Centre Hospitalier Universitaire de Rouen

The Reblozyl trial flop adds to a concerning trend of clinical woes at Bristol Myers Squibb this year. Despite a phase 3 flop, Bristol Myers Squibb—encouraged by “clinically meaningful results” and bruised by three other recent pivotal trial failures—still plans to discuss a potential approval filing with the FDA for the company’s Reblozyl.Friday, the New Jersey pharma announced that a phase 3 study evaluating Reblozyl in patients with myelofibrosis-associated anemia who required red blood cell transfusions did not meet its main goal. The patients were also on background treatment with a JAK inhibitor such as Incyte’s Jakafi.The trial, coded Independence, failed to show a statistically significant difference for Reblozyl versus placebo in freeing patients of transfusions during a consecutive 12-week period, starting within the first 24 weeks of treatment.The P-value for the primary endpoint’s analysis landed at 0.0674, narrowly missing the maximum 0.05 threshold that’s typically considered statistically significant. The exact bar for this trial is unclear.Nevertheless, BMS noted that the data favored Reblozyl, with the drug showing a “numerical and clinically meaningful improvement” in transfusion independence, in line with previous findings from a phase 2 study.Several secondary measures also showed a “clinically meaningful” benefit for the BMS drug, according to the company. These include a higher number of patients who achieved at least a 50% reduction—and by at least four red blood cell units—in transfusion burden.However, the company’s July 18 release didn’t mention how Reblozyl fared on the trial’s key secondary endpoint, which is weighing the number of patients who became transfusion-independent over any consecutive 16-week period, beginning within 24 weeks of treatment. In response to a Fierce Pharma request for clarification, a BMS spokesperson said the company plans to share full data from the study in a future peer-reviewed setting. Based on the data, BMS said it will engage with the FDA and the European Medicines Agency about potentially applying for marketing approvals. The company believes “the totality of these results, including meaningful improvements in transfusion burden and hemoglobin levels, support the potential to address an unmet need in patients who have few treatment options,” Anne Kerber, BMS’ head of development in hematology, oncology and cell therapy, said in a July 18 release.The Reblozyl trial flop adds to a concerning trend of clinical woes at BMS this year. All four of the pivotal life-cycle management trials that have read out this year for BMS’s existing drugs have turned up negative.The losing streak started in February with the LAG-3/PD-1 combo Opdualag flunking as an adjuvant treatment for resected stage 3 or 4 melanoma. Then, the heart med Camzyos couldn’t move the needle in non-obstructive hypertrophic cardiomyopathy.A few days later, the company’s Cobenfy stumbled as an adjunctive treatment for inadequately controlled schizophrenia. That leaves the closely watched Adept-2 trial for Cobenfy in Alzheimer’s disease psychosis as the only planned phase 3 readout this year for an in-market BMS drug that has not reported outcomes.The pivotal success drought is troublesome because all those four drugs have been tasked with helping BMS navigate a huge patent cliff. During a presentation at the J.P. Morgan Healthcare Conference in January, BMS CEO Chris Boerner highlighted the four drugs, plus the CAR-T therapy Breyanzi, as five products key to the company’s growth portfolio, which was expected to exceed 50% of BMS’s revenues in 2025. Reblozyl is already approved by the FDA to treat two other types of anemia related to beta thalassemia and lower-risk myelodysplastic syndromes (MDS).  BMS has projected the drug, acquired in its Celgene buyout, can reach $4 billion or more in peak sales. In the first quarter of 2025, Reblozyl sales jumped 35% year over year, reaching $478 million.It’s not the end of the road for the first-in-class erythroid maturation agent. While BMS shoots for potential submissions in myelofibrosis-associated anemia, the phase 3 Element-MDS trial testing Reblozyl in nontransfusion-dependent MDS anemia is expected to read out in 2027. And the drug is also being evaluated in alpha thalassemia.Elsewhere in the myelofibrosis universe, Novartis recently took a hit as a safety signal has delayed—if not completely derailed—the Swiss pharma’s regulatory plan for its BET inhibitor candidate pelabresib, which was obtained from its $2.9 billion MorphoSys buyout.Incyte recently shared phase 1 data for its BET inhibitor INCB057643, used with or without Jakafi, in patients with relapsed or refractory myelofibrosis and other myeloid neoplasms. The company recently scrapped development of its ALK-2 inhibitor zilurgisertib in myelofibrosis-related anemia after a failed phase 1/2 trial.Editor's Note: The story was updated with a BMS response to Fierce's inquiry. 

自安进公司斥资近20亿美元收购Five Prime公司及其针对FGFR2b的单克隆抗体（mAb）以来，已过去四年多。如今，贝马妥珠单抗（bemarituzumab）的新数据证明了安进公司这一决策的正确性。6月30日，安进公司公布了一项胃癌III期临床试验的主要结果，显示该单克隆抗体达到了主要生存终点。尽管这家制药公司未透露此次临床试验成功的具体细节，但承诺会在未来的医学会议上提供详细数据。这项名为FORTITUDE-101的III期临床试验共招募了547名患有不可切除、局部晚期或转移性非HER2阳性、FGFR2b过表达的胃癌或胃食管交界处（GEJ）癌的患者。参与者被随机分组，一组接受一线贝马妥珠单抗联合化疗（mFOLFOX6方案）治疗，另一组仅接受化疗。根据预先设定的中期分析结果，联合治疗组在总生存期（OS）方面相比单纯化疗组，取得了具有统计学意义和临床意义的显著改善，达到了试验的主要终点。安进公司负责研发的执行副总裁杰伊·布拉德纳（Jay Bradner）表示：“大多数胃癌患者在确诊时已处于晚期，预后较差，生存率低，且治疗选择有限。”他补充道，此次研究结果“标志着在开发有效胃癌靶向治疗药物方面取得了具有重大意义的进展”。此次结果也印证了II期临床试验的发现。在II期试验中，贝马妥珠单抗联合化疗相较于单纯化疗，显著延长了患者的无进展生存期和总生存期。II期试验也显示，接受贝马妥珠单抗治疗的患者角膜和口腔炎等不良事件（AEs）的发生率更高。实验药物组中至少出现3级不良事件的患者比例达82.9%，而安慰剂组为74%。此外，34.2%接受贝马妥珠单抗治疗的患者因不良事件而中断治疗，而安慰剂组仅为5.2%。在III期试验中，贝马妥珠单抗组眼部不良事件的发生“频率更高，严重程度也更高”。超过四分之一接受该单克隆抗体治疗的患者出现了视力下降、点状角膜炎、贫血、中性粒细胞减少、恶心、角膜上皮缺损或干眼等症状。FORTITUDE-101试验得到了再鼎医药的支持。2017年，再鼎医药从Five Prime公司独家获得了贝马妥珠单抗在中国大陆、香港、澳门和台湾地区的共同开发与商业化权利。此外，双方合作伙伴还在开展一项贝马妥珠单抗联合化疗及百时美施贵宝公司的纳武利尤单抗（Opdivo，商品名）作为胃癌一线治疗的III期试验，预计今年下半年公布数据。药事纵横投稿须知：稿费已上调，欢迎投稿