Beclometasone Dipropionate

Patients with chronic obstructive pulmonary disorder in the U.S. have the first treatment option with a novel mechanism of action in more than a decade after the FDA signed off on Verona Pharma’s Ohtuvayre. Thirteen years after his passing, Sir David Jack still looms as an innovative force in healthcare. Wednesday, when the FDA approved Verona Pharma’s Ohtuvayre (ensifentrine) to treat chronic obstructive pulmonary disorder (COPD), it was a reminder of the extraordinary touch Jack had in creating treatments for respiratory disorders. The pharmacologist, who was born 100 years ago, discovered ensifentrine four decades ago when he was the R&D chief at GSK. The compound, then known as RPL554, struggled to make its mark after Jack retired in 1987. Nineteen years after Verona was established to unlock ensifentrine’s potential—and after RPL554 has undergone nearly 20 clinical trials in COPD—Verona has finally pushed Ohtuvayre across the finish line as the first commercial product for the London-based company. Ohtuvayre becomes the first novel treatment advance in more than a decade for COPD, an inflammatory condition that restricts airflow from the lungs and leaves patients struggling to breathe. Ohtuvayre is approved as a monotherapy or as an add-on medicine with current therapies. As a selective dual inhibitor of the phosphodiesterase 3 (PDE3) and phosphodiesterase 4 (PDE4) enzymes, Ohtuvayre combines two properties in one medicine, setting it apart in COPD for its ability to both open the airways of patients and reduce their inflammation. “It’s really the first novel mechanism as an inhaled therapy in over 20 years for COPD,” David Zaccardelli, Verona’s CEO, said in an interview with Fierce Pharma. “We believe its bronchodilator and non-steroidal anti-inflammatory activity has the potential to change the treatment paradigm.” Ohtuvayre is administered twice daily by a jet nebulizer, with sessions lasting between five minutes and seven minutes. Verona Chief Commercial Officer Chris Martin said the company doesn’t expect the administration method to affect uptake much as roughly half of COPD patients already use hand-held devices. “Some use them for chronic maintenance and a lot of patients use them for rescue. These patients are extraordinarily comfortable with using a nebulizer,” Martin said. “Unfortunately, with many of these patients, their [physical] activity levels are so much lower than yours or mine, that a nebulization is not a big burden on their [daily] activities.”   Therapies commonly used to control COPD are inhaled corticosteroids, which reduce inflammation, and bronchodilators, which relax muscles in the lungs and widen the airways. Bronchodilators include long-acting beta agonists (LABAs) and long-acting muscarinic agonists (LAMAs). Some COPD patients are on a regimen with all three treatments. Others, who can’t take corticosteroids, use a LAMA and LABA mix. “One of the things that’s been really exciting in the research is the idea that patients sometimes are a little nervous about steroids,” Martin said. “This non-steroidal bronchodilator, non-steroidal anti-inflammatory is extraordinarily appealing to them.” Two clinical trials have shown that Ohtuvayre performs well alone or along with current maintenance therapies. The drug is most effective on patients who are still symptomatic after using a LAMA and LABA combo. The phase 3 ENHANCE-I and ENHANCE-II trials met their primary endpoints by showing that Ohtuvayre improved lung function. Pooled analysis of the two studies also showed that Ohtuvayre reduced flare-ups through 24 weeks by 40% in patients with moderate to severe COPD. Verona will charge $2,950 for a monthly dose of Ohtuvayre. The $35,400 annual price exceeds the cost-effectiveness threshold (PDF) of between $7,500 and $12,700 per year established by The Institute for Clinical Economic Review (ICER), which assesses the value of pharmaceutical products. “Current evidence shows that ensifentrine decreases exacerbations when used in combination with some current inhaled therapies and is well-tolerated by patients, but there are uncertainties about how much benefit it may add to unstudied combinations of inhaled treatments,” David Rind, M.D., ICER’s chief medical officer, said in a release. Verona plans to launch Ohtuvayre in the third quarter of this year. The date will be significant as Regeneron and Sanofi are expected to land a highly anticipated approval for Dupixent to treat COPD, with a delayed FDA target decision date of Sept. 27. The companies were originally expecting a verdict on June 27, but it was pushed back three months as regulators asked for additional data on two trials that have set Dupixent up for approval. Three months ago, analysts at Evercore ISI projected that a COPD nod would add a potential sales boost of $3.5 billion annually for Regeneron and Sanofi’s megablockbuster, bringing its peak sales potential to $20 billion.  As for Ohtuvayre, analysts see it achieving blockbuster status quickly, with GlobalData estimating sales to reach $1.05 billion by 2029. It’s a recognition of the unmet need in the indication and the massive population that a differentiated treatment could serve. In the U.S., 8.6 million patients are treated for chronic symptoms of COPD. More than 390 million people worldwide are living with COPD. “We believe the indication for ensifentrine is broad. It allows the physician to use it across that 8.6 million spectrum,” Martin said. “What we hear in our research is that doctors are looking for new therapeutic options for patients who are persistently symptomatic. What we see across a variety of different studies is at least half the patients treated today remain persistently symptomatic and are dissatisfied with current therapies.” A fixed-dose combination of Ohtuvayre and the LAMA glycopyrrolate is currently under development for the maintenance treatment of COPD. Ohtuvayre also has potential to be developed for cystic fibrosis, non-cystic fibrosis bronchiectasis, asthma and other respiratory diseases.   With a market cap of $1.27 billion and an FDA-approved therapy, Verona could be viewed as a potential buyout target, and GSK would be a good fit, given its experience with respiratory disease treatments. If that came to pass, it would bring ensifentrine full circle, back to the company where it was established by Jack, who also discovered blockbuster asthma drug Advair and the first inhaled steroid beclomethasone. EDITOR'S NOTE: The price Verona is charging for Ohtuvayre was added to the story.

作为慢性阻塞性肺病和哮喘的一线疗法，全球吸入制剂市场呈现一片欣欣向荣之景。从市场规模来看，2018-2023年全球吸入制剂销售额复合增长率为2.68%；2023年销售额同比增长6.17%，接近3500亿元。中国吸入制剂市场规模总体呈快速增长趋势，2018-2023年销售额复合增长率为7.62%；2023年销售额超过150亿元，约为全球规模的4%，预计未来市场规模仍将保持高速增长。面对国内吸入制剂百亿级蓝海市场，哪些国内药企正发起冲锋？01近3500亿市场，一条隐秘的蓝海赛道吸入制剂与普通口服制剂相比，其优势在于药物可直接进入肺部，起效迅速，避免了首过效应，降低给药剂量；与注射剂相比，经口吸入制剂可以提高患者的依从性，减少不良反应的发生率。因此，吸入疗法被慢性阻塞性肺疾病全球倡议（GOLD）、全球支气管哮喘防治倡议（GINA）和我国指南推荐为一线疗法。表1 吸入给药与口服、静脉给药的特性比较数据来源：《稳定期慢性气道疾病吸入装置规范应用中国专家共识（2019年）》吸入制剂是由药物处方和雾化装置组成的药械组合产品，按剂型/装置类型分为：吸入粉雾剂、吸入气雾剂、吸入雾化液体制剂、软雾剂。按药理作用机制分为：支气管扩张剂、糖皮质激素、复方制剂（支气管扩张剂和糖皮质激素）。表2 吸入制剂/装置的分类及特点数据来源：《吸入装置的分类、特点及注意事项》，长风药业公开招股书经调研，全球吸入制剂市场规模总体呈增长趋势，2018-2023年销售额复合增长率为2.68%；2023年销售额同比增长6.17%，接近3500亿元。中国吸入制剂市场规模总体呈快速增长趋势，2018-2023年销售额复合增长率为7.62%；2023年销售额同比增长7.69%，超过150亿元（约为全球规模的4%，预计未来市场规模仍将保持高速增长）。图1 全球吸入制剂市场规模，单位：亿元图2 中国吸入制剂市场规模，单位：亿元数据来源：药智数据的样本放大数据，药智咨询整理02全球吸入制剂竞争格局分析按剂型分经调研，全球吸入制剂销售额按剂型分，干粉吸入剂（吸入粉雾剂）市场份额约为47%，销售额占比稳定，其次为吸入气雾剂和吸入雾化液体制剂。中国市场则以吸入雾化液体制剂为主（60%-70%），干粉吸入剂市场份额约为30%。图3 全球各剂型吸入剂销售额占比，按人民币计图4 中国各剂型吸入剂销售额占比，按人民币计数据来源：药智数据，药智咨询整理按适应症分经调研，全球吸入制剂销售额按适应症分，呼吸系统用药几乎垄断，其中抗哮喘和COPD药市占率接近95%。其他适应症包括抗感染药（呼吸道）、肺动脉高压用药和诊断试验/影响用药等。中国吸入制剂中，呼吸系统用药几乎垄断，其中抗哮喘/COPD药和止咳祛痰感冒用药合计市占率超过90%，肺表面活性剂市占率为6%-7%。图5 全球各适应症吸入制剂销售额占比，按人民币计图6 中国各适应症吸入制剂销售额占比，按人民币计数据来源：药智数据,药智咨询整理按活性成分计经调研，全球吸入制剂销售额按活性成分计，布地奈德/福莫特罗市占比最高，糠酸氟替卡松/乌美溴铵/维兰特罗销售额排第二且增长迅猛，氟替卡松/沙美特罗下滑严重。中国吸入制剂中，布地奈德排名第一但销售额及占比下滑严重，乙酰半胱氨酸作为雾化用祛痰药近几年销售额及占比增长迅猛。在COPD和哮喘适应症中复方制剂表现出了优于单药治疗的症状改善能力，近年来FDA批准的吸入制剂新药也以复方产品为主；但我国目前仍以单方为主，未来复方吸入制剂市场规模有望逐步扩大。图7 全球各活性成分吸入制剂销售额占比，按人民币计图8 中国各活性成分吸入制剂销售额占比，按人民币计数据来源：药智数据,药智咨询整理按制剂厂家分吸入制剂作为复杂制剂，无论在成熟的海外市场还是在国内市场，布局的企业及已上市的药品均相对较少。经调研，全球吸入制剂头部三个厂家（GSK、ASTRAZENECA和BOEHRINGER INGEL）合计市占比超过65%；其次CHIESI凭借倍氯米松单复方吸入制剂等销售额及占比取得快速增长。中国吸入制剂中，进口产品占绝对主导但整体有所下滑，主要受ASTRAZENECA旗下吸入用布地奈德混悬液销售额大幅下滑影响。目前国内销售前三厂家依次为ASTRAZENECA、GSK和健康元，健康元、正大天晴、四川普锐特等一批国内企业正在向这一高端复杂制剂领域冲刺，逐步打破寡头垄断格局并寻求逐步实现国产替代。图9 全球各厂家吸入制剂销售额占比，按人民币计图10 中国各厂家吸入制剂销售额占比，按人民币计数据来源：药智数据,药智咨询整理03结语面对国内吸入制剂百亿级蓝海市场，健康元、正大天晴、四川普瑞特等一批国内企业正在向这一高端复杂制剂领域冲刺，逐步打破寡头垄断格局并寻求逐步实现国产替代。声明：本内容为作者独立观点，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 | 金银花转载开白 | 马老师 18996384680（同微信）如需定制医药咨询服务，请扫描下方二维码咨询！ 阅读原文，是受欢迎的文章哦