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康方生物又赢了一次。4月23日,康方生物发布公告,PD-1/VEGF双抗药物依沃西单抗,在一线治疗晚期鳞状非小细胞肺癌(sq-NSCLC)的III期注册临床研究中,以"决定性胜出"的阳性结果,击败替雷利珠单抗联合化疗。

这是依沃西单抗第二个头对头获胜,2024年,依沃西单抗头对头战胜全球"药王"K药。但这一次康方生物选择了国产PD-1替雷利珠单抗做对手,这是为什么?

有业内人士告诉健识局:“百济神州在晚期鳞癌这个适应症上临床试验做得比较扎实,用替雷利珠单抗来进行对照,谁也不会说康方挑了个软柿子来捏。”替雷利珠单抗2024年销售额超44亿元,是国产PD-1的“销冠”。此次,康方生物选择的也算是国内的"最强对手"。

在这一消息公布后,康方生物股价连涨两日,市值增长超百亿港元。资本市场用真金白银,为这次头对头试验投下支持票。

为什么是替雷利珠单抗?

在免疫治疗时代之前,双药化疗是晚期鳞状NSCLC的一线标准治疗,但临床获益有限,患者的中位总生存期(OS)通常不超过12个月。直到2018年,K药成为首个联合化疗获批一线治疗晚期鳞状NSCLC的PD-1,这部分患者也获得了新希望,OS和无进展生存期(PFS)都得到了极大改善,

既然K药这么强,康方生物为什么不找K药做头对头?

上述人士告诉健识局:一方面,康方的合作伙伴summit已经在国外做了K药+化疗对照组;另一方面,做头对头要买药,K药的价格太高,试验成本太大。

健识局查询Clinictrial网站得知,Summit公司正在参与HARMONi-3的临床试验,比较依沃西单抗联合化疗与K药联合化疗在一线转移性鳞状非小细胞癌中的疗效,开展美国和欧洲在内的海外临床研究部分,康方生物则作为承接方推进中国区域的临床研究,且Summit负责支付HARMONi-3研究的全部费用。预计在2028年初这一临床试验才会公布最终数据。

这种情况下,康方生物在国内小试牛刀,拿替雷利珠单抗试试手,就很容易理解了。

不过还有个问题:国内卡瑞利珠单抗、替雷利珠单抗、舒格利单抗等多家PD-1布局过这一适应症。康方生物为何选择百济神州的品种?

上述人士告诉健识局:康方生物的想法可能是挑最强的打。在国内市场,可选的对照药物也就是替雷利珠单抗、信迪利单抗、卡瑞利珠单抗,而其中百济神州的临床做的比较扎实,用替雷利珠单抗来进行对照,谁也不会说康方挑了个软柿子来捏。

在2024年ESMO年会上,百济神州公布的RATIONALE-307四年随访数据显示,替雷利珠单抗联合化疗组均较化疗显著延长了PFS。其中,替雷利珠单抗+紫杉醇及卡铂组的中位OS为26.1个月,患者4年0S率为32.2%,即三分之一患者生存期超过4年。

上述人士告诉健识局:康方生物选择替雷利珠单抗的另一个考量还在于,替雷利珠单抗已经在美国获批上市,众所周知FDA对于临床数据要求较高,这也从侧面验证了临床数据的可靠性,而这对于评价一款药物的效果相当关键。

只挑强者做对手背后

康方生物第二次头对头获胜,其实形式意义更大一些:打消了部分人对依沃西单抗打败K药只是侥幸的担忧。

依沃西单抗头对头战胜K药,其实不少人是有疑问的,关键在于:PD-1联合化疗才是当前的标准疗法,但依沃西单抗打赢的是K药单药。K药很少单打独斗使用,这就好比古代武将本该是骑马对战,但康方选择的是不骑马的步下战。虽然康方赢了,却总觉得双方都没完全发挥出来。

这一次,康方依沃西单抗头对头替雷利珠单抗,算是真正的标准疗法对抗。研究结果显示:依沃西联合化疗组的患者PFS相较对照组,获得了决定性胜出的阳性结果。和对照组相比,依沃西单抗在PD-L1阳性及PD-L1阴性人群中,都显示出了有临床意义的PFS获益。在安全性上,依沃西组也与对照组相似。

康方生物董事长夏瑜在公告中表示:“PD-1联合化疗是当前全球NSCLC的最优一线标准疗法,依沃西在这个领域中再一次以硬核的临床数据,证实了其作为下一代抗肿瘤药物在全球范围内的突破性临床价值和创新竞争力。”

不过,在公告中康方生物并没有提到此次临床试验有关OS的数据。无论替代终点PFS、ORR看起来有多亮眼,OS始终是评价肿瘤药物疗效的金标准。依沃西单抗的全部实力如何,还需要更多更详细的临床数据来证明。

康方生物这一次“秀肌肉”,对于行业里其他品种是有借鉴意义的。不管是在国内还是国外,依沃西单抗都在挑选实力最强劲的对手,这样做的风险固然不小,但也只有和强者头对头胜出,才能在全球市场替代现有标准疗法,获得定价权与市场份额。

2021年11月,CDE发布了《以临床价值为导向的抗肿瘤药物临床研发指导原则》,其中“对照药的选择”中已经明确提到,尽量为受试者提供临床实践中被广泛应用的最佳治疗方式/药物。

在创新药越来越强调回归临床价值的当下,选择实力更强的临床试验药物,进行“头对头”选择也将会是更普遍的情况。

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