2018年8月25日，美国FDA宣布批准Biocodex公司研发的Diacomit(stiripentol)上市，与氯巴占（clobazam）联合使用，治疗2岁以上Dravet综合征患者的癫痫发作。值得一提的是，这也是美国FDA批准的第31款新药。
  Dravet综合征又称为婴儿严重肌阵挛性癫痫（Severe Myoclonic Epilepsy of infancy， SMEI）。它是一种罕见的难治性癫痫综合征，发病率约为1/15700。80%的患者在SCN1A基因上携带基因突变。患者的癫痫发病年龄早，在出生后第一年里就会出现与发烧相关的癫痫，而且发作频率高，持续时间长，对儿童发育和智力的影响严重。
  目前对Dravet综合征的治疗手段非常有限，患者需要接受持续不断的护理，这会对患者及其家庭的生活质量产生严重影响。Dravet综合征患者可能因为癫痫发作时间过长，癫痫导致的事故，或癫痫发作时的突然死亡而去世，目前患者的死亡率为15-20%。患者和他们的父母迫切需要创新疗法来改善他们的生活质量。
  Stiripentol是Biocodex公司研发的用于治疗癫痫的抗惊厥药物。该药物的化学结构与其它已知抗惊厥药物不同。它已经在欧盟、加拿大和日本获得批准与丙戊酸钠（valproate）和氯巴占一起治疗Dravet综合征患者。美国FDA也在2008年授予了它用于治疗Dravet综合征的孤儿药资格。
  在两项多中心，含安慰剂对照的随机双盲临床试验中，总计64名患者接受了stiripentol或安慰剂的治疗，这些患者同时都服用丙戊酸钠和氯巴占。这两项试验的主要终点为患者的缓解率，定义为在接受8周治疗后患者的全身性阵挛性或强直-阵挛性癫痫发作频率与基线水平相比，降低超过50%的人数比例。
  试验结果表明stiripentol的疗效显着高于安慰剂。在第一项临床试验中，71%接受stiripentol治疗的患者的症状得到缓解，对照组的缓解率为5%。在第二项临床试验中，stiripentol组和对照组的缓解率分别为67%和9.1%。
  与对照组相比，stiripentol能够将患者的全身性阵挛性或强直-阵挛性癫痫发作频率降低43%，而且25%的患者在试验过程中没有出现全身性阵挛性或强直-阵挛性癫痫发作。
Diacomit Approved for the Treatment of Dravet Syndrome
The Food and Drug Administration (FDA) has approved Diacomit (stiripentol; Biocodex) for the treatment of seizures associated with Dravet syndrome in patients aged ≥2 years taking clobazam.
Diacomit was eva luated in 2 multicenter, placebo-controlled, double-blind, randomized studies (Study 1 and Study 2). Eligible patients were aged 3 years to <18 years with Dravet syndrome and had to be inadequately controlled on clobazam and valproate. After a 1-month baseline period, patients were randomized to either Diacomit or placebo, in addition to their treatment with clobazam and valproate.
The primary efficacy endpoint for both studies was the rate of responders, defined as a patient who had ≥50% decrease in the frequency (per 30 days) of generalized clonic or tonic-clonic seizures during the double-blind treatment period vs the 1-month baseline period.
In Study 1 (N=41), 71% of Diacomit-treated patients were responders vs 5% in the placebo group (P <.0001), while in Study 2 (N=23), 67% of Diacomit-treated patients were responders vs 9.1% in the placebo arm (P <.0094). Treatment with Diacomit was also superior to placebo for the reduction in mean frequency of generalized clonic or tonic-clonic seizures.
The exact anticonvulsant mechanism of Diacomit is unknown but possible actions include direct effects mediated through the gamma-aminobutyric acid (GABA)A receptor; indirect effects may involve inhibition of CYP450 activity with resulting increase in blood levels of clobazam and its active metabolite.
Somnolence, decreased appetite, agitation, ataxia, weight loss, hypotonia, nausea, tremor, dysarthria, and insomnia were the most common adverse events reported with Diacomit.
Diacomit will be available as 250mg and 500mg strength capsules in 60-count bottles and as fruit-flavored powder packets for oral suspension in 60-count cartons.