Ensifentrine

赛诺菲/再生元的Dupixent（dupilumab）和Verona的Ensifentrine最近向美国食品药品管理局（FDA）提交了上市申请，这意味着2024年将出现两种治疗慢性阻塞性肺病（COPD）的新疗法。据GlobalData称，这一轮潜在的新疗法浪潮将带来COPD治疗模式的转变。GlobalData预测，到2029年，Dupixent的全球总销售额将达到214亿美元，而ensifentrine的销售额也将达到11亿美元。COPD标准疗法（SoC）包括短效或长效β2受体激动剂或毒蕈碱拮抗剂作为单一疗法或联合疗法。对于病情加重者，还可添加吸入皮质类固醇（ICS）作为三联疗法，或与长效β-2受体激动剂一起作为固定剂量的联合疗法。根据COPD的严重程度，磷酸二酯酶抑制剂（PDE）可作为三联疗法的附加疗法。患者可以耐受这些疗法；然而，COPD的进展性使患者需要在使用SoC的同时进行额外的维持治疗。目前COPD市场的空白在于缺乏生物药。不过，赛诺菲/再生元的白细胞介素-4和白细胞介素-13抑制剂Dupixent有可能弥补这一空白，因为BOREAS和NOTUS两项III期临床试验都报告了积极的结果，而且这两项试验的主要终点都达到了要求。试验结果表明，与安慰剂相比，Dupixent在BOREAS试验中能显著减少中度或重度COPD急性加重，52周内减少30%，在NOTUS试验中减少34%，并在12周时改善肺功能，且这种改善能持续52周。这两项临床试验的积极结果促使Dupixent的补充生物制品许可申请（sBLA）被美国食品药品管理局（FDA）接受，作为一种附加的维持疗法。Dupixent用于COPD（COPD）的《处方药用户费法》（PDUFA）定在2024年6月27日。根据公司公告，欧盟和中国的监管申请也在审查之中。如果获得批准，COPD将成为Dupixent的第六个适应症。该疗法目前已被批准用于特应性皮炎、哮喘、嗜酸性粒细胞性食管炎、结节性瘙痒症和伴有鼻息肉的慢性鼻炎。至于Verona的Ensifentrine，是一种以雾化吸入给药的首创PDE3/4双靶点抑制剂，在两项积极的III期试验（ENHANCE-1和ENHANCE-2）达到减少病情恶化和改善肺功能的主要终点。2023年9月，FDA受理ensifentrine用于COPD患者的维持治疗的上市申请。PDUFA日期为2024年6月26日，而且FDA未计划召开咨询委员会会议讨论该申请。COPD晚期市场前景广阔，生物制剂和新型同类首创双重磷酸二酯酶抑制剂可能会在今年进入市场。接受GlobalData采访的KOL们表示，Dupixent和Ensifentrine获批几成定局，COPD领域几十年来从未出现过这种情况。参考：globaldata，企业公告等本文由「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！

Pictured: Illustration of lungs with syringes/Nicole Bean for BioSpace Potential FDA approvals this year of Sanofi and Regeneron’s Dupixent (dupilumab), as well as Verona Pharma’s ensifentrine, could change the treatment paradigm for chronic obstructive pulmonary disease, according a new report from analytics firm GlobalData. Dupixent is poised to address the notable gap in biologic treatments for chronic obstructive pulmonary disease (COPD) and target its underlying inflammatory pathway by blocking the IL-3 and IL-4 cytokines, according to the analysis. Meanwhile, Verona’s ensifentrine introduces a new mechanism by inhibiting both the phosphodiesterase 3 and 4 enzymes to ease exacerbations. “The COPD late-stage market looks extremely promising,” GlobalData pharma analyst Asiyah Nawab said in a statement, adding that their modes of action and promising clinical data could facilitate their “penetration into the market this year.” According to COPD experts interviewed by GlobalData, “the pipeline for COPD is extremely positive, with Sanofi/Regeneron’s Dupixent and Verona’s Ensifentrine having a high chance of being licensed.” The experts also noted that the COPD space “has not been in this position for decades.” Sanofi and Regeneron’s Dupixent—currently approved for atopic dermatitis, asthma, prurigo nodularis, eosinophilic esophagitis and chronic rhinosinusitis with nasal polyps—is a monoclonal antibody that blocks the IL-3 and IL-4 cytokines reducing type 2 inflammation, a key driver in several immune-mediated conditions. The partners are proposing Dupixent as a COPD treatment using results from the Phase III BOREAS and NOTUS trials. Data from BOREAS, published in May 2023, demonstrated that adding Dupixent to standard of care could reduce moderate or severe exacerbations by 30% over 52 weeks. The therapeutic antibody could also boost lung function and health-related quality of life while lowering symptom severity. In NOTUS, Dupixent reduced moderate or severe acute exacerbations by 34% over 52 weeks of follow-up, while also improving lung function. The FDA in February 2024 accepted the supplemental Biologics License Application for Dupixent and granted it Priority Review. The decision is due by June 27, 2024. Verona’s ensifentrine is also undergoing regulatory review. The FDA accepted its New Drug Application in September 2023 and has set a target action date of June 26, 2024. Ensifentrine is backed by data from the Phase III ENHANCE trials, which found that the candidate reduced the risk of COPD exacerbations while also improving lung function and easing symptoms. In January 2024, Verona secured $400 million in financing from Oxford Finance and Hercules Capital, which the biotech will use to fund the launch of ensifentrine. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.