美国FDA批准新药CINVANTI（aprepitant）注射式乳剂上市
近日，Heron Therapeutics公司宣布，美国FDA批准其新药CINVANTI（aprepitant）注射式乳剂上市，在接受高度致吐性癌症化疗的患者中预防和治疗相关的恶心和呕吐。
CINVANTI是一款底物P/神经激肽-1受体拮抗剂，也是唯一一款用于该适应症的无聚山梨醇酯80静脉注射型配方。在两项关键的随机、交叉的生物等效性试验中，研究人员确定了CINVANTI的疗效。此外，与EMEND IV（活性成分也为aprepitant）相比，CINVANTI的副作用更小。基于这两项试验的结果，美国FDA也于今日批准它上市。
值得一提的是，CINVANTI上市后，Heron Therapeutics是唯一一家能够针对化疗诱发的恶心与呕吐的两大机制的公司。其另一款新药SUSTOL是血清素-3受体拮抗剂，针对的是另一条通路。
“化疗诱发的恶心和呕吐在肿瘤患者群体内有着高度未满足的医疗需求，我们的目标是涵盖5整天。神经激肽-1受体拮抗剂被推荐给高度致吐性癌症化疗患者作为常规疗法，也推荐给中度致吐性癌症化疗患者。这有望让CINVANTI造福更多患者，避免化疗诱发的恶心和呕吐，使他们能继续化疗疗程。” Tennessee Oncology的首席执行官Jeffrey F. Patton博士说道。
“CINVANTI和SUSTOL都能显著减少化疗引起的恶心和呕吐，而且有着两种互补的机制，”Heron的首席执行官Barry D. Quart博士说道：“在一年多的时间里获得美国FDA的第二项批准是Heron的重要成就，我们将继续推进第三款重要产品HTX-011。按计划，我们将在2018年递交给FDA审核。”
由于化疗诱发的恶心和呕吐为患者带来了极大不适，也会影响他们的治疗。我们祝贺这款有着巨大应用价值的新药问世，也期待它能造福更多患者！
Cinvanti (aprepitant) Injectable
Indication
CINVANTI is a substance P/neurokinin-1 (NK1) receptor antagonist, indicated in adults, in combination with other antiemetic agents, for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin and nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC).
Limitations of Use: CINVANTI has not been studied for treatment of established nausea and vomiting.
Important Safety Information
Contraindications
CINVANTI is contraindicated in patients with hypersensitivity to any of the components of CINVANTI.
Concurrent use of pimozide with CINVANTI is contraindicated.
Warnings and Precautions
Clinically Significant CYP3A4 Drug Interactions
Aprepitant is a substrate, weak-to-moderate (dose-dependent) inhibitor, and an inducer of CYP3A4.
• Use with other drugs that are CYP3A4 substrates may result in increased plasma concentration of the concomitant drug.
–Use of pimozide with CINVANTI is contraindicated due to the risk of significantly increased plasma concentrations of pimozide, potentially resulting in prolongation of the QT interval, a known adverse reaction of pimozide.
• Use of CINVANTI with strong or moderate CYP3A4 inhibitors (e.g., ketoconazole, diltiazem) may increase plasma concentrations of aprepitant and result in an increased risk of adverse reactions related to CINVANTI.
• Use of CINVANTI with strong CYP3A4 inducers (e.g., rifampin) may result in a reduction in aprepitant plasma concentrations and decreased efficacy of aprepitant.
Hypersensitivity Reactions
Serious hypersensitivity reactions, including anaphylaxis and anaphylactic shock, have been reported with fosaprepitant, a prodrug of aprepitant, and with oral aprepitant. Symptoms including flushing, erythema, dyspnea, hypotension and syncope have been reported. If symptoms occur, discontinue CINVANTI. Do not reinstate if symptoms occur with first time use.
Decrease in INR with Concomitant Warfarin
Co-administration of CINVANTI with warfarin, a CYP2C9 substrate, may result in a clinically significant decrease in the International Normalized Ratio (INR) of prothrombin time. Monitor the INR in patients on chronic warfarin therapy in the 2-week period, particularly at 7 to 10 days, following initiation of CINVANTI with each chemotherapy cycle.
Risk of Reduced Efficacy of Hormonal Contraceptives
The efficacy of hormonal contraceptives may be reduced during administration of and for 28 days following the last dose of CINVANTI. Advise patients to use effective alternative or back-up methods of non-hormonal contraception during treatment with CINVANTI and for 1 month following administration of CINVANTI or oral aprepitant, whichever is administered last.
Use in Specific Populations
Avoid use of CINVANTI in pregnant women as alcohol is an inactive ingredient for CINVANTI. There is no safe level of alcohol exposure in pregnancy.
Adverse Reactions
The most common adverse reactions with the 3-day oral aprepitant regimen in conjunction with MEC (≥1% and greater than standard therapy) were fatigue and eructation.
The most common adverse reactions with the single-dose intravenous fosaprepitant regimen in conjunction with HEC were generally similar to that seen in prior HEC studies with oral aprepitant. In addition, infusion site reactions (3%) occurred.
The most common adverse reactions with single-dose CINVANTI (≥2%) were headache and fatigue.
参考资料：
[1] Heron Therapeutics Announces U.S. FDA Approval of CINVANTI?（aprepitant）Injectable Emulsion for the Prevention of Acute and Delayed Chemotherapy-Induced Nausea and Vomiting（CINV）
[2] Heron Therapeutics官方网站
首款！FDA批准罕见病新药
今日，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。”
参考资料：
[1] FDA approves treatment for rare genetic enzyme disorder
[2] Ultragenyx Pharmaceutical官方网站