Chronic obstructive pulmonary disease (COPD) is a group of diseases that causes breathing difficulties in nearly 16 million Americans and more than 250 million people around the world. It is estimated that COPD, which includes emphysema and chronic bronchitis, causes the deaths of about 3 million people annually. In the United States, it is the third leading cause of death.
There are many risk factors associated with COPD and, according to the World Health Organization, the number of confirmed diagnoses of the disorder is climbing across the globe, particularly in areas of low and middle income. In the United States, the Centers for Disease Control and Prevention, along with the National Institutes of Health, released a national action plan as a road map to address what it considers one of the most urgent health concerns facing the nation. COPD causes a narrowing of the airways, which in turn causes breathing problems that is often accompanies by a persistent cough and chest infections.
While there is no cure for the disease, there are a number of drugs that have been approved to treat the illness. And with the growing number of cases, the drug market for COPD is expected to dramatically increase as well. According to research composed by GlobalData, the COPD market is expected to increase from $9.9 billion to about $14.1 billion by 2025. Some of that growth will be from popular COPD drugs already on the market, such as Advair, Symbicort, Spiriva, Breo Ellipta, Trelegy Ellipta and more, but also due to the growing number of potential treatments currently in the developmental pipelines of pharma companies. With November being COPD Awareness Month, BioSpace takes a look at some of these clinical candidates, as well as some recently approved drugs.
Duaklir – This COPD drug won approval for from the U.S. Food and Drug Administration this year. Circassia Pharma’s Duaklir won approval for the maintenance treatment of COPD in April. Duaklir is a fixed-dose combination treatment of the long-acting muscarinic antagonist (LAMA) aclidinium bromide and long-acting beta-agonist (LABA) formoterol fumarate.
Breztri Aerosphere – AstraZeneca’s Breztri Aerosphere, formerly known as PT0101, was rejected by the FDA in October despite the medication having hit its endpoints in the Phase III KRONOS trial. In its announcement, AstraZeneca did not share the FDA’s concerns but noted that it will work with the regulatory agency as it moves forward. It is likely that the company will seek to use additional Phase III results from the ETHOS trial, PT0101 demonstrated a statistically-significant reduction in the rate of moderate or severe exacerbations compared with dual-combination therapies Bevespi Aerosphere (glycopyrronium/formoterol fumarate) and PT009 (budesonide/formoterol fumarate).
Nucala – GlaxoSmithKline has been positioning its IL-5 inhibitor Nucala as a possible treatment for COPD, but last year, the FDA raised doubts over the drug’s efficacy for that indication. An FDA staff report raised concerns over the drug’s “failure to meet a statistical threshold for effectiveness in one of the clinical trials.” The FDA staff report pointed to another IL-5 inhibitor, AstraZeneca’s Fasenra, which failed in a Phase III trial as a treatment for patients with moderate to very severe COPD. Nucala was initially approved in 2015 by the FDA to treat patients age 12 years and older with severe asthma with an eosinophilic phenotype.
Yupelri – In November 2018, the FDA approved Mylan and Theravance’s Yupelri, the first nebulized bronchodilator approved for the treatment of COPD in the United States. Yupelri, a long-acting muscarinic antagonist, was approved for the maintenance treatment of COPD. The approval was supported by Phase III data that showed Yupelri demonstrated statistically significant and clinically meaningful improvements as compared to placebo in trough forced expiratory volume in one second.
慢性阻塞性肺疾病（ COPD ）是一组疾病，在全世界近1600万美国人和超过2.5亿人中引起呼吸困难。据估计，慢性阻塞性肺病，包括肺气肿和慢性支气管炎，每年造成约300万人死亡。在美国，这是第三主要原因。
虽然没有治愈这种疾病的方法，但是有一些药物已经被批准用于治疗这种疾病。随着病例数量的增加， COPD 的药物市场预计也将大幅增加。根据 GlobalData 的研究，到2025年， COPD 市场预计将从99亿美元增加到141亿美元左右。其中一些增长将来自已上市的流行 COPD 药物，如 Advair 、 Symbistort 、 Spiriva 、 Breo Ellipta 、 Trelegy Ellipta 等，但也是由于制药公司开发管线中潜在治疗药物的数量不断增加。11月是 COPD 意识月， BioSpace 公司对其中一些临床候选药物以及最近批准的一些药物进行了研究。
Duaklir –这款 COPD 药物今年获得了美国食品药品监督管理局（Food and Drug Administration）的批准。Circia Pharma 的 Duaklir 在4月份获得了 COPD 维持治疗的批准。Duaklir 是一种固定剂量联合治疗长效麝香拮抗剂（ LAMA ）溴化酰亚胺和长效受体激动剂（ LABA ）富马酸表雄酮。
Breztri Aerosphere ——阿斯利康（AstraZeneca）的 Breztri Aerosphere ，前身为 PT0101，尽管药物在三期 KRONOS 试验中达到了终点，但 FDA 在10月份拒绝了该药物。阿斯利康（AstraZeneca）在其声明中并不认同 FDA 的担忧，但指出它将与监管机构合作，因为它将继续前进。公司可能会寻求使用 ETHOS 试验的其他 III 期结果， PT0101显示与双联疗法 Bevespi Aerosphere （糖吡咯烷/富马酸表雄酮）和 PT009（布地奈德/富马酸表雄酮）相比，中度或严重恶化的发生率有统计学意义的降低。
Nucala-GlaxoSmithKline 一直将其 IL-5抑制剂 Nucala 定位为可能的 COPD 治疗药物，但去年， FDA 对该药的疗效提出质疑。FDA 的一份工作人员报告对该药“未能达到临床试验中有效性的统计门槛”提出了担忧。FDA 的工作人员报告指出另一种 IL-5抑制剂阿斯利康（AstraZeneca）的 Fasenna 在 III 期试验中未能成功用于治疗中重度 COPD 患者。Nucala 最初于2015年被 FDA 批准用于治疗有嗜酸性表型的严重哮喘患者，年龄为12岁及以上。
Yupelli ——2018年11月， FDA 批准迈兰（Mylan）和 Theravance 的 Yupelli ，第一个在美国批准用于治疗 COPD 的雾化支气管扩张剂。尤培里是一种长效的麝香拮抗剂，被批准用于 COPD 的维持治疗。第三阶段的数据支持了这一批准，该数据显示，与安慰剂相比， Yupelli 在一秒钟内的谷压呼气量有统计学意义和有临床意义的改善。