Camlipixant

With no FDA-approved treatments for refractory chronic cough (RCC), patients have long faced limited options – but Trevi Therapeutics is hoping to change that. On Monday, the company announced that its investigational oral therapy Haduvio (nalbuphine extended-release) met its primary endpoint in the Phase IIa RIVER trial, showing a statistically significant 57% placebo-adjusted reduction in 24-hour cough frequency.The crossover study, which enrolled 66 patients with RCC, demonstrated that Haduvio reduced cough frequency by 67% from baseline, compared to 10% with placebo. The therapy also showed similar efficacy in both moderate (10-19 coughs/hour) and severe (20+ coughs/hour) patient subgroups, with reductions of 68% and 66%, respectively.Trevi plans to discuss next steps with the FDA while continuing its parallel Phase IIb CORAL trial in chronic cough associated with idiopathic pulmonary fibrosis (IPF), which recently completed enrollment. Topline results there are due this half."The RIVER trial demonstrated that Haduvio was highly effective, and worked quickly at the lowest dose tested across a broad range of cough counts," said CEO Jennifer Good. "These results, coupled with our existing IPF chronic cough results, are further evidence of the effectiveness of Haduvio's central and peripheral KAMA mechanism in treating these difficult neurological cough conditions." Company shares were up over 41% on the news Monday.While Trevi's success may be capturing investor attention, other players have struggled to gain traction in the space. In 2023, Merck & Co. received a second complete response letter from the FDA for its oral P2X3 receptor antagonist gefapixant, despite the drug being approved in Europe and Japan. The US regulator had concluded that Merck's application "did not meet substantial evidence of effectiveness" for treating refractory or unexplained chronic cough.Meanwhile, GSK is hoping camlipixant, another P2X3 antagonist, can help turn the company's fortunes around (see – Vital Signs: Pharma's worst performers of 2024, and how they can turn the tide in 2025). Phase III results for the drug, which GSK acquired through its $2-billion deal for Bellus Health, are expected at the end of this year.In Phase IIb SOOTHE trial results published earlier this month in the American Journal of Respiratory and Critical Care Medicine, camlipixant demonstrated a 34% placebo-adjusted reduction in 24-hour cough frequency.Before the RIVER readout, Oppenheimer analysts said they "lean optimistic that Haduvio's performance in RIVER will open the door to a sizable second opportunity in RCC patients inadequately addressed by other therapies." Specifically, they highlighted that efficacy in the severe cough segment would "best inform its prospects for those in whom alternatives, including GSK's Phase III-stage camlipixant, are insufficient."

根据恒瑞官网今年1月更新的研发管线，该公司似乎已经放弃了难治性慢性咳嗽（RCC）或不明原因慢性咳嗽（UCC）P2X3拮抗剂项目HRS-2261。 2023年2月，恒瑞在CDE药物临床试验登记与信息公示平台登记了一“HRS-2261治疗难治性慢性咳嗽的有效性和安全性的多中心、随机、双盲、平行、安慰剂对照II期临床研究”（CTR20230367），截至目前试验状态仍旧为“进行中-招募中”。 然而，在此后的短短不足2年里，P2X3拮抗剂领域经历了几起大事件： 2023年4月，葛兰素史克以20亿美元收购BELLUS Health获得camlipixant，将会加速后者该项目的开发速度，也意味着未来该市场又一强劲竞争对手的出现。 2023年12月，默沙东的gefapixant第二次遭FDA拒绝批准，在美国的上市前景变得异常渺茫。 国内P2X3拮抗剂follow者竞争同样激烈，朗来科技的QR-052107B已完成II期临床研究，而豪森的HS-10383也已进入Ⅱ期临床试验中。 很显然，继续开发P2X3拮抗剂或许已经不再符合恒瑞的研发战略了。 延伸阅读：恒瑞10个月把4条呼吸新药管线推进Ⅰ期，加速开拓新治疗领域 本文由「新药前沿」微信公众号根据公开资料整理编辑，欢迎个人转发至朋友圈。媒体或机构转载授权请在「新药前沿」微信公众号留言公众号名称，审核通过后开通白名单获取转载授权，转载请标识来源。 免责声明：本文仅作信息交流之目的，非投资建议或者治疗方案推荐，「新药前沿」微信公众号不对任何主体因使用本文内容而导致的任何损失承担责任。 限于作者水平和专业知识所限，如有谬误，欢迎指正！