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辉瑞新一代ALK抑制剂Lorlatinib获FDA突破性疗法资格

2017年05月01日

编译：大叔

来源：大叔快评

2017年4月27日辉瑞宣布其在新一代ALK/ROS1抑制剂Lorlatinib获得FDA突破性疗法资格，针对ALK阳性转移性非小细胞肺癌既往接受过1或多个ALK抑制剂治疗患者。突破性疗法授权（Breakthrough Therapy Designation）是FDA为加速新药审评和批准设定的特殊机制，自2012实施以来，已经有多个肿瘤药物凭借此机制获得快速批准。

辉瑞负责肿瘤研发的首席研发官（Chief Development Office）Mace Rothenberg博士说“监管部门授予lorlatinib突破性疗法资格是对lorlatinib可能为ALK阳性患者提供重要治疗手段之潜力的认可，辉瑞快速研发lorlatinib体现了辉瑞对研发bio-marker驱动治疗以满足患者不断变化需求的承诺”。

基于正在进行的一项phase 1/2 研究的有效性和安全性数据，lorlatinib获得突破性疗法授权，lorlatinib的该项phase 1/2 纳入经过1种或多种ALK抑制剂治疗的ALK阳性转移性NSCLC患者。另外，一项名为CROWN的phase III 已经开始入组患者，CROWN研究为开放标签随机分组，比较lorlatinib 与crizoitinb 在晚期ALK阳性NSCLC中一线治疗的phase III研究。

【大叔解读】

辉瑞公司的第一款ALK抑制剂crizotinib 于2011年9月获得FDA批准，占据有利位置，奠定ALK阳性NSCLC翘楚地位。随后诺华的ceritinib（2014年4月）和罗氏的alectinib（2016年3月）分别获得ALK阳性晚期NSCLC二线适应症，进入ALK阳性只有5%的拥挤领域。2017年4月10日Roche 宣布Alex研究（alectinib 与crizotinib头对头一线比较）达到主要研究终点PFS，其详细数据可能在2017 ASCO公布。CROWN研究（lorlatinib vs crizotinb 头对头一线比较）的策略应该是用通过血脑屏障更佳的lorlatinib取代自己的crizotinb，避开与alectinib的正面交锋，继续占领ALK领导者地位。

Pfizer’s Next-Generation ALK/ROS1 Inhibitor, Lorlatinib, Granted Breakthrough Therapy Designation from FDA for ALK-Positive Metastatic Non-Small Cell Lung Cancer

NEW YORK--(BUSINESS WIRE)--Pfizer Inc. today announced that its investigational next-generation ALK/ROS1 tyrosine kinase inhibitor, lorlatinib, was granted Breakthrough Therapy designation from the U.S. Food and Drug Administration (FDA) for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC), previously treated with one or more ALK inhibitors.

Enacted as part of the 2012 FDA Safety and Innovation Act (FDASIA), Breakthrough Therapy designation is intended to expedite the development and review of a potential new medicine if it is intended to treat a serious or life-threatening disease and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies.1 The Breakthrough Therapy designation is distinct from the FDA’s other mechanisms to expedite drug development and review.2 ALK gene rearrangement is a genetic alteration that drives the development of lung cancer in some patients.3,4 Due to additional mutations that the tumor may acquire during treatment, disease progression remains a challenge in patients with ALK-positive metastatic NSCLC.5

“This regulatory designation recognizes the potential for lorlatinib to provide an important treatment option for patients with ALK-positive NSCLC whose cancers have progressed despite treatment. Pfizer’s rapid development of lorlatinib reflects a commitment to developing biomarker-driven therapies to meet the evolving needs of patients,” said Mace Rothenberg, MD, chief development officer, Oncology, Pfizer Global Product Development. “We look forward to working with the FDA to accelerate the development of this therapy.”

The Breakthrough Therapy designation is supported by the efficacy and safety data of an ongoing Phase 1/2 clinical trial of lorlatinib, which includes patients with ALK-positive NSCLC who were previously treated with one or more ALK inhibitors.

Additionally, the Phase 3 CROWN study (NCT03052608) recently began enrolling patients. CROWN is an ongoing, open label, randomized, two-arm study comparing lorlatinib to crizotinib in the first-line treatment of patients with metastatic ALK-positive NSCLC. Please visit clinicaltrials.gov for more information on this study.

参考文献

http://press.pfizer.com/press-release/pfizers-next-generation-alkros1-inhibitor-lorlatinib-granted-breakthrough-therapy-desi

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