默沙东黑色素瘤药物Lambrolizumab获FDA“突破性疗法”资格

    黑色素瘤通常与过度暴露于紫外线有关，根据美国国家癌症研究所的数据，2013年美国预期会出现76690新病例，其中9480名患者会因此死亡。
    突破性疗法资格的获得使lambrolizumab(代号 MK-3475)引起众人关注，授予lambrolizumab这一资格意味着FDA认可该治疗药物对威胁生命的疾病表现出明显收益，而且超过了现有治疗药物。
突破性疗法称号是2012年FDA安全和创新法案中制定的部分内容，目的是帮助加快严重致命性疾病潜在新药的开发进度，以尽早给患者带来所需的治疗药物。业内观察人士已将该资格视为一种认可，如辉瑞的乳腺癌药物Palbociclib、强生和Pharmacyclics公司用于治疗血癌的候选药物 Ibrutinib、Vertex制药用于囊性纤维化治疗的VX-809和Kalydeco，以及诺华用于肺癌治疗的药物LDK378。
    默沙东正在为LambrolizumabII期随机临床试验招募患者，试验中将对比两种不同剂量的药物和化疗对晚期黑色素瘤治疗效果。去年9月份，默沙东报告说，参与Ib临床试验的85名患者，有51%的患者表现出抗肿瘤响应，有9%的患者在第12周或12周之后表现出完全响应。
Lambrolizumab以一种PD-1为靶点，后者可以欺骗免疫系统将肿瘤细胞作为正常细胞处理，使肿瘤细胞逃离免疫系统的攻击，以PD-1为靶点，Lambrolizumab可以恢复免疫细胞攻击肿瘤细胞的能力。
与黑色素瘤相关的拓展阅读：

• JCO：新研究揭示转移性黑色素瘤对威罗菲尼的耐药机制
• JNCI：PAK1抑制剂能有效治疗BRAF野生型黑色素瘤患者
• Cancer：阿司匹林可降低黑色素瘤发病风险
• NAT GENET ：肥胖基因或是黑色素瘤的风险因素
• JNCI：HIV阳性者非黑色素瘤皮肤癌发病率高
• JCO:索拉非尼对转移性黑色素瘤无益
更多信息请点击：有关黑色素瘤更多资讯

Merck scores 'breakthrough' status from FDA for immunotherapy against melanoma
Merck ($MRK) has a shot at a speedy development path for lambrolizumab. The FDA has pinned a "Breakthrough Therapy" tag on the experimental antibody drug for advanced melanoma, based on Phase Ib data that showed significant early signs of antitumor activity in some patients with aggressive cases of the deadly skin cancer.
Often linked to too much exposure to ultraviolet rays, melanoma is expected crop up in 76,690 new cases and kill 9,480 patients in the U.S. in 2013, according to data from the National Cancer Institute.
The breakthrough recognition pushes lambrolizumab (codenamed MK-3475) into the spotlight, just where Merck wanted the antibody when the company requested that designation from U.S. regulators last year. In bestowing breakthrough status to a drug, the FDA acknowledges that the therapy has shown early evidence of significant benefits over existing therapies for life-threatening illnesses. However, the FDA only began selecting programs for the designation this year, and it's unclear how exactly the agency will handle reviews of drugs with the coveted status.
Yet the agency places the breakthrough program among others intended to bring therapies to patients in need earlier. And industry watchers have regarded the status as an endorsement of sorts for previous breakthrough designees such as Pfizer's ($PFE) breast cancer contender palbociclib, Johnson & Johnson ($JNJ) and Pharmacyclics' ($PCYC) candidate ibrutinib for blood cancers, Vertex Pharmaceuticals' ($VRTX) VX-809 and Kalydeco for cystic fibrosis, and Novartis' ($NVS) LDK378 for lung cancer.
"We are pleased that the FDA has designated lambrolizumab a Breakthrough Therapy for patients with advanced melanoma," said Dr. Gary Gilliland, senior vice president and oncology franchise head, Merck Research Laboratories, in a statement. "The FDA's decision to place lambrolizumab in a category that may enable expedited development and review is an important milestone for Merck as we advance ongoing programs in multiple cancer indications."
Merck is recruiting patients for a randomized Phase II trial of lambrolizumab, comparing two different doses of the drug and chemotherapy in advanced melanoma. In November, the U.S. drug giant reported that 51% of 85 patients in a Phase Ib study showed an objective antitumor response and 9% had a complete response at or after 12 weeks. It also showed antitumor activity in 11, or 41%, of patients who had received the gold-standard advanced melanoma med Yervoy from Bristol-Myers Squibb ($BMY).
The breakthrough status follows a letdown last year for Merck's oncology pipeline, which was hit with an FDA rejection on the sarcoma drug ridaforolimus. It was one of the R&D setbacks leading up to Merck CEO Kenneth Frazier's move earlier this year to bring in ex-Amgen ($AMGN) R&D boss Roger Perlmutter to head research at the drug giant and revive the pipeline.
Lambrolizumab, which Merck has begun to study in lung cancer and other tumors, targets a "molecular camouflage" receptor called PD-1 that tricks the immune system into treating cancer cells as normal ones to evade the immune attacks, Merck spokeswoman Caroline Lappetito told FierceBiotech in an interview. By targeting PD-1, lambrolizumab could restore the ability of immune cells to battle cancer. {nextpage}