Merck Receives Priority Review From FDA for New Drug Application for HIF-2α Inhibitor Belzutifan


2021-03-16 19:30:09 BioSpace


Application Based on Objective Response Rate From Phase 2 Trial Evaluating Belzutifan in Patients With Von Hippel-Lindau Disease-Associated Renal Cell Carcinoma New Filing Further Strengthens Merck’s Expanding and Diverse Oncology Portfolio KENILWORTH, N.J.--(BUSINESS WIRE)--Merck & Co. (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the U.S. Food and Drug Administration (FDA) has accepted and granted priority review for a New Drug Application (NDA) for the hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor belzutifan (pronounced bell-ZOO-ti-fan), a novel investigational candidate in Merck’s oncology pipeline, for the potential treatment of patients with von Hippel-Lindau (VHL) disease-associated renal cell carcinoma (RCC), not requiring immediate surgery. This NDA is based on data from the Phase 2 Study-004 trial, in which belzutifan showed a confirmed overall response rate of 36.1% (n=22/61) (95% CI: 24.2-49.4) in patients with VHL disease-associated RCC. The FDA has set a Prescription Drug User Fee Act (PDUFA), or target action, date of September 15, 2021. “Von Hippel-Lindau disease is a rare genetic condition for which there is no systemic treatment option available and is associated with a high risk of cancer development in multiple organs. In fact, up to 70% of patients with VHL develop renal cell carcinoma during their lifetime,” said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. “This priority review validates the important progress we have made to expand and diversify Merck’s oncology pipeline with innovative, new therapeutic approaches. We look forward to working closely with the FDA to bring belzutifan to patients in need.” Merck is also studying belzutifan in advanced RCC and other tumor types through a broad clinical program. In addition to the ongoing Phase 2 Study-004 trial, belzutifan is being evaluated in Phase 3 trials as monotherapy and as part of a combination regimen in previously treated patients and as part of a combination regimen as a first-line treatment for advanced clear cell RCC. About the Phase 2 Study-004 Trial This application is based on data from Study-004 (, NCT03401788), which is a Phase 2, open-label trial evaluating belzutifan for the potential treatment of patients with VHL disease who had at least one measurable solid tumor localized to the kidney and who did not require immediate surgery. The study enrolled 61 patients who received belzutifan 120 mg orally once daily until disease progression or unacceptable toxicity. The primary endpoint was objective response rate in VHL disease-associated RCC. Secondary endpoints in RCC tumors include disease control rate, duration of response, time to response, progression-free survival, time to surgery and safety. Additionally, this study evaluated response rates in other common VHL disease-associated tumors, including pancreatic cysts, pancreatic neuroendocrine tumors, central nervous system (CNS) hemangioblastomas, and retinal hemangioblastomas. About Belzutifan Belzutifan (MK-6482) is a novel, potent and selective inhibitor of HIF-2α. Proteins known as hypoxia-inducible factors, including HIF-2α, can accumulate in patients when VHL, a tumor-suppressor protein, is inactivated. If not properly regulated, the accumulation of HIF-2α can stimulate several oncogenes associated with cellular proliferation, angiogenesis and tumor growth, leading to the growth of both benign and malignant tumors. This inactivation of VHL has been observed in more than 90% of clear cell RCC tumors. Research into VHL biology that led to the discovery of HIF-2α was awarded the Nobel Prize in Physiology or Medicine in 2019. About Von Hippel-Lindau Disease and Renal Cell Carcinoma Von Hippel-Lindau disease is a rare genetic disease that affects one in 36,000 people (200,000 cases worldwide and 10,000 cases in the U.S. alone). Patients with VHL disease are at risk for benign blood vessel tumors as well as several cancers, including RCC. As many as 70% of people with VHL disease develop RCC. Renal cell carcinoma is by far the most common type of kidney cancer; about nine of 10 kidney cancers are RCCs, and about seven of 10 RCCs are clear cell. Worldwide, it is estimated there were nearly 431,300 cases of kidney cancer diagnosed and almost 179,400 deaths from the disease in 2020. In the U.S. alone, it is estimated there will be almost 76,100 new cases of kidney cancer diagnosed and nearly 13,800 deaths from the disease in 2021. Merck’s Focus on Cancer Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit About Merck For 130 years, Merck, known as MSD outside of the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world’s most challenging diseases in pursuit of our mission to save and improve lives. We demonstrate our commitment to patients and population health by increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to prevent and treat diseases that threaten people and animals – including cancer, infectious diseases such as HIV and Ebola, and emerging animal diseases – as we aspire to be the premier research-intensive biopharmaceutical company in the world. For more information, visit and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn. Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., USA This news release of Merck & Co., Inc., Kenilworth, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of the global outbreak of novel coronavirus disease (COVID-19); the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions. The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s 2020 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site ( View source version on Media Contacts: Patrick Ryan (973) 275-7075 Rebecca Newberry (484) 678-2952 Investor Contacts: Peter Dannenbaum (908) 740-1037 Courtney Ronaldo (908) 740-6132 Source: Merck & Co., Inc. View this news release online at:
贝珠替芬治疗Von Hippel-Lindau病相关肾癌2期临床疗效评价 新的申请进一步加强了默克不断扩大和多样化的肿瘤产品组合 新泽西州KENILWORTH(商业电讯)--默克公司(纽约证券交易所代码:MRK)(在美国和加拿大以外被称为MSD)今天宣布,美国食品和药物管理局(FDA)已经接受并批准了一项新的药物申请(NDA)的优先审查,该申请涉及缺氧诱导因子-2 alpha(HIF-2a)抑制剂belzutifan(发音为bell-ZOO-ti-fan)。这是默克公司肿瘤学管道中的一种新的研究候选药物,用于治疗冯·希佩尔-林道(VHL)疾病相关肾细胞癌(RCC)患者,不需要立即手术。该NDA基于2期Study-004试验的数据,在该试验中,belzutifan显示VHL疾病相关RCC患者的确认总应答率为36.1%(n=22/61)(95%CI:24.2-49.4)。FDA已经制定了一个处方药使用费法案(PDUFA),或目标行动,日期为2021年9月15日。 “von Hippel-Lindau病是一种罕见的遗传性疾病,没有全身治疗的选择,并且与多器官癌症发展的高风险相关。事实上,高达70%的VHL患者在一生中发展为肾细胞癌,“默克研究实验室临床研究副总裁Scot Ebbinghaus博士说。“这一优先审查证实了我们在通过创新的、新的治疗方法扩大和多样化默克肿瘤学管道方面所取得的重要进展。我们期待着与FDA密切合作,将belzutifan带给有需要的患者。“ 默克公司也在通过一个广泛的临床项目,在晚期RCC和其他肿瘤类型中研究贝祖替芬。除了正在进行的2期研究-004试验外,贝尔祖替芬还在3期试验中作为单一疗法和作为联合方案的一部分在先前治疗的患者中进行评估,并作为联合方案的一部分作为晚期透明细胞RCC的一线治疗。 关于第2期研究-004试验 本申请基于来自Study-004(,NCT03401788)的数据,这是一个2期开放标记试验,评估贝珠替芬对VHL病患者的潜在治疗,这些患者至少有一个可测量的位于肾脏的实体瘤,并且不需要立即手术。该研究纳入了61名患者,他们每日一次口服贝珠替芬120毫克,直到疾病进展或不可接受的毒性。主要终点是VHL疾病相关肾癌的客观反应率。RCC肿瘤的次要终点包括疾病控制率、反应持续时间、反应时间、无进展生存期、手术时间和安全性。 此外,本研究评估了其他常见VHL疾病相关肿瘤的应答率,包括胰腺囊肿、胰腺神经内分泌肿瘤、中枢神经系统(CNS)血管母细胞瘤和视网膜血管母细胞瘤。 关于Belzutifan Belzutifan(MK-6482)是一种新型、高效、选择性的HIF-2抑制剂。当肿瘤抑制蛋白VHL失活时,包括HIF-2a在内的称为低氧诱导因子的蛋白质可在患者体内积累。如果不适当调控,HIF-2a的积累会刺激与细胞增殖、血管生成和肿瘤生长相关的几个癌基因,从而导致良、恶性肿瘤的生长。在90%以上的透明细胞RCC肿瘤中观察到VHL的这种失活。对VHL生物学的研究导致了HIF-2a的发现,因此获得了2019年诺贝尔生理学或医学奖。 关于Von Hippel-Lindau病与肾癌 Von Hippel-Lindau病是一种罕见的遗传病,36000人中就有一人发病(全球20万例,仅美国就有1万例)。VHL病患者有患良性血管肿瘤以及包括肾细胞癌在内的几种癌症的风险。多达70%的VHL患者发展为肾癌。 肾细胞癌是迄今为止最常见的肾癌类型;10例肾癌中约有9例为肾细胞癌,10例肾细胞癌中约有7例为透明细胞癌。据估计,2020年全世界有近431300例肾癌确诊病例,近179400人死于该疾病。据估计,仅在美国,到2021年将有近76,100例肾癌新确诊病例,近13,800人死于这种疾病。 默克公司对癌症的关注 我们的目标是将突破性的科学转化为创新的肿瘤药物,以帮助全世界的癌症患者。在默克公司,为癌症患者带来新希望的潜力驱动着我们的目标,支持癌症药物的可及性是我们的承诺。作为我们专注于癌症的一部分,默克致力于探索免疫肿瘤学的潜力,拥有业界最大的跨越30多种肿瘤类型的开发项目之一。我们还继续通过战略收购来加强我们的投资组合,并优先发展几个有潜力改善晚期癌症治疗的有前途的肿瘤学候选者。有关肿瘤临床试验的更多信息,请访问。 关于默克 130年来,默克公司,在美国和加拿大以外被称为MSD,一直在为生命发明,为世界上许多最具挑战性的疾病提供药物和疫苗,以追求我们拯救和改善生命的使命。我们通过影响深远的政策、方案和伙伴关系,增加获得保健的机会,以此表明我们对患者和人口健康的承诺。今天,默克继续站在预防和治疗威胁人类和动物的疾病的研究前沿--包括癌症、HIV和埃博拉等传染病,以及新出现的动物疾病--因为我们立志成为世界上首屈一指的研究密集型生物制药公司。欲了解更多信息,请访问,并在Twitter、Facebook、Instagram、YouTube和LinkedIn上与我们联系。 美国新泽西州凯尼尔沃思默克公司的前瞻性声明 Merck&Co.,Inc.,Kenilworth,N.J.,USA(“公司”)的本新闻稿包括1995年《美国私人证券诉讼改革法案》安全港条款含义范围内的“前瞻性陈述”。这些陈述是基于本公司管理层目前的信念和预期,并受到重大风险和不确定性的影响。对于管道产品,不能保证产品将获得必要的监管批准,也不能保证产品将证明在商业上是成功的。如果基本假设被证明不准确或风险或不确定性成为现实,实际结果可能与前瞻性陈述中提出的结果大不相同。 风险和不确定性包括但不限于,一般行业状况和竞争情况;一般经济因素,包括利率和货币汇率波动;新型冠状病毒病(COVID-19)全球暴发的影响;美国及国际医药行业监管与医疗立法的影响;控制保健费用的全球趋势;竞争对手取得的技术进步、新产品和专利;新产品开发固有的挑战,包括获得监管批准;公司准确预测未来市场行情的能力;制造困难或延误;国际经济金融不稳定性与主权风险;对创新产品的公司专利和其他保护有效性的依赖;和/或监管行动。 公司不承担公开更新任何前瞻性陈述的义务,无论是由于新信息、未来事件或其他原因。可能导致结果与前瞻性陈述中描述的结果有重大差异的其他因素可以在公司的2020年年度报告10-K表格中找到,以及公司向证券交易委员会(SEC)提交的其他文件,这些文件可在SEC的互联网站点(上查阅。 在BusinessWire.com上查看源版本: 媒体联系人: 帕特里克·赖安 (973)275-7075 丽贝卡·纽贝里 (484)678-2952 投资者联系人: 彼得·丹南鲍姆 (908)740-1037 库特尼·罗纳尔多 (908)740-6132 资料来源:默克公司。 请在以下网址联机查看此新闻稿: