2014年8月22日讯 /生物谷BIOON/ --目前，PD-1/PD-L1免疫竞赛异常激烈，市场峰值高达350亿美元，默沙东（Merck）、百时美施贵宝（BMS）、阿斯利康（AZN）、罗氏（Roche）均在火速推进各自的免疫疗法。在《即将结束临床试验的全球重磅药物TOP 15》中，各巨头开发的免疫疗法均有上榜，其中，百时美施贵宝的PD-1抑制剂Opdivo（nivolumab）雄踞榜首，2020年销售预期高达60亿美元。
近日，百时美施贵宝又有了新动作，联手生物巨头新基（Celgene），合作开发nivolumab+Abraxane免疫组合疗法，以彻底挖掘nivolumab的临床潜力。双方于8月20日达成临床合作，计划于第四季度启动一项I期临床研究，调查Opdivo+Abraxane组合疗法治疗多种肿瘤的安全性、耐受性和初步疗效，包括：HER2阴性转移性乳腺癌、胰腺癌、非小细胞肺癌（NSCLC）。
Opdivo（nivolumab）是百时美施贵宝万众瞩目的抗癌免疫疗法，该类疗法旨在利用人体自身的免疫系统对抗癌症，nivolumab是一种PD-1免疫检查点抑制剂，通过阻断PD-1信号通路使癌细胞死亡。Abraxane（注射用紫杉醇[白蛋白结合型]）则是Celgene备受关注的一种化疗药物，因乔布斯之死和癌中之王——胰腺癌适应症而名声大噪，该药能阻止癌细胞的分裂，已被批准用于胰腺癌、前列腺癌、乳腺癌和肺癌的治疗，近来发展势头迅猛。
百时美预计，将nivolumab增强人体免疫的抗癌能力与Abraxane阻止癌细胞分裂的能力融为一体的组合疗法，其协同疗效有望大于2种药物各自单独用药的疗效之和。
此次合作完美符合百时美施贵宝彻底挖掘其明星肿瘤学免疫疗法nivolumab最大临床潜力的野心，耗巨资支持相关组合研究和单药研究。而其他巨头也已启动类似的扩张性、巨资性发展战略，将免疫疗法与各类药物匹配，努力找出最有前途的免疫组合疗法。
虽然可以几乎肯定的是，默沙东的PD-1抑制剂pembrolizumab（MK-3475）会率先登陆美国市场，但百时美施贵宝nivolumab已于今年7月获日本批准，成为全球获批的首个PD-1抑制剂。百时美施贵宝已计划于2014第三季度向FDA提交nivolumab的监管文件，申请的首个适应症为黑色素瘤。如果获批，该药将以品牌名Opdivo上市。
对Celgene而言，该项合作也是一个重要机会。随着全球范围内PD-1/PD-L1免疫疗法的预期获批，该项合作将使Celgene进入数百亿美元的抗癌免疫治疗市场。如果Abraxane能够加强nivolumab的疗效，伴随着百时美施贵宝nivolumab的火爆上市，Abraxane也将得到飞速发展。Abraxane自去年获批用于胰腺癌之后，发展势头迅猛，在2014年第二季度的销售额达到了2.15亿美元，比去年同期增长39%。（生物谷Bioon.com）
英文原文：Bristol-Myers, Celgene pair an immuno-oncology star with a rising chemotherapy
Bristol-Myers Squibb ($BMY) and Celgene ($CELG) are joining forces on a cancer combination treatment, testing the former's highly anticipated immunotherapy in tandem with an on-the-market chemo drug against a host of tumor targets.
The plan is to launch a Phase I study pairing Bristol-Myers' nivolumab, a cancer treatment designed to bring about the death of tumor cells by blocking a pathway called PD-1; and Celgene's Abraxane, an injectable form of the chemotherapy paclitaxel already approved to treat pancreatic, prostate, breast and lung cancers.
The hope is that combining nivolumab's effect on the immune system with Abraxane's ability to halt cancer cell division will result in a therapy greater than the sum of its parts, the companies said, and they plan to kick off their trial in the fourth quarter of this year. Among their targets are HER-2 negative metastatic breast cancer, pancreatic cancer and non-small cell lung cancer.
For Celgene, the study is an opportunity to cut in on the expected multibillion-dollar market expected to come about as PD-1 therapies win approvals around the globe. If Abraxane can bolster the effects of nivolumab, the Big Biotech can hitch its fast-growing cancer treatment to what could be a meteoric launch for Bristol-Myers' contender, which is expected to bring in about $6 billion a year by 2020. (Celgene's treatment has made headway of its own since winning a pancreatic approval last year, growing 39% year-over-year to bring in $215 million in the second quarter.)
The partnership fits right in with Bristol-Myers sweeping development effort for its star oncology candidate, spending big on combination studies and monotherapy trials as it races to cash in on the promise for treatments targeting the lock-and-key proteins PD-1 and PD-L1.
At stake is the largest share of a PD-1 market projected to peak as high as $35 billion a year, and Bristol-Myers is contending with Merck ($MRK), AstraZeneca ($AZN), Roche ($RHHBY) and others with plans to string together FDA approvals and capitalize on stellar data for the whole class. Each contender has mounted a similarly expansive--and expensive--development strategy, mixing and matching immunotherapies in an effort to identify the most promising combinations.
And while Merck is almost certain to hit the U.S. market first with its pembrolizumab, nivolumab became the first PD-1 inhibitor approved anywher in the world when it picked up a Japanese nod last month. Bristol-Myers plans to submit an FDA application for the drug next quarter, targeting melanoma first as it works through late-stage studies in other cancers. If approved, the drug will trade as Opdivo.
