Ensifentrine

A chronic obstructive pulmonary disease approval marks Nucala's fifth in the U.S. While GSK’s Nucala may not have earned the distinction of becoming the first FDA approved biologic for chronic obstructive pulmonary disease (COPD), the British drugmaker is confident its IL-5 antibody still has a major role to play in tackling the traditionally tough-to-treat respiratory condition.Now, following an unexpected delay earlier this month, the company has a fresh FDA green light to put its thesis to the test.The FDA on Thursday approved Nucala as an add-on maintenance treatment for adults with inadequately controlled COPD and an eosinophilic phenotype. The thumbs-up makes Nucala (mepolizumab) the second biologic approved for the disease and the third new COPD therapy to score approval in the U.S. in less than a year.Notably, the FDA approved Sanofi and Regeneron’s immunology juggernaut Dupixent in the indication in September, while Verona Pharma’s Ohtuvayre received the regulatory all-clear last June. Dupixent and Ohtuvayre aren’t in direct competition given that Ohtuvayre is cleared in patients with persistent shortness of breath, while Dupixent is suited for COPD patients with persistent exacerbations.That said, Nucala and Dupixent will likely butt heads in the space following GSK’s launch, given that Dupixent's label covers a similar eosinophil-high patient population.Eosinophils, which are a type of white blood cell, serve as a biomarker for type 2 inflammation and help determine the risk of COPD exacerbations, GSK explained in a release.  COPD—which includes chronic bronchitis and emphysema—is a progressive inflammatory lung disease that causes breathing problems. The condition is one of the leading causes of death in the U.S. alongside heart disease and cancer. While it is mainly caused by smoking, nonsmokers are also susceptible, according to the Centers for Disease Control and Prevention.Inhaled triple therapies have been around to treat COPD for some time, but many patients on those standard-of-care treatments continue to experience persistent symptoms and exacerbations, GSK has said.In turn, the need for additional treatment options remains crucial, Luke Miels, GSK’s chief commercial officer, said on a media call ahead of the FDA’s decision.The GSK exec described patients in Nucala’s phase 3 Matinee study in COPD as being “maxed out" on standard of care. The trial findings suggest the IL-5 antibody can offer patients a “material improvement” while also keeping them out of the hospital, according to Miels.Sizing up the competition Miels figures Nucala will be an enticing option for doctors treating COPD patients given the breadth of the patients who participated in Matinee.GSK’s phase 3 trial recruited COPD patients with chronic bronchitis, emphysema only or both, which can “sometimes be difficult to separate,” Miels said. Conversely, the late-stage trials that supported Dupixent's COPD approval in September included patients who had chronic bronchitis and emphysema or bronchitis alone, but not emphysema only patients, Miels noted.“We had the widest population, which is important because for a physician to stratify these patients, it’s much simpler to be able to say, ‘OK, I can use Nucala in patients whether they’ve got emphysema, chronic bronchitis or both,’” he explained.GSK is also playing up Nucala’s ability to help COPD patients avoid hospitalization, which often marks a severe turn in a person’s prognosis.Around 1 in 4 COPD patients who are hospitalized end up dying within a year, while roughly half of patients who are hospitalized will likely die within five years, Miels said.“There’s a very high burden when you have severe exacerbations and end up being hospitalized,” Miels said. “So, the aim is to keep patients out of the hospital, keep them stable and keep them at home.”In the Matinee study that helped secure Nucala’s approval, the interleukin inhibitor led to a 21% reduction in the annualized rate of moderate or severe COPD exacerbations versus placebo, hitting its primary endpoint, GSK said in a data drop late last month. GSK’s drug also curbed the annualized rate of moderate or severe exacerbations compared to placebo by 31% in patients who only have chronic bronchitis.Nucala also cut patients’ yearly rate of exacerbations leading to emergency room visits and hospitalizations by 35% in one of the trial’s main secondary endpoints, GSK added.The study found that adverse events were largely on par between Nucala and placebo, with the most common issues patients faced including exacerbation or worsening of their COPD.Matinee specifically assessed Nucala in COPD patients with evidence of type 2 inflammation confirmed via high blood eosinophil count. Nucala's approval was also bolstered by older results from the late-stage Metrex study, which pitted the drug against placebo both in COPD patients with an eosinophilic phenotype and those without. While the indication is new territory for Nucala, GSK is no stranger to COPD and currently boasts the “largest product in COPD today” by way of its triple-therapy inhaler Trelegy Ellipta, Miels said. Nevertheless, the company is planning further outreach and education efforts for both doctors and patients in the wake of Nucala’s FDA nod, Miels said.The COPD approval marks the fifth Nucala has received from the FDA, following green lights in severe asthma, chronic rhinosinusitis with nasal polyps, eosinophilic granulomatosis with polyangiitis and hypereosinophilic syndrome.Meanwhile, Thursday's approval came two weeks after the FDA missed its original target decision date for Nucala in COPD. GSK had originally expected to hear a verdict on its filing by May 7. On GSK's media call earlier this month, Miels noted that the company plans to “essentially keep the same pricing structure that we already have” with Nucala, which currently costs around $3,800 for a single dose for injection in the U.S. before discounts. The company expects Nucala to hit 500 million pounds sterling (roughly $669 million) in peak year sales for COPD, Miels noted.For all of 2024, Nucala sales across its prior four indications grew (PDF) by 13% at constant currencies to 3.3 billion pounds ($4.4 billion). The drug generated (PDF) 444 million pounds ($594 million) in 2025’s first quarter, a 21% increase over the sum it delivered for the same period last year. 

近日，优锐医药（Nuance Pharma）宣布恩司芬群Ensifentrine在中国开展的COPD三期临床试验ENHANCE-CHINA取得积极顶线结果。该药于2024年6月首次在美国获批上市，是COPD治疗领域近20年以来首个获批上市的新机制吸入制剂，上市8个月累计销售额已达到1.14亿美元。ENHANCE-CHINA是一项针对中国患者的随机、双盲、安慰剂对照临床试验（n=526），该试验成功达到主要终点及多项次要终点。主要终点（FEV1 AUC 0-12h）：第12周时，恩司芬群组较安慰剂组的基线校正平均FEV1曲线下面积（0-12小时）改善110 mL（p<0.0001）。次要终点：第12周峰值FEV1较安慰剂增加174 mL（p<0.0001），晨间谷值FEV1和晚间谷值FEV1分别较安慰剂增加36 mL（p=0.0533）和65 mL（p=0.0038），0-4小时和6-12小时平均FEV1较安慰剂分别增加162 mL（p<0.0001）和77 mL（p=0.0003）。此外，恩司芬群组24周内中重度COPD急性加重率较安慰剂组降低28%（RR=0.72，95%CI：0.43-1.22），首次中重度急性加重时间风险降低25%（HR=0.75，95%CI：0.44-1.28）。在呼吸困难改善、患者生活质量、呼吸症状评分方面也有改善。安全性方面，恩司芬群耐受性良好，治疗相关不良事件发生率与安慰剂相似。优锐医药计划在2025年下半年向NMPA提交新药申请，此前该药已在澳门获批、并在海南博鳌乐城先行区落地，中国市场商业化进程加速。1.全新机制慢性阻塞性肺疾病（COPD,chronic obstructive pulmonary disease）简称慢阻肺，是一种严重的慢性呼吸系统疾病。根据世界卫生组织统计，COPD是人类的第三大死因，我国就有近1亿COPD患者，40岁以上成人COPD患病率达13.7%。目前，COPD的治疗药物主要有吸入性糖皮质激素、支气管扩张剂、磷酸二酯酶-4抑制剂、抗生素、黏液溶解剂及抗氧化剂。但这些药物多为使用多年的“老药”，且仍有部分患者的COPD急性加重难以控制，存在巨大的临床未满足需求。恩司芬群（Ensifentrine，Ohtuvayre）是Verona Pharma开发的一款全球首创的磷酸二酯酶3/4（PDE3/4）抑制剂，其对PDE3和PDE4的双重抑制可产生叠加或协同效应，从而增强对支气管扩张、气道炎症和黏膜纤毛清除的作用。使用上，该产品通过标准喷射雾化器直接进入肺部，无需高吸入气流或复杂的手呼协调。2024年6月，该药获美国FDA批准上市，作为维持疗法治疗慢性阻塞性肺病（COPD）成人患者，成为二十年来首个获批的COPD新机制吸入剂，为COPD治疗领域注入新活力。图片来源：Verona Pharma美国FDA的批准是基于ENHANCE-1和ENHANCE-2两项三期临床研究数据，Ensifentrine在肺功能、生活质量、急性加重风险方面都有改善。图片来源：Verona Pharma凭借新机制和在COPD患者群体的广泛适用性，Ensifentrine上市后销售额快速增长，8个月累计销售额已超过1亿美元，仅2025Q1销售额就达到了7130万美元。而且，Verona Pharma还在探索Ensifentrine用于治疗非囊性纤维化支气管扩张、囊性纤维化和哮喘等适应症。Verona Pharma还开发了Ensifentrine+LAMA(Nebulizer)固定剂量组合疗法，以及ensifentrine吸入粉雾剂(DPI)和定量吸入气雾剂(MDI)。未来呼吸领域大品种预定。在中国，2021年，优锐医药从Verona Pharma引进Ensifentrine在大中华区（中国大陆、香港、澳门和台湾）临床开发与商业化的独家权利，潜在交易总金额高达2.19亿美元。本次ENHANCE-CHINA研究结果证明，恩司芬群在中国患者中同样表现出肺功能显著改善、生活质量改善，以及急性加重风险降低趋势。优锐医药计划于今年下半年向NMPA提交新药申请，上市进程进入倒计时。此前，恩司芬群已于去年12月通过海南博鳌乐城先行先试项目落地中国，今年2月又在澳门获批用于成人COPD维持治疗。2.国产已在路上Ensifentrine的成功上市及优秀的商业化表现，打破了COPD治疗僵局，也开启了PDE3/4抑制剂研发热潮。药智数据显示，目前国内已有多家药企布局PDE3/4抑制剂，其中正大天晴的TQC3721、海思科的HSK39004和恒瑞医药的HRS-9821三款已进入临床阶段。TQC3721TQC3721吸入混悬液由正大天晴开发，是国内研发进度最快的国产PDE3/4抑制剂（用于治疗中重度慢性阻塞性肺病），目前位于全球进度第二。去年，TQC3721吸入混悬液两项研究成果登上欧洲呼吸学会国际大会（2024 ERS），其IIa期临床数据显示其有同类最优的潜力，预计2025年启动治疗慢阻肺病（COPD）的3期临床。同时正大天晴还开发了该产品的吸入粉雾剂剂型，目前也已处于治疗COPD的1期临床阶段。HSK39004海思科的HSK39004也开发了吸入混悬液和吸入粉雾剂两种剂型。临床前研究结果显示，HSK39004在离体气管环和体内疾病模型中表现出显著的气道舒张和抗炎作用，且安全性良好。药智数据显示，海思科已登记一项评价HSK39004吸入混悬液和HSK39004吸入粉雾剂治疗慢性阻塞性肺疾病（COPD）的药代动力学、有效性和安全性的多中心、随机、双盲、安慰剂对照、平行设计的Ⅱ期临床研究。HRS-9821恒瑞医药的HRS-9821吸入混悬液已在去年获批临床试验默示，适用于慢性阻塞性肺疾病(COPD)的维持治疗。3.结语Ensifentrine的上市打破了COPD领域多年无新机制药物的僵局，预计这一突破性药物很快也将惠及国内患者。除了PDE3/4抑制剂，生物制剂也在COPD治疗领域撕开了口子，赛诺菲和再生元的达必妥（度普利尤单抗）已在美国、欧洲、中国及日本获批用于COPD治疗，GSK的Nucala（美泊利珠单抗）也已提交COPD适应症的上市申请，未来，或许还有更多新机制创新药上市，为COPD患者带来治疗希望。#COPD #呼吸 #创新药 参考资料：1.https://www.prnewswire.com/apac/zh/news-releases/ensifentrinecopdenhance-china-302459815.html2.Verona Pharma公司官网3.药智数据4.正大天晴2款创新药首登呼吸医学全球盛会https://mp.weixin.qq.com/s/bFp2DGxJdiNiI3luo8FKgA声明：本内容仅用作医药行业信息传播，为作者独立观点，不代表药智网立场。如需转载，请务必注明文章作者和来源。对本文有异议或投诉，请联系maxuelian@yaozh.com。责任编辑 | 小月石合作、投稿、转载开白 | 马老师 18323856316（同微信） 阅读原文，是受欢迎的文章哦