2011年3月25日,美国食品与药物管理局(FDA)发布公告,批准Yervoy(活性成分:ipilimumab)用于治疗晚期(转移性)黑色素瘤。 黑色素瘤是最危险的皮肤癌类型。经Yervoy治疗后,黑色素瘤患者生存时间将延长。 由于存在与Yervoy相关的罕见和严重的副作用,该疗法被“风险评估和减低策略”(Risk Evaluation and Mitigation Strategy)批准,以告知医疗专业人员这些严重的风险。药物治疗指南也将同时提供给患者,以告知他们治疗的潜在副作用。 “晚期黑色素瘤是毁灭性的,只有极少的治疗方案可提供给患者,而且以前,这些方案中没有一个能延长患者的生命”,FDA药物评价和研究中心肿瘤药品办公室主任Pazdur博士说。“Yervoy是第一个被FDA批准、并能清楚显示转移性黑色素瘤患者用药后可延长生存时间的治疗方法。” 黑色素瘤是皮肤疾病导致死亡的首要原因。根据美国国家癌症研究所的数据,2010年,在美国,估计有68130例新诊断的黑色素瘤病例,约8700人死于这种疾病。 相关链接:FDA approves new treatment for a type of late-stage skin cancer PRINCETON, N.J.-Bristol-Myers Squibb Company (NYSE: BMY) today announced that the U.S. Food and Drug Administration (FDA) approved YERVOY™ (ipilimumab) 3 mg/kg for the treatment of patients with unresectable (inoperable) or metastatic melanoma. YERVOY is the first and only therapy for unresectable or metastatic melanoma to demonstrate a significant improvement in overall survival based on results from a pivotal randomized, double-blind Phase 3 study. Median overall survival was 10 months (95% CI: 8.0-13.8) for YERVOY, 6 months (95% CI: 5.5-8.7) for gp100 and 10 months (95% CI: 8.5-11.5) for YERVOY + gp100, with p-values of 0.0026 (not adjusted for multiple comparisons) for YERVOY and 0.0004 for YERVOY + gp100 vs. gp100, respectively. As published in the New England Journal of Medicine, the Kaplan-Meier estimated survival rate at 1 year was 46% (95% CI: 37.0, 54.1) in the YERVOY arm vs. 25% (95% CI: 18.1, 32.9) in the gp100 arm. The estimated survival rate at 2 years was 24% (95% CI: 16.0, 31.5) in the YERVOY arm vs. 14%2 (95% CI: 8.0, 20.0) in the gp100 arm. YERVOY, which is a recombinant, human monoclonal antibody, is the first FDA-approved cancer immunotherapy that blocks the cytotoxic T- lymphocyte antigen-4 (CTLA-4). “Metastatic melanoma is one of the most aggressive forms of cancer and despite the rising incidence, no new treatments have been approved in more than a decade” The full Prescribing Information for YERVOY includes a boxed warning for immune-mediated adverse reactions. YERVOY can result in severe and fatal immune-mediated adverse reactions due to T-cell activation and proliferation. These immune-mediated reactions may involve any organ system; however, the most common severe immune-mediated adverse reactions are enterocolitis, hepatitis, dermatitis (including toxic epidermal necrolysis), neuropathy, and endocrinopathy. The majority of these immune-mediated reactions initially manifested during treatment; however, a minority occurred weeks to months after discontinuation of YERVOY (ipilimumab). Permanently discontinue YERVOY and initiate systemic high-dose corticosteroid therapy for severe immune-mediated reactions. Patients should be assessed for signs and symptoms of enterocolitis, dermatitis, neuropathy and endocrinopathy and clinical chemistries should be evaluated, including liver function tests and thyroid function tests, at baseline and before each dose. Please see complete Important Safety Information including Boxed WARNING regarding immune-mediated adverse reactions on pages 6-9. “Metastatic melanoma is one of the most aggressive forms of cancer and despite the rising incidence, no new treatments have been approved in more than a decade,” said Lamberto Andreotti, chief executive officer, Bristol-Myers Squibb. “Today’s approval of YERVOY is an example of Bristol-Myers Squibb living its mission of developing and delivering innovative medicines that address the unmet needs of patients with serious diseases. It also represents a significant step forward in our commitment to deliver and execute against our differentiated and focused BioPharma strategy.” “For the first time, oncologists have a treatment option for patients with unresectable or metastatic melanoma that has been proven in a randomized Phase 3 clinical trial to significantly extend the lives of patients,” said Steven J. O’Day, M.D., Chief of Research and Director of the Melanoma Program at The Angeles Clinic and Research Institute, California, and an investigator of the pivotal trial. “In fact, the Kaplan-Meier curve from this study suggests a prolonged survival benefit for some patients.” Median overall survival was 10 months (95% CI: 8.0-13.8) for YERVOY (ipilimumab), 6 months (95% CI: 5.5-8.7) for gp100 and 10 months (95% CI: 8.5-11.5) for YERVOY + gp100, with p-values of 0.0026 (not adjusted for multiple comparisons) for YERVOY and 0.0004 for YERVOY + gp100 vs gp100, respectively. “The FDA approval of YERVOY is the culmination of more than 14 years of research and development by our dedicated development teams and clinical trial investigators,” said Elliott Sigal, M.D., Ph.D., executive vice president, chief scientific officer, and president, Research & Development, Bristol-Myers Squibb. “YERVOY is the first FDA-approved compound from our robust immuno-oncology pipeline, which comprises a variety of other compounds with the potential to harness the patient’s immune system to fight cancer.” The mechanism of action of ipilimumab’s effect in patients with melanoma is indirect, possibly through T-cell mediated anti-tumor immune responses. Bristol-Myers Squibb has agreed with the FDA to conduct a post-marketing study comparing the safety and efficacy of the 3 mg/kg dose vs. an investigational 10 mg/kg dose in patients with unresectable or metastatic melanoma. The company expects to begin shipping YERVOY within weeks of today’s FDA approval. YERVOY is the first and only therapy to demonstrate a statistically significant overall survival benefit in patients with unresectable or metastatic melanoma. The approval is based on a Phase 3, randomized (3:1:1), double-blind study that included 676 patients with unresectable or metastatic melanoma who were previously treated with one or more of the following: aldesleukin, dacarbazine, temozolomide, fotemustine, or carboplatin. As published in the New England Journal of Medicine, the Kaplan-Meier estimated survival rate at 1 year was 46% (95% CI: 37.0, 54.1) in the YERVOY arm vs. 25% (95% CI: 18.1, 32.9) in the gp100 arm. The estimated survival rate at 2 years was 24% (95% CI: 16.0, 31.5) in the YERVOY arm vs. 14%2 (95% CI: 8.0, 20.0) in the gp100 arm. Patients treated with YERVOY had a 34% reduction in the risk of death over the gp100 control arm (HR = 0.66 [95% CI: 0.51-0.87], P=0.0026). Patients treated with YERVOY (ipilimumab) plus gp100 had a 32% reduction in the risk of death over the gp100 control arm (HR = 0.68 [95% CI: 0.55-0.85], P=0.0004). Median overall survival was 10 (95% CI: 8.0-13.8), 10 (95% CI: 8.5-11.5) and 6 (95% CI: 5.5-8.7) months for the YERVOY alone, YERVOY + gp100 arm and gp100 alone arms, respectively. The best overall response rate (BORR) as assessed by the investigator was 10.9% (95% CI: 6.3, 17.4) in patients treated with YERVOY (ipilimumab) (n=15 of 137), 5.7% (95% CI: 3.7, 8.4) in the YERVOY + gp100 arm (n=23 of 403) and 1.5% (95% CI: 0.2, 5.2) in the gp100 arm (n=2 of 136). BORR is defined as the total number of patients with the best response of a complete response (CR) or a partial response (PR) divided by the total number of patients treated. The median duration of response was 11.5 months in the YERVOY + gp100 arm and has not been reached in the YERVOY or gp100 arm at the time of the analysis because more than half of patients who had a confirmed CR or PR remained free of any relapse. In patients who received 3 mg/kg YERVOY alone (n=131), severe to fatal immune-mediated adverse reactions were reported and included enterocolitis (7%), endocrinopathy (4%, all of which had hypopituitarism), dermatitis (2%), hepatitis (1%), neuropathy (1%), nephritis (1%), and eosinophilia (1%). In patients who received 3 mg/kg of YERVOY + gp100 (n=380) severe to fatal immune-mediated adverse reactions were reported and included enterocolitis (7%), hepototoxicity (2%), dermatitis (3%), endocrinopathy (1%, hypopituitarism, 1% adrenal insufficiency), pneumonitis (<1%), meningitis (<1%), pericarditis (<1%).The most common adverse reactions were fatigue (41%), diarrhea (32%), pruritus (31%), rash (29%) and colitis (8%) for the YERVOY alone arm, diarrhea (37%), fatigue (34%), rash (25%), pruritus (21%), and colitis (5%) for the YERVOY +gp100 arm, and fatigue (31%), diarrhea (20%), pruritus (11%), rash (8%), and colitis (2%) for gp100 arm. YERVOY therapy was discontinued for adverse reactions in 10% of patients. Please see complete Important Safety Information including Boxed WARNING regarding immune-mediated adverse reactions on pages 6-9. YERVOY: Risk Evaluation and Mitigation Strategy The YERVOY Risk Evaluation and Mitigation Strategy (REMS) consists of a Communication Plan to inform potential prescribers and supportive healthcare providers about serious adverse reactions associated with YERVOY. To support this communication plan, Bristol-Myers Squibb has put in place a system that will enable the company to deliver these educational materials to the appropriate healthcare professional at the time of product order. The approval is based on a Phase 3, double-blind study that randomized 676 patients with unresectable or metastatic melanoma who were previously treated with one or more of the following: aldesleukin, dacarbazine, temozolomide, fotemustine, or carboplatin. Patients were randomized in a 3:1:1 ratio to receive either YERVOY (ipilimumab) (3mg/kg) in combination with the investigational peptide vaccine gp100 (n=403), YERVOY alone (3mg/kg; n=137), or gp100 alone (n=136). The primary endpoint of the pivotal Phase 3 study was overall survival in the YERVOY plus gp100 arm vs. the gp100 arm. Secondary efficacy endpoints included overall survival in the YERVOY plus gp100 arm vs. the YERVOY arm, overall survival in the YERVOY arm vs. the gp100 arm, BORR at week 24 and duration of response. Patients received YERVOY (3mg/kg) as an intravenous infusion administered over 90 minutes every 3 weeks for four doses. Assessment of tumor response to YERVOY was conducted at weeks 12 and 24, and every 3 months thereafter. Patients with evidence of objective tumor response at 12 or 24 weeks had assessment for confirmation of durability of response at 16 or 28 weeks, respectively. Between 57% and 64% of patients treated in each study arm received all four planned doses. YERVOY was studied in patients with a typically poor prognosis, including those with brain metastases, elevated LDH, and visceral disease (M1c). In the study, 71% had M1c stage, 12% had a history of previously-treated brain metastasis, 98% had ECOG performance status of 0 and 1, 23% had received aldeskeukin and 38% had elevated LDH level. Additionally, 29% of patients were 65 years or older with a median age of 57 years. The median duration of follow-up was 8.9 months. Please see complete Important Safety Information including Boxed WARNING regarding immune-mediated adverse reactions on pages 6-9. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a negative regulator of T-cell activation. Ipilimumab binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA-4 has been shown to augment T-cell activation and proliferation. The mechanism of action of ipilimumab’s effect in patients with melanoma is indirect, possibly through T-cell mediated anti-tumor immune responses. YERVOY (ipilimumab) was granted orphan drug status in 2004, which is a designation given to drugs that treat rare diseases. In 2006, YERVOY received a fast track designation. The FDA’s fast track process is designed to facilitate the development, and expedite the review, of drugs to treat serious diseases and fill an unmet medical need. The purpose is to get important new drugs to the patient earlier. In August of 2010, YERVOY received a priority review designation, which is given to drugs that offer major advances in treatment, or provide a treatment where no adequate therapy exists. Metastatic Melanoma is the Deadliest Form of Skin Cancer “Metastatic melanoma is a devastating disease and treating it has been a significant challenge,” said Tim Turnham, executive director of the Melanoma Research Foundation. “The incidence of melanoma has been increasing for at least 30 years. The median age at diagnosis for melanoma is 57 and the median age at death is 67.” About Bristol-Myers Squibb’s Patient Access Programs In addition to Destination Access, Bristol-Myers Squibb has developed the YERVOY Co-Pay Program to help eligible, commercially insured patients who have been prescribed YERVOY for unresectable or metastatic melanoma with their co-pay or co-insurance costs for this drug. Additional information about this program will be available at www.YERVOY.com. Important Safety Information Assess patients for signs and symptoms of enterocolitis, dermatitis, neuropathy and endocrinopathy and evaluate clinical chemistries including liver function tests (LFTs) and thyroid function tests at baseline and before each dose. Withhold dose for moderate immune-mediated adverse reactions until return to baseline, improvement to mild severity, or complete resolution, and patient is receiving <7.5 mg prednisone or equivalent per day. Permanently discontinue YERVOY for any of the following: Immune-mediated Enterocolitis: Immune-mediated Dermatitis: Immune-mediated Neuropathies: Immune-Mediated Endocrinopathies: Other Immune-mediated Adverse Reactions, Including Ocular Manifestations: Common Adverse Reactions: |