Binimetinib

▎药明康德内容团队报道 今日（2月27日），中国国家药监局药品审评中心（CDE）官网公示，皮尔法伯（Pierre Fabre）申报的恩考芬尼胶囊和比美替尼片的上市申请获得受理。 公开资料显示，恩考芬尼（encorafenib，Braftovi）是一种口服小分子BRAF激酶抑制剂，比美替尼（binimetinib，Mektovi）是一种强效且具有选择性的MEK抑制剂。二者组合疗法此前已经获美国FDA和欧盟委员会批准，用于治疗带有BRAF V600突变的不可切除或转移性黑色素瘤患者；以及治疗BRAF V600E突变的转移性非小细胞肺癌（NSCLC）患者。本次是这款组合疗法首次在中国申报上市。 截图来源：CDE官网 恩考芬尼是一种强效且具有高度选择性的BRAF抑制剂，通过抑制肿瘤细胞中表达多种突变形式的BRAF激酶（包括V600E）的RAF/MEK/ERK通路发挥作用；比美替尼是一种强效且具有选择性的MEK抑制剂。这两种药物通过抑制MAPK通路中的激酶来发挥作用，从而产生具有临床相关性的抗肿瘤活性。MAPK通路在BRAFV600E突变的非小细胞肺癌中会被持续性地激活。已有研究证明，许多癌症都出现了该通路激活不受控制的现象，包括黑色素瘤、结直肠癌（CRC）和NSCLC。 根据皮尔法伯公开资料介绍，辉瑞（Pfizer）拥有Braftovi和Mektovi在美国、加拿大以及拉丁美洲、非洲和中东地区所有国家的独家商业权利。小野制药拥有这两种产品在日本和韩国的独家商业权，Medison拥有以色列的独家商业权，皮尔法伯拥有这两种产品在所有其他国家（包括欧洲和亚太地区）的独家商业权。 截图来源：中国药物临床试验登记与信息公示平台 根据中国药物临床试验登记与信息公示平台，皮尔法伯正在中国开展一项国内2期临床研究，旨在BRAF抑制剂和MEK抑制剂初治的中国BRAF V600E突变转移性非小细胞性肺癌患者中评估恩考芬尼联合比美替尼的疗效、安全性和药代动力学。该研究目前已经招募完成。根据该研究进展可以推测，本次这款联合疗法在中国申报上市的适应症可能是BRAF V600E突变的非小细胞肺癌。 针对该项适应症，欧盟委员会（EC）已于2024年9月批准恩考芬尼联合比美替尼联合疗法。此次批准基于2期PHAROS试验的结果，这是一项全球性、开放标签、多中心、非随机试验，旨在确定恩考芬尼联合比美替尼对未接受过治疗和之前接受过治疗的BRAF V600E突变转移NSCLC患者的疗效和安全性。结果显示，在未接受过治疗的患者群体（59人）中，客观缓解率（ORR）为75%，其中包括15%的完全缓解（CR）和59%的部分缓解（PR）。更新结果显示，在额外10个月的随访后，64%的患者在至少12个月内维持了缓解，持续时间中位数（mDOR）为40个月。对于曾接受过先前治疗的患者（39人），IRR确定的ORR为46%，包括10%的CR和36%的PR。更新结果显示，在额外10个月的随访后，44%的患者在至少12个月内维持了缓解，mDOR为16.7个月。 除了BRAF V600E突变的非小细胞肺癌适应症，恩考芬尼还有多项适应症已经获得FDA和欧盟委员会批准，包括恩考芬尼联合比美替尼用于治疗具有BRAFV600突变的不可切除或转移性黑色素瘤成年患者，与西妥昔单抗联合用于治疗携带BRAFV600E突变的转移性结直肠癌成年患者。在中国，恩考芬尼的首个上市申请已经于2024年9月获得CDE受理。 期待这款新药后续临床研究顺利进行，早日为更多患者带来新的治疗选择。 参考资料： [1]中国国家药监局药品审评中心官网. Retrieved Feb 27， 2025, from https://www.cde.org.cn/main/xxgk/listpage/4b5255eb0a84820cef4ca3e8b6bbe20c [2]皮尔法伯BRAFTOVI与MEKTOVI联合疗法获欧盟委员会批准，用于治疗携带BRAF V600E 突变的aNSCLC成年患者. Retrieved Sep 23， 2024, from  https://mp.weixin.qq.com/s/dunO_eXXCtdeSx3cxpftcQ 本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权及其他合作需求，请联系wuxi_media@wuxiapptec.com。 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。

Dive Brief:Adding Pfizers cancer drug Braftovi to standard treatments helped people with a form of colorectal cancer live longer without their disease worsening than those who got the typical care alone in a Phase 3 trial, the company said Monday.The result confirms earlier research from the study, called Breakwater, which had shown that trial volunteers receiving Braftovi were significantly more likely to see their tumors shrink or disappear. Those data were used to support an accelerated U.S. clearance for Braftovi in colorectal cancer in December.Pfizer has been under pressure from investors to grow revenue amid plummeting sales for its COVID-19 treatments, and cancer drug research is one area it hopes can pick up the slack. Braftovi and the related drug Mektovi, which Pfizer acquired in a 2019 deal for Array BioPharma, generated $437 million in sales through the first nine months of 2024.Pfizer reports full-year earnings on Tuesday.Dive Insight:Braftovi is a targeted medicine aimed at a particular mutation, V600E, to the BRAF gene.BRAF mutations occur in about 10% of people with colorectal cancer, and the V600E is the most common among them.A regimen of Braftovi and Mektovi is already approved in skin and lung cancers. In colorectal tumors, the drug is used in advanced disease with a drug called cetuximab. Those two are prescribed alongside chemotherapy in the frontline setting under the speedy clearance issued in December.Pfizer acquired Braftovi and Mektovi in an $11.4 billion buyout of Array BioPharma in 2019. At the time, the two drugs were only cleared for melanoma. Pfizer broadened use to other tumors afterward, but they still only generate modest revenue compared to other cancer drugs in the companys portfolio. The new results revealed on Monday could boost those numbers, though, as Pfizer claimed, without revealing specific details, that Braftovi helped delay tumor progression and extend the lives of colorectal cancer patients.Since the Array deal, Pfizer has shifted away from targeted small-molecule drugs for cancer and towards biologics. Antibody-drug conjugates, such as those acquired in a $43 billion deal for Seagen, are a focus and part of a plan to have biologics account for 65% of its oncology revenue by 2030 compared to only 6% in 2023.Patents for two of Pfizers biggest sellers in cancer, Xtandi and Ibrance, expire in 2027. '