—PD-1抑制剂Opdivo (nivolumab)获美国FDA加速批准的新药
2014年12月22日，美国食品和药品监管局[FDA]授权加速批准Opdivo(nivolumab)，一种对其他药物不再反应的有不能切除或转移(晚期)黑色素瘤患者的新治疗。
黑色素瘤是在美国.第五位最常见类型癌。它在黑色素瘤细胞形成，它发展皮肤色素。美国国家癌症研究所估计本年度76,100美国人将被诊断有黑色素瘤和9,710将死于此病。
Opdivo通过抑制细胞上PD-1蛋白作用，阻断机体免疫系统来自黑色素瘤肿瘤攻击。Opdivo是意向为以前曾用易普利姆玛[ipilimumab]治疗患者和，对黑色素瘤患者其肿瘤表达基因突变被称为BRAF V600，为用易普利姆玛和一种BRAF抑制剂使用后治疗。
FDA的药品评价和研究中心血液学和肿瘤学产品室主任Richard Pazdur，医学博士说：“Opdivo是自2011年被FDA批准的第七个新黑色素瘤药物。”“根据我们肿瘤免疫学和分子学通路增加了解继续发展和批准新颖治疗正在改变对严重和危及生命疾病治疗范式。”
对黑色素瘤其他FDA-批准的治疗包括易普利姆玛(2011)，聚乙二醇干扰素α-2b(2011)，威罗菲尼[vemurafenib](2011)，达拉非尼[dabrafenib](2013)，曲美替尼[trametinib](2013)和pembrolizumab (2014)。Opdivo正在比处方药用户收费目标日期2015年3月30日提前3个月被批准，这个日期是监管局计划完成其申请审评的日期。
FDA授权Opvido突破性治疗指定，优先审评和孤儿产品指定因为承办单位分别通过初步临床证据证实药物可能提供超出可得到治疗实质上改进；在申请递交时药物某种严重情况的治疗中安全性或有效性中有潜在的，显著改进；和药物是意向治疗某种罕见疾病。
Opvido正在FDA的加速批准程序下被批准，该程序允许批准某个治疗严重或危及生命疾病根据临床数据显示药物对一个替代性终点有效应可能合理地预测对患者临床获益。这个程序提供患者较早得到鼓舞人有前途新药而公司进行附加临床试验验证药物的获益。
Opdivo的疗效在120例临床试验有不能切除或转移黑色素瘤参加者中被证实。结果显示接受Opdivo参加者32%有其肿瘤皱缩(客观反应率)，在经历肿瘤皱缩参加者约三分之一这个效应持续超过6个月。
在268例用Opdivo治疗参加者和102例用化疗治疗参加者的总体试验人群中评价Opdivo的安全性。最常见药物的副作用是皮疹，瘙痒，咳嗽，山呼吸道感染，和液体潴留(水肿)。最严重副作用是严重免疫介导副作用涉及健康器官，包括肺，结肠，肝，肾和计算产生腺体。.
Opdivo是由普林斯顿，新泽西州的施贵宝销售。
批准日期： 2014年12月22日；公司：施贵宝公司、

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm427716.htm
ristol-Myers Squibb：Opdivo(nivolumab)
Company: Bristol-Myers Squibb
Brand Name: Opdivo or BMS-936558 , nivolumab, Opdivo Generic Name: nivolumabMolecule Type: Biologic
Opdivo (nivolumab) Demonstrates High Overall Response Rate of 87% for Treatment of Relapsed or Refractory Hodgkin Lymphoma
--Safety and tolerability results, a primary objective in the study, were consistent with other Opdivo trials
--Results from another arm of this Phase 1 study show promising activity with Opdivo in non-Hodgkin Lymphoma
Bristol-Myers Squibb Company (NYSE:BMY) today announced positive results from a cohort of patients in its ongoing Phase 1b trial (CheckMate -039) which evaluated PD-1 immune checkpoint inhibitor, Opdivo (nivolumab), in patients with relapsed or refractory hematological malignancies (n=23). Results showed high levels of response in patients with relapsed or refractory classical Hodgkin Lymphoma (HL), with an overall response rate of 87% (n=20) and stable disease in 13% (n=3). These findings were published today in The New England Journal of Medicine (NEJM) and highlighted in the press briefing on Saturday, December 6 during the 56th annual meeting of the American Society for Hematology (Abstract #289).
In patients with HL, initial treatment typically consists of chemotherapy and/or radiation therapy, followed by an autologous stem cell transplant (ASCT) if the disease recurs. For those who relapse within one year after receiving a standard of care like ASCT, the median survival is only 1.3 years after progression.
"Despite the current treatment landscape, this patient population is still experiencing relatively short-lived responses that often result in relapse. So, there is a critical need to identify new options that can improve outcomes during the course of their care," said Philippe Armand, M.D., Ph.D, medical oncologist, Dana-Farber Cancer Institute and Associate Professor, Department of Medicine, Harvard Medical School. "These findings with Opdivo are incredibly encouraging because they show that an immuno-oncology approach with a check point blockade has the potential to be applied to lymphomas."
CheckMate -039 results support the first Breakthrough Therapy Designation for Opdivo, granted in May 2014 by the U.S. Food and Drug Administration (FDA) for the treatment of patients with HL after failure of autologous stem cell transplant and brentuximab.
"Bristol-Myers Squibb has a long standing commitment to the treatment of hematologic cancers, and we continue to advance potential treatment options for this patient population through our leadership in Immuno-Oncology," said Michael Giordano, senior vice president, Head of Development, Oncology, Bristol-Myers Squibb. "These new data from Opdivo represent the next step towards our goal of identifying therapies that can transform the standard of care across a variety of cancer types."
On Monday, December 8, additional results from CheckMate -039 will be highlighted in a separate oral presentation (Abstract #291) that could support the potential of Opdivo to treat patients with relapsed or refractory non-Hodgkin lymphoma. This ongoing Phase 1 trial is also exploring the combination of Opdivo and Yervoy in hematologic malignancies. Data from that arm of the study will be published at a later date.
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 CheckMate -039
CheckMate -039 is an ongoing Phase 1 dose escalation study of patients with relapsed and refractory hematological malignancies, which includes a cohort evaluating Opdivo in patients with HL after failure of autologous stem cell transplant and brentuximab. The cohort includes 23 patients who were treated with Opdivo 3 mg/kg at week one, week four and every two weeks until disease progression or complete response or for a maximum of two years. The primary endpoints included evaluating the safety and tolerability of Opdivo. Secondary endpoints included determining antitumor activity, characterizing Opdivo pharmacokinetics and immunogenicity, and assessing PD-L1 and PD-L2 expression as a predictive biomarker.
In the trial, 87% (n=20) achieved an overall response, with 17% (n=4) achieving complete response and 70% (n=16) a partial response. The remaining patients, 13% (n=3), experienced stable disease. Of the patients who achieved a complete and partial response, 60% (n=12) had their first response within eight weeks (range: 3-39 weeks). Data from the study also showed a progression-free survival rate of 86% at 24 weeks, meaning patients lived six months longer without their disease worsening.
Safety results were reported in all patients treated in the study. Overall, drug-related adverse events of any grade were reported in 78% of patients (n=18), with the most common being rash (22%) and decreased platelet count (17%). Of these, Grade 3 adverse events occurred in 22% of patients (n=5). There were no treatment-related Grade 4 or 5 adverse events.
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 50 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 2012, 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 Opdivo Breakthrough Therapy Designation 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. On September 26, Bristol-Myers Squibb announced that the FDA accepted for priority review the Biologics License Application for previously treated advanced melanoma, and the Prescription Drug User Fee Act 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 for Opdivo in advanced melanoma. The application has also been granted accelerated assessment by the EMA's CHMP. The EMA also validated for review the MAA for nivolumab in NSCLC.
About Hodgkin Lymphoma
Hodgkin lymphoma (HL), also known as Hodgkin disease, is a cancer of the lymphatic system, which originates in the white blood cells. HL is one of two main types of lymphomas. The five-year survival rate for advanced HL is approximately 65 percent in the U.S. The median age of diagnosis is 38 in the U.S. This year, more than 9,100 new cases are estimated to be diagnosed with more than 1,100 deaths expected.
Immuno-Oncology at Bristol-Myers Squibb
Surgery, radiation, cytotoxic or targeted therapies have represented the mainstay of cancer treatment over the last several decades, but long-term survival and a positive quality of life have remained elusive for many patients with advanced disease.
To address this unmet medical need, Bristol-Myers Squibb is leading advances in the innovative field of immuno-oncology, which involves agents whose primary mechanism is to work directly with the body's immune system to fight cancer. The company is exploring a variety of compounds and immunotherapeutic approaches for patients with different types of cancer, including researching the potential of combining immuno-oncology agents that target different and complementary pathways in the treatment of cancer.
Bristol-Myers Squibb is committed to advancing the science of immuno-oncology, with the goal of changing survival expectations and the way patients live with cancer.
About the Bristol-Myers Squibb and Ono Pharmaceutical Collaboration
In 2011, through a collaboration agreement with Ono Pharmaceutical, Bristol-Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Bristol-Myers Squibb and Ono Pharmaceutical further expanded the companies' strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies - as single agents and combination regimens - for patients with cancer in Japan, South Korea and Taiwan.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global pharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol-Myers Squibb, visit www.bms.com, or follow us on Twitter at http://twitter.com/bmsnews.
Bristol-Myers Squibb Forward-Looking Statement
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that Opdivo will receive regulatory approval in the U.S. or, if approved, that it will become a commercially successful product. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2013 in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.