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..

大卫·杰克爵士去世13年后，他仍然是医疗保健领域的一支创新力量。周三，当FDA批准维罗纳制药公司（Verona Pharma）的Ohtuvayre（ensifentrine）治疗慢性阻塞性肺疾病（COPD）时，它提醒人们杰克在治疗呼吸系统疾病方面的非凡才能。。

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.

这位100年前出生的药理学家在40年前担任葛兰素史克公司研发负责人时发现了安芬特林。该化合物当时被称为RPL554，在杰克于1987年退休后，一直在努力取得成功。

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.

维罗纳（Verona）成立十九年来，为了释放恩西芬特林（ensifentrine）的潜力，RPL554在COPD中进行了近20次临床试验，维罗纳（Verona）最终将Ohtuvayre推向了终点，成为这家总部位于伦敦的公司的首个商业产品。

Ohtuvayre becomes the first novel treatment advance in more than a decade for COPD, an inflammatory condition which restricts airflow from the lungs and leaves patients struggling to breathe. Ohtuvayre is approved as an add-on medicine with current therapies.

Ohtuvayre成为十多年来COPD的第一个新的治疗进展，COPD是一种限制肺部气流并使患者难以呼吸的炎症性疾病。Ohtuvayre被批准为当前疗法的附加药物。

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.

作为磷酸二酯酶3（PDE3）和磷酸二酯酶4（PDE4）酶的选择性双重抑制剂，Ohtuvayre在一种药物中结合了两种特性，在COPD中具有开放患者气道和减轻炎症的能力。

“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.”

维罗纳首席执行官大卫·扎卡德利（DavidZaccardelli）在接受威猛制药（Fierce Pharma）采访时表示：“这确实是20多年来COPD吸入治疗的第一个新机制。”。“我们相信它的支气管扩张剂和非甾体抗炎活性有可能改变治疗模式。”

Doctors can prescribe Ohtuvayre as a monotherapy or as an add-on to an existing COPD maintenance treatment regimen. It is administered twice daily by a jet nebulizer, with sessions lasting between five minutes and seven minutes. Verona Chief Commercial Officer Chris Martin said that the company doesn’t expect the administration method to affect uptake much as roughly half of COPD patients already use hand-held devices..

医生可以将Ohtuvayre作为单一疗法或作为现有COPD维持治疗方案的补充。它由喷射雾化器每天两次给药，持续时间为5分钟至7分钟。维罗纳首席商务官克里斯·马丁（ChrisMartin）表示，该公司预计这种给药方法不会影响患者的摄取，因为大约一半的COPD患者已经使用了手持设备。。

“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.”  .

Martin说：“一些患者将其用于长期维护，许多患者将其用于抢救。这些患者使用雾化器非常舒适。”。“不幸的是，对于这些患者中的许多人来说，他们的[身体]活动水平远低于你或我的，因此雾化对他们的[日常]活动并不是一个大负担。”。

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 (LABA) and long-acting muscarinic agonists (LAMA). Some COPD patients are on a regimen with all three treatments.

通常用于控制COPD的疗法是吸入皮质类固醇，可以减轻炎症，支气管扩张剂可以放松肺部肌肉并拓宽气道。支气管扩张剂包括长效β受体激动剂（LABA）和长效毒蕈碱激动剂（LAMA）。一些COPD患者正在接受三种治疗方案。

Others, who can’t take corticosteroids, use a LAMA and LABA mix..

其他不能服用皮质类固醇的人则使用喇嘛和拉巴的混合物。。

“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.”

马丁说：“这项研究中真正令人兴奋的一点是，患者有时对类固醇有点紧张。”。“这种非甾体支气管扩张剂，非甾体抗炎药对他们非常有吸引力。”

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.

两项临床试验表明，Ohtuvayre单独或与当前的维持疗法一起表现良好。该药物对使用喇嘛和拉巴组合后仍有症状的患者最有效。

The phase 3 ENHANCE-I and ENHANCE-II trials met their primary endpoint 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.

通过显示Ohtuvayre改善了肺功能，3期ENSIGNE-I和ENSIGNE-II试验达到了主要终点。对这两项研究的汇总分析还表明，Ohtuvayre在24周内将中度至重度COPD患者的发作减少了40%。

Verona has yet to reveal a price for Ohtuvayre. The Institute for Clinical Economic Review (ICER), which assesses the value of pharmaceutical products, has estimated (PDF) that it would meet commonly used cost-effectiveness thresholds at an annual price between $7,500 and $12,700 per year.

维罗纳尚未透露Ohtuvayre的价格。评估药品价值的临床经济审查研究所（ICER）估计，它将达到常用的成本效益阈值，年价格在7500美元至12700美元之间。

“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..

ICER首席医疗官大卫·林德（DavidRind）在一份新闻稿中表示：“目前的证据表明，当与目前的一些吸入疗法联合使用时，安芬太尼可以减轻病情恶化，并且患者耐受性良好，但对于未经研究的吸入疗法组合，它可能会增加多少益处尚不确定。”。。

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Verona's ensifentrine will be a 'paradigm shift in COPD treatment,' GlobalData says

GlobalData说，维罗纳的恩西芬太尼将成为“COPD治疗的范式转变”

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..

维罗纳计划在今年第三季度推出Ohtuvayre。这一日期意义重大，因为预计Regeneron和赛诺菲将获得备受期待的Dupixent治疗COPD的批准，FDA的目标决定日期推迟到9月27日。这两家公司原本预计6月27日会有判决，但由于监管机构要求获得两项试验的额外数据，这两项试验已使Dupixent获得批准，因此被推迟了三个月。。

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 mega-blockbuster, bringing its peak sales potential to $20 billion.

三个月前，Evercore ISI的分析师预测，COPD的批准将为Regeneron和赛诺菲的超级大片带来每年35亿美元的潜在销售额增长，使其峰值销售潜力达到200亿美元。

As for Ohtuvayre, analysts see it achieving blockbuster status quickly, with GlobalData estimating sales to reach $1.05 billion by 2029.

至于Ohtuvayre，分析师预计它将很快取得大片地位，GlobalData预计到2029年销售额将达到10.5亿美元。

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.

这是对适应症中未满足的需求以及差异化治疗可以服务的大量人群的认识。在美国，860万患者接受了COPD慢性症状的治疗。全世界有超过3.9亿人患有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.”.

马丁说：“我们认为恩司芬太尼的适应症很广。它允许医生在860万个光谱中使用它。”。“我们在研究中听到的是，医生正在为持续有症状的患者寻找新的治疗选择。我们在各种不同的研究中看到，今天接受治疗的患者中至少有一半仍然持续有症状，并且对目前的治疗不满意。”。