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百时美联手FivePrime挖掘明星免疫疗法Opdivo临床潜力

2014-11-26 13:52:27 来源:生物谷

2014年11月26日讯 /生物谷BIOON/ --导读:继今年8月牵手生物技术巨头新基(Celgene),近日百时美施贵宝(BMS)又与FivePrime达成合作,进一步挖掘明星免疫疗法Opdivo的临床潜力。目前,双方已签署了一份独家临床合作协议,评估抗癌免疫疗法Opdivo(nivolumab)与FivePrime单抗药物FPA008组合疗法的安全性、耐受性及初步疗效。Opdivo是百时美的实验性PD-1免疫检查点抑制剂,FPA008则是一种单克隆抗体,抑制细胞集落刺激因子-1受体(CSF1R)。Ia/Ib期研究将评估Opdivo/FPA008作为一种潜在的治疗选择,用于非小细胞肺癌(NSCLC)、黑色素瘤、头颈部癌、胰腺癌、结直肠癌和恶性胶质瘤的治疗。

Opdivo和FPA008均属于癌症免疫疗法的新一类药物,该类药物旨在利用人体自身的免疫系统来对抗癌症。目前,Opdivo已获日本批准用于不可切除性黑色素瘤的治疗,FPA008正处于I期临床,调查用于类风湿性关节炎(RA)和实体瘤的潜在治疗。临床前数据表明,与靶向PD-1或CSF1R的单抗单药疗法相比,抗PD-1/CSF1R抗体组合疗法可能会增强抗肿瘤免疫应答。

当前,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 & Co)、百时美施贵宝(BMS)、阿斯利康(AZN)、罗氏(Roche)是该领域的佼佼者,均在火速推进各自的临床项目。此次竞赛中,百时美和默沙东稍微领先。百时美的PD-1抑制剂Opdivo(nivolumab)于今年7月获日本批准,是全球批准的首个PD-1抑制剂;而默沙东的PD-1抑制剂Keytruda(pembrolizumab)于今年9月初获FDA批准,是美国批准的首个PD-1抑制剂这2种药物获批的首个适应症均为黑色素瘤。

随着各巨头研发项目的推进,PD-1/PD-L1免疫竞赛场地也逐渐从黑色素瘤扩大到乳腺癌、肺癌治疗领域。乳腺癌方面,罗氏和默沙东在三阴乳腺癌(TNBC)临床已取得积极数据;肺癌方面,百时美在欧盟提交了全球首个上市申请,默沙东也赢得了FDA突破性疗法认定。

PD-1/PD-L1免疫疗法是当前备受瞩目的新一类抗癌免疫疗法,旨在利用人体自身的免疫系统抵御癌症,通过阻断PD-1/PD-L1信号通路使癌细胞死亡,具有治疗多种类型肿瘤的潜力,有望实质性改善患者总生存期(OS)。而各大制药巨头也正在火速推进各自的项目,调查单药疗法和组合疗法用于多种癌症的治疗,以彻底发掘该类药物的最大临床潜力。

目前,百时美正在超过50个临床试验中调查Opdivo单药疗法及组合疗法治疗多种肿瘤的潜力。今年8月,百时美牵手新基(Celgene),合作开发Opdivo/Abraxane联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)。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。

英文原文:Five Prime hitches onto Bristol-Myers' blockbuster-in-waiting immunotherapy

Bristol-Myers Squibb ($BMY) has signed a deal with Five Prime Therapeutics ($FPRX) to determine whether a combination of its star immuno-oncology contender and the biotech's antibody can make a difference in a range of cancers.

Under the agreement, Bristol-Myers will hand over $30 million and pay for a Phase I study combining nivolumab, its PD-1 checkpoint inhibitor, with FPA008, Five Prime's treatment targeting a protein called CSF1R. Five Prime is responsible for conducting the trial, which the partners expect to begin next year, looking to establish the safety, tolerability and preliminary efficacy of their medicines in tandem.

Bristol-Myers' therapy is designed to galvanize an immune system attack on tumors by blocking a pathway called PD-1, which, left unchecked, allows cancerous cells to pass undetected. Nivolumab, approved in Japan as Opdivo, is widely considered to be the most promising among a new crop of treatments that block PD-1 or the related PD-L1, a class that includes entries from Merck ($MRK), Roche ($RHHBY) and AstraZeneca ($AZN). Analysts expect the market for such antibodies to peak north of $35 billion a year, estimates driven up by early data suggesting that cancer-treating cocktails featuring checkpoint inhibitors could transform the standard of care for many cancers.

That's where Five Prime comes in. Preclinical data suggest that targeting PD-1 and CSF1R at the same time could lead to a broader anti-tumor immune response than either method alone, the company said, and positive results could help FPA008, once approved, cut in on the explosive sales expected for nivolumab. Five Prime's shares rose more than 18% on the announcement Monday morning.

On its own, FPA008 is in the midst of a Phase I trial in rheumatoid arthritis, and Five Prime believes it has potential as a monotherapy for solid tumors, idiopathic pulmonary fibrosis, lupus nephritis and other inflammatory disorders.

In the meantime, the biotech has the benefit of fleshing out FPA008's potential on Bristol-Myers' dime, putting the combo up against on-small cell lung cancer (NSCLC), melanoma, head and neck cancer, pancreatic cancer, colorectal cancer and malignant glioma.

"(Bristol Myers') vision aligns with our commitment to advancing promising immune-modulating targets, alone or in combination, to create next-generation immunotherapies for cancer patients," Five Prime CEO Lewis Williams said in a statement. "We look forward to initiating this study and expanding the development of FPA008 as a potential immunotherapy for these 6 types of cancer."

Meanwhile, Bristol-Myers is racing to the FDA with its PD-1 blocker, planning to hand in a melanoma application this quarter, well ahead of Wall Street's expectation of a mid-2015 submission. The company is also working through a rolling FDA submission for nivolumab in NSCLC, expecting to complete that filing by year's end. The company's sweeping clinical program for nivolumab includes more than 50 trials, investigating the drug in renal cell carcinoma, head and neck cancer, glioblastoma, and non-Hodgkin lymphoma, among other malignancies.

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