Mepsevii(vestronidase alfa-vjbk)—为VII型粘多糖贮积症(MPS VII)新药
2017年11月16日,美国FDA宣布批准Ultragenyx Pharmaceutical 的新药Mepsevii(vestronidase alfa-vjbk)上市,治疗VII型粘多糖贮积症(MPS VII)。这是首款经美国FDA批准,治疗儿童和成人MPS VII患者的创新疗法。
MPS VII是一种极为罕见的遗传病,全球影响了不到150名患者,而且每一名患者的症状都有所不同。但绝大多数患者会有严重的骨骼异常,病情随着年龄增长不断加重。此外,患者还可能出现心脏瓣膜异常、肝脏脾脏增大、以及呼吸道狭窄等问题。根据病情严重程度的不同,一些患者会在婴儿期去世,而另一些则能活到青春期,甚至是成年期。对于这些患者来说,他们急需一种有效的治疗手段来挽救生命。
MPS VII的病理给了研究人员治疗的灵感。这种疾病属于溶酶体贮积症的一种,病因是由于患者体内缺乏足够的β-葡糖苷酸酶(β-glucuronidase)。因此,患者无法代谢特定的底物,造成有毒代谢产物在细胞中堆积,引起症状。今日获批的Mepsevii是一种酶替代疗法,能行使正常的酶活功能,帮助患者进行代谢,对症下药地治疗疾病。先前,这款创新疗法曾获得美国FDA颁发的孤儿药资格以及快速通道资格。
Mepsevii 的安全性与有效性在临床试验中得到了确认。一共有23名患者参与了这项研究,年龄跨度为5 个月到25岁。这些患者每2周接受每公斤体重4mg的Mepsevii 治疗,持续164周。
研究发现,在24周的治疗后,治疗组的6分钟行走测试结果比对照组多出18米。在最多达120周的后续跟进中,研究人员发现3名患者的病情得到了持续改善,剩下能参与行走测试的患者的病情也都稳定了下来。此外,两名患者的肺功能得到了改善。总体来看,如果没有治疗,就无法预期患者能出现这些改善。安全性上,Mepsevii 也没有带来严重的问题。最常见的副作用是输注部位的反应、腹泻、皮症、以及过敏。基于这些良好的结果,美国 FDA 也于今日批准该疗法上市。
“本次批准强调了FDA为罕见病患者提供疗法的承诺,”美国FDA药物评估和研究中心(CDER)药物评估III办公室的负责人Julie Beitz博士说道:“在今日的批准前,患有这种罕见遗传病的患者无药可用。”
Mepsevii Approved to Treat Rare Genetic Disease
The Food and Drug Administration (FDA) has approved Mepsevii (vestronidase alfa-vjbk) for the treatment of Mucopolysaccharidosis VII (MPS VII, Sly syndrome) in pediatric and adult patients. This enzyme replacement therapy is intended to replace the deficient lysosomal enzyme beta-glucuronidase in MPS VII patients.
The approval of Mepsevii was based on a clinical trial program that included 23 patients with MPS VII; the patients ranged in age from 5 months to 25 years. Patients received Mepsevii at doses up to 4mg/kg once every two weeks for up to 164 weeks. Efficacy was primarily assessed through the 6-minute walk test (6MWT) in 10 patients who could perform the test.
After 24 weeks, the mean difference in distance walked relative to placebo was 18 meters. Additional follow-up for up to 120 weeks suggested continued improvement in 3 patients and stabilization in the remaining 7 patients. After 120 weeks of exposure, 1 patient demonstrated a 21% improvement over baseline in forced vital capacity (FVC% predicted) on pulmonary function testing in addition to a 105 meter improvement in the 6MWT. Two other patients with baseline hepatosplenomegaly had reduction in liver volume (24% and 53%) and spleen volume (28% and 47%) after 36 weeks of Mepsevii treatment. The effect of Mepsevii on the central nervous system manifestations of MPS VII has not been determined
The most common side of effects of treatment include infusion site reactions, diarrhea, rash, and anaphylaxis.
Mepsevii is supplied as a carton containing one 10mg/5mL single-dose vial. It is expected to be available later this month.