百时美PD-1抑制剂Opdivo欧美监管收获好消息

近日，在美国和欧盟，百时美施贵宝Opdivo的监管审查都传来了好消息。在美国，FDA已接受Opdivo的生物制品许可申请（BLA），同时将进行优先审查，并已指定处方药用户收费法（PDUFA）目标日期为2015年3月30日。而且FDA已授予Opdivo治疗黑色素瘤的突破性疗法认定。

在欧盟，欧洲药品管理局（EMA）已接受审查Opdivo治疗晚期黑色素瘤的上市许可申请（MAA）。同时，EMA下属人用医药产品委员会（CHMP）已授予Opdivo MAA加速评估，该加速评估将使Opdivo审查时间缩短2个月时间。

此前，业界预测，尽管百时美Opdivo于2015年才能获得FDA批准上市，但该药有望用作黑色素瘤的一线治疗；而默沙东Keytruda适应症为黑色素瘤的二线或三线治疗。尽管Keytruda率先在美国上市，但Opdivo适用范围的起点将超过Keytruda，适用人群更广，因此尽管晚上市半年，Opdivo仍有望反超Keytruda。

目前，默沙东和百时美也正在积极推进各自PD-1抑制剂的其他临床项目。百时美Opdivo的临床项目是一个大型全球性项目。目前，百时美正在超过35个临床试验中评估Opdivo作为单药或组合疗法用于各种类型肿瘤的治疗，包括非小细胞肺癌（NSCLC）、黑色素瘤，肾细胞癌（RCC）、头颈癌、成胶质细胞瘤及非霍奇金淋巴瘤等。在美国，FDA于2013年授予Opdivo治疗NSCLC、黑色素瘤、RCC的快车道地位。2014年4月，百时美施贵宝启动向FDA滚动提交Opdivo用于预治疗鳞状细胞NSCLC的监管申请，预计将于年底完成提交。2014年5月，FDA授予Opdivo治疗非霍奇金淋巴瘤的突破性疗法认定。

英文原文：Bristol-Myers Squibb Announces Multiple Regulatory Milestones for Opdivo (nivolumab) in the U.S. and European Union

——FDA accepts for priority review the Biologics License Application for previously treated advanced melanoma, based on data from first Phase 3 randomized trial of a PD-1 immune checkpoint inhibitor; agency grants second breakthrough therapy designation for Opdivo

——European Medicines Agency validates the marketing authorization application for advanced melanoma; accelerated assessment also granted

PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) today announced multiple regulatory milestones for Opdivo (nivolumab), an investigational PD-1 immune checkpoint inhibitor, in the U.S. and European Union. In the U.S., the Food and Drug Administration (FDA) has accepted for priority review the Biologics License Application (BLA) for previously treated advanced melanoma and the Prescription Drug User Fee Act (PDUFA) goal date for a decision is March 30, 2015. The FDA also granted Opdivo Breakthrough Therapy status for this indication. In the European Union, the European Medicines Agency (EMA) has validated for review the Marketing Authorization Application (MAA) for Opdivo in advanced melanoma. The application has also been granted accelerated assessment by the EMA’s Committee for Medicinal Products for Human Use (CHMP).

“The filing acceptance and validation of our Opdivo applications by the FDA and EMA represent significant steps forward in our commitment to delivering innovative immuno-oncology treatments to patients with cancer around the world,” said Michael Giordano, MD, senior vice president, Head of Oncology Development, Bristol-Myers Squibb. “Additionally, the Breakthrough Therapy Designation and the accelerated assessment for advanced melanoma underscore our focus on developing treatments for diseases in which a significant unmet medical need remains.”

About the U.S. Biologics License Application

The U.S. BLA is based on data from CheckMate -037, a multinational, multicenter, randomized open-label Phase 3 trial evaluating Opdivo compared to the physician’s choice of either dacarbazine (DTIC) or carboplatin/paclitaxel in patients with unresectable or metastatic melanoma who have been previously treated with Yervoy and, if BRAF-mutation positive, a BRAF inhibitor. Interim data from CheckMate -037 will be highlighted at an ESMO 2014 Congress press briefing on September 29 in the morning and presented during the Presidential Symposium at 4 p.m. CEST (Abstract #LBA3_PR).

In the U.S., priority review status is granted for applications for drugs that treat a serious condition and, if approved, would be a significant improvement in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications. Breakthrough Therapy Designation, according to the FDA, is intended to expedite the development and review of drugs for serious or life-threatening conditions. The criteria for this designation require preliminary clinical evidence that demonstrates that the drug may have substantial improvement on at least one clinically significant endpoint over available therapy.

About the E.U. Marketing Authorization Applications

The MAA submitted to the EMA in advanced melanoma is also supported by data from CheckMate -037. Accelerated assessment procedure may be requested for medicinal products of major interest from the point of view of public health and, in particular, from the point of view of therapeutic innovation. The acceptance of accelerated assessment by the CHMP could shorten the review time of Opdivo in advanced melanoma by approximately two months.

About Opdivo

Cancer cells may exploit “regulatory” pathways, such as checkpoint pathways, to hide from the immune system and shield the tumor from immune attack. Opdivo is an investigational, fully-human PD-1 immune checkpoint inhibitor that binds to the checkpoint receptor PD-1 (programmed death-1) expressed on activated T-cells.

Bristol-Myers Squibb has a broad, global development program to study Opdivo in multiple tumor types consisting of more than 35 trials – as monotherapy or in combination with other therapies – in which more than 7,000 patients have been enrolled worldwide. Among these are several potentially registrational trials in non-small cell lung cancer (NSCLC), melanoma, renal cell carcinoma (RCC), head and neck cancer, glioblastoma and non-Hodgkin lymphoma.

In 2013, the FDA granted Fast Track designation for Opdivo in NSCLC, melanoma and RCC. In April 2014, the company initiated a rolling submission with the FDA for Opdivo in third-line pre-treated squamous cell NSCLC and expects to complete the submission by year-end. The FDA granted its first Breakthrough Therapy Designation for Opdivo in May 2014 for the treatment of patients with Hodgkin lymphoma after failure of autologous stem cell transplant and brentuximab. On July 4, Ono Pharmaceutical Co. announced that Opdivo received manufacturing and marketing approval in Japan for the treatment of patients with unresectable melanoma, making Opdivo the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world.

Bristol-Myers Squibb has proposed the name Opdivo (pronounced op-dee-voh), which, if approved by health authorities, will serve as the trademark for nivolumab.

About Advanced Melanoma

Melanoma is a form of skin cancer characterized by the uncontrolled growth of pigment-producing cells (melanocytes) located in the skin. Metastatic melanoma is the deadliest form of the disease, and occurs when cancer spreads beyond the surface of the skin to the other organs, such as the lymph nodes, lungs, brain or other areas of the body. The incidence of melanoma has been increasing for at least 30 years. In 2012, an estimated 232,130 melanoma cases were diagnosed globally. Melanoma is mostly curable when treated in its early stages. However, in its late stages, the average survival rate has historically been just six months with a one-year mortality rate of 75 percent, making it one of the most aggressive forms of cancer.