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—Opdivo(Nivolumab Injection)获美国FDA扩展批准成为首个对肺癌有效的PD-1药物
2015年3月4日，美国食品和药品监管局(FDA)扩展批准使用Opdivo(nivolumab)治疗有晚期(转移)鳞状细胞非小细胞肺癌(NSCLC)用基于铂化疗或后有进展患者。
在美国肺癌是是癌症死亡的领先原因，在2014年有估计224,210例新诊断和159,260例死亡。肺癌的最常见型，NSCLC影响7/8肺癌患者，当在肺的细胞中癌形成时发生。
Opdivo通过抑制细胞通路被称为细胞上PD-1蛋白它阻断机体免疫系统攻击癌细胞起作用。Opdivo是意向为以前曾用基于铂化疗治疗患者。
FDA的药品评价和研究中心内血液学和肿瘤学产品室主任Richard Pazdur，M.D.说：“当2014年12月这个临床试验结果首次可得到时，FDA主动与公司工作有利于这个早期递交和审评，”“这个批准将为患者和卫生保健提供者提供伴随Opdivo生存获益的知识和将有助于指导患者医护和未来肺癌试验。”
在一项272例参加者，其中135例接受Opdivo和137例接受多西紫杉醇的随机化试验确定Opdivo治疗鳞状NSCLC的疗效。这个试验被设计测量开始治疗后参加者生存(总生存)的时间量。接受Opdivo参加者生存比接受多西紫杉醇[docetaxel]参加者平均较长3.2个月。
Opdivo治疗鳞状NSCLC的安全性和疗效被一项117例接受一个基于铂治疗和至少另外一种全身方案后进展的参加者单-臂试验支持。研究被设计测量客观反应率(ORR)，或经历肿瘤部分皱缩或完全消失参加者百分率。结果显示15%参加者经历ORR，其中59%有反应时间 6个月或更长。
Opdivo的最常见副作用是疲劳，气短，肌肉骨骼痛，食欲减退，咳嗽，恶心和便秘。最常见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，肾和激素-生成腺。
在FDA的优先审评程序下审评Opdivo对鳞状NSCLC，程序对治疗严重情况和，如被批准，某种严重情况的治疗中安全性或有效性提供显著改善的药物提供加快审评，Opdivo正在被批准比处方药用户收费目标日期2015年6月22日，即监管局计划完成申请审评日期提前大于三个月个月。
FDA以前批准Opdivo治疗患者对其他药物不再反应有不能用手术切除或转移黑色素瘤。
Opdivo由总部在新泽西Princeton 的Bristol-Myers Squibb公司上市。
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm436534.htm
IMPORTANT SAFETY INFORMATION ABOUT OPDIVO®(nivolumab)
OPDIVO® (nivolumab) is a medicine that may treat your melanoma by helping to work with your immune system. OPDIVO can cause your immune system to attack normal organs and tissues in many areas of your body and can affect the way they work. These problems can sometimes become serious or life-threatening and can lead to death. These problems may happen anytime during treatment or even after your treatment has ended.
Serious side effects may include:
•Lung problems (pneumonitis). Symptoms of pneumonitis may include: new or worsening cough; chest pain; and shortness of breath.
•Intestinal problems (colitis) that can lead to tears or holes in your intestine. Signs and symptoms of colitis may include: diarrhea (loose stools) or more bowel movements than usual; blood in your stools or dark, tarry, sticky stools; and severe stomach area (abdomen) pain or tenderness.
•Liver problems (hepatitis). Signs and symptoms of hepatitis may include: yellowing of your skin or the whites of your eyes; severe nausea or vomiting; pain on the right side of your stomach-area (abdomen); drowsiness; dark urine (tea colored); bleeding or bruise more easily than normal; and feeling less hungry than usual.
•Kidney problems, including nephritis and kidney failure. Signs of kidney problems may include: decrease in the amount of urine; blood in your urine; swelling in your ankles; and loss of appetite.
•Hormone gland problems (especially the thyroid, pituitary, and glands). Signs and symptoms that your hormone glands are not working properly may include: headaches that will not go away or unusual headaches; extreme tiredness, weight gain or weight loss; changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness; dizziness or fainting; hair loss; feeling cold; constipation; and voice gets deeper.
•Problems in other organs. Signs of these problems include: rash; changes in eyesight; severe or persistent muscle or joint pains; and severe muscle weakness.
Getting medical treatment right away may keep these problems from becoming more serious.
Your doctor will check you for these problems during treatment with OPDIVO. Your doctor may treat you with corticosteroid medicines and delay or completely stop treatment with OPDIVO, if you have severe side effects.
Pregnancy and Nursing:
Tell your healthcare provider if you are pregnant or plan to become pregnant. OPDIVO can harm your unborn baby. Females who are able to become pregnant should use an effective method of birth control during and for at least 5 months after the last dose of OPDIVO. Talk to your doctor about birth control methods that you can use during this time. Tell your doctor right away if you become pregnant during treatment with OPDIVO. Before receiving OPDIVO, tell your healthcare provider if you are breastfeeding or plan to breastfeed. It is not known if OPDIVO passes into your breast milk. Do not breastfeed during treatment with OPDIVO.
Tell your healthcare provider about:
•Your health problems or concerns if you: have immune system problems such as Crohn’s disease, ulcerative colitis, or lupus; have had an organ transplant; have lung, or breathing problems; have liver problems; or have any other medical conditions
•All the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements
The most common side effects of OPDIVO include: rash.
Tell your doctor if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of OPDIVO. For more information, ask your healthcare provider or pharmacist.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.
Please see U.S. FULL PRESCRIBING INFORMATION and MEDICATION GUIDE for OPDIVO® (nivolumab).
New Drugs Online Report for nivolumab
Information
Generic Name: nivolumab
Trade Name: Opdivo
Synonym: BMS-936558
Entry Type: Licence extension / variation
Development and Regulatory status
UK: Phase III Clinical Trials
EU: Phase III Clinical Trials
US: Phase III Clinical Trials
UK launch Plans: Available only to registered users
Actual UK launch date:
Comments
Jan 14: Nivolumab is the first PD-1 compound to receive Promising Innovative Medicine status from the MHRA for treatment of advanced skin cancer [10].
08/01/2015 11:44:12
Sep 14: Bristol-Myers and marketing partner Ono Pharmaceutical launch Opdivo in Japan for unresectable melanoma at an annual cost of $143,000 per patient. Analysts expect an annual cost of at least $110,000 in the US [8].
05/09/2014 10:47:33
Apr 13: The FDA has granted Fast Track designation for nivolumab in three tumour types: NSCLC, renal cell carcinoma and advanced melanoma [2].
26/04/2013 13:58:17
Trial or other data
Sep 14: BMS announce that interim analysis of a PIII trial showed nivolumab produced a 32% objective response rate among patients with advanced melanoma vs. 11% with chemotherapy control. The nivolumab arm also experienced a significantly lower rate of serious adverse events compared to the control - 9% to 31%. In addition, investigators reported that the median response rate had yet to be met in the nivolumab arm as responses were continuing [9].
30/09/2014 10:49:48
Jun 14: Bristol-Myers Squibb announce follow up results from Study -004, a multi-arm Phase 1b dose-ranging trial evaluating the safety and activity of the combination regimen of nivolumab and ipilimumab given either concurrently or sequentially in patients with advanced melanoma (n=127). After an additional year of follow up of the cohort that received the concurrent combination regimen of nivolumab 1 mg/kg plus ipilimumab 3mg/kg (n=17), the one-year overall survival (OS) rate was 94% and the two-year OS rate was 88%. These are the doses used in the ongoing Phase 2 and Phase 3 trials, CheckMate -069 and -067. No new safety signals were reported in the concurrent combination cohorts with additional follow up (n=53) and grade 3-4 treatment-related adverse events (AEs) occurred in 62% of patients. The most common were asymptomatic increases in lipase (15%), ALT (12%) and AST (11%) [6].
09/06/2014 12:30:43
Feb 14: PIII CheckMate-067 (NCT01844505) study is still recuiting pts. It is now expected to complete in Oct 17 [5].
24/03/2014 10:37:06
Jun 13: Results from a PI study ( NCT01024231) of concurrent therapy with nivolumab and ipilimumab in malignant melanoma published in N Engl J Med (June 2, 2013DOI: 10.1056/NEJMoa1302369). The combination had a manageable safety profile and provided clinical activity that appears to be distinct from that in published data on monotherapy, with rapid and deep tumour regression in a substantial proportion of patients.
03/06/2013 10:51:42
Evidence Based Evaluations
NHSC/NIHR http://www.hsc.nihr.ac.uk/topics/nivolumab-for-braf-v600-mutation-positive-advanced/
References
Available only to registered users
Category
BNF Category: Other immunomodulating drugs (08.02.04)
Pharmacology: Fully human Ig4 monoclonal antibody; programmed cell death-1 receptor (PDCD 1) inhibitor
Epidemiology: In 2008, the UK age-standardised incidence of melanoma for females was 16.5 (11.7 in 2001) and for males was 15.9 (10.1 in 2001) per 100,000 population. It has been estimated that the lifetime risk of developing malignant melanoma in 2008 was 1 in 61 for men and 1 in 60 for women in the UK [4]
Indication: Malignant melanoma
Additional Details: unresectable or metastatic BRAF-positive, first-line
Method(s) of Administration
Intravenous infusion
Company Information
Name: Bristol-Myers Squibb
US Name: Bristol-Myers Squibb
Further Information
Anticipated commissioning route (England) -
High cost drug list? Awaiting Update
Implications Available only to registered users
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