2018年6月28日，Array BioPharma是一家专注于发现、开发和商业化小分子药物治疗癌症的美国生物制药公司。近日，该公司宣布，美国食品和药物管理局（FDA）已批准Braftovi（binimetinib，一种MEK抑制剂）胶囊联合Mektovi（encorafenib，一种BRAF抑制剂）片剂，用于经FDA批准的一种检测方法证实存在BRAF V600E或BRAF V600K突变的不可切除性或转移性黑色素瘤患者的治疗。值得注意的是，Braftovi不适用于野生型BRAF黑色素瘤的治疗。

此次批准也是Braftovi+Mektovi组合方案的首个监管批准，该方案上市后，将在晚期BRAF突变黑色素瘤细分市场，主要针对诺华公司的Tafinlar+Mekinist方案展开竞争。华尔街知名投行Jefferies认为，在这一细分市场，Braftovi+Mektovi组合方案可以比诺华的组合方案做的更好，后者在该市场的年销售额额大约为4亿美元。

MEK和BRAF是MAPK信号通路（RAS-RAF-MEK-ERK）中的关键蛋白激酶。研究表明，这一通路调节了包括细胞增殖、分化、存活、血管生成在内的多种关键细胞活动。在许多癌症中，如黑色素瘤、结直肠癌和甲状腺癌，这一信号通路中的蛋白质已被证实异常激活。

binimetinib是一种MEK抑制剂，encorafenib则是一种BRAF抑制剂，这2种药物均靶向该信号通路中的关键酶。目前，Array也正在评估binimetinib和encorafenib治疗其他类型癌症的潜力，包括BRAF突变结直肠癌。

Braftovi+Mektovi组合方案的获批，是基于III期临床研究COLUMBUS的结果。数据显示，与罗氏黑的晚期色素瘤特效药Zelboraf（vemurafenib，威罗菲尼）相比，Braftovi+Mektovi组合方案无进展生存期延长了一倍（中位PFS：14.9个月 vs 7.3个月，HR=0.54，95%CI:0.41-0.71，p＜0.0001）。该研究中，Braftovi+Mektovi方案组仅有5%的患者因不良反应停止治疗，该方案组最常见的不良反应（≥25%）为疲劳、恶心、腹泻、呕吐、腹痛和关节痛。

今年2月公布的COLUMBUS研究总生存期（OS）分析数据显示，与Zelboraf（960mg，每日一次）相比，Braftovi+Mektovi方案显著降低了死亡风险（HR=0.61，95%CI:0.47-0.79，p＜0.0001）：Zelboraf单药组中位OS为16.9个月，Braftovi+Mektovi方案组中位OS为33.6个月。这些积极数据进一步增强了BRAF/MEK抑制剂组合疗法的临床证据。

黑色素瘤基金会主席Valerie Guild评论称，Braftovi+Mektovi方案是治疗BRAF突变黑色素瘤在III期临床中生存期超过30个月的首个靶向疗法，代表着BRAF突变黑色素瘤的一种新的临床护理保准。鉴于有近一半的确诊为转移性黑色素瘤的患者检测到了BRAF突变，Braftovi+Mektovi方案的获批，对黑色素瘤患者群体而言将是一个莫大的好消息，将满足该类患者群体中存在的一个关键未满足医疗需求

Array BioPharma Announces FDA Approval of BRAFTOVI™ (encorafenib) in Combination with MEKTOVI® (binimetinib) 

– Approval based on Phase 3 COLUMBUS trial which demonstrated nearly 15 months median progression-free survival –

– BRAFTOVI + MEKTOVI now available for patients with advanced BRAF-mutant melanoma –

Boulder, Colo. (June 27, 2018) – Array BioPharma Inc. (Nasdaq: ARRY) today announced that the U.S. Food and Drug Administration (FDA) has approved BRAFTOVI™ capsules in combination with MEKTOVI® tablets for the treatment of patients with unresectable or metastatic melanoma with a BRAFV600E or BRAFV600K mutation, as detected by an FDA-approved test. BRAFTOVI is not indicated for the treatment of patients with wild-type BRAF melanoma. 

“We are thrilled with the approval of BRAFTOVI + MEKTOVI, which help fill a critical unmet need for patients with advanced BRAF-mutant melanoma, a serious and deadly type of skin cancer,” said Ron Squarer, Chief Executive Officer, Array BioPharma. “As presented at ASCO, BRAFTOVI + MEKTOVI is the first targeted treatment to demonstrate over 30 months median overall survival in a Phase 3 trial. These products represent a new standard of care for BRAF-mutant melanoma patients and we sincerely thank the patients and dedicated researchers who participated in our clinical program.” 

BRAFTOVI + MEKTOVI are now available to order through select specialty pharmacies in the U.S. market. 

“Despite recent advances, there remains a significant unmet need for treatments that are both effective and well-tolerated for patients with BRAF-mutant melanoma,” said Keith T. Flaherty, M.D., Director of the Termeer Center for Targeted Therapy, Massachusetts General Hospital Cancer Center and Profess