin and valproate ®)。 In December 1999, it was officially approved as adjuvant therapy for partial seizures in adults over 16 years old. In June 2005, the indications were extended to children over 4 years old. With its unique mechanism, levetiracetam has been proved to be effective and well tolerated in the treatment of adult partial seizures.

On January 14, 2016 and February 18, 2016, EMA and FDA approved the third-generation antiepileptic drug, brivaracetam (BRV), developed by UCB company in Belgium, with the trade name of briviact ®。 It is used in the treatment of epilepsy patients aged 16 and above with or without secondary generalized seizures.

The structures of BRV and LEV are very similar, both belong to pyrrolidone derivatives. Compared with the chemical structure of LEV, BRV has only one n-propyl group at the 4-position of pyrrolidine. The two drugs are similar to Gemini, so that when I first saw BRV, I mistakenly thought it was a pseudo innovative product, or a continuation product made by UCB company in order to continue the brilliant market brought by Lev products. No matter whether the judgment is correct or wrong or the motivation of research and development, there is still in-depth pharmacological mechanism research behind the emergence of BRV, This article is also to explore the unique discovery of such new antiepileptic drugs through the non clinical development process of BRV and the comparative advantages with LEV.