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Did you know that chronic obstructive pulmonary disease (COPD) is actually the third leading cause of death worldwide? According to the World Health Organization (WHO), the lung disease – which restricts airflow and causes breathing problems – led to 3.23 million deaths in 2019 alone. This highlights the critical need for more therapies to be approved for COPD, as well as for finding a treatment that could become a promising cure for COPD and ultimately reverse the progression of the disease.
COPD is primarily caused by long-term exposure to irritants that damage the lungs, with smoking and air pollution being the most common causes of the disease. COPD falls under two main categories: emphysema and chronic bronchitis. Emphysema typically occurs when the tiny air sacs – alveoli – in the lungs become severely damaged, while chronic bronchitis refers to a chronic cough and phlegm production due to inflammation in the airways.
As COPD progresses, people find it more difficult to carry out their normal daily activities because of the resulting breathlessness. The disease is considered irreversible, which means that current treatment largely focuses on the management of symptoms and preventing the progression of the disease.
The main ones are inhaled medicines that open and reduce swelling in the airways, called bronchodilators. During flare-ups, steroids are often also used to reduce inflammation, as well as antibiotics to treat infections. Additionally, oxygen is used for people who have had COPD for a long time or have severe COPD, and pulmonary rehabilitation can be used to strengthen the lungs. People with extremely severe forms of the disease can undergo surgery to remove damaged lung tissue.
Furthermore, there is also another relatively new medical device treatment for COPD, approved by the U.S. Food and Drug Administration (FDA) in 2018, that goes beyond the standard therapies mentioned: an endobronchial valve implantation. These valves are minimally invasive and are essentially small devices that are placed in the airways to treat conditions like COPD. The valves work by redirecting airflow away from damaged parts of the lung, allowing healthier areas to function better. They create a one-way flow, enabling trapped air to escape during exhalation, while preventing new air from entering the damaged areas during inhalation. This helps restore balanced airflow, improves lung function, and alleviates symptoms, allowing people with emphysema to take deeper breaths.
At this moment in time, there is no cure for the disease. But, after more than a decade with no new therapeutic advancements, interest in COPD seems to have grown in the last year, which can be evidenced by the recent regulatory approvals of Verona Pharma’s Ohtuvayre and Regeneron and Sanofi’s blockbuster drug Dupixent. This ultimately offers hope that a promising cure for COPD may also soon be found.
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FDA approves two new COPD treatments in 2024
Verona Pharma’s Ohtuvayre
In June 2024, the FDA approved the first inhaled product with a novel mechanism of action available for the maintenance treatment of COPD in more than 20 years. The product, called Ohtuvayre (ensifentrine), was developed by Verona Pharma – a London-based company established 19 years ago to unlock the potential of ensifentrine. After undergoing nearly 20 clinical trials in COPD, the compound’s approval marked a significant milestone for Verona as its first commercial product.
Ohtuvayre is a selective dual inhibitor of the phosphodiesterase 3 (PDE3) and phosphodiesterase 4 (PDE4) enzymes, combining two properties in one medicine, which ultimately sets it apart in COPD for its ability to both open the airways of patients and reduce inflammation.
The drug’s approval was based on two phase 3 trials, which both met their primary endpoints by showing that Ohtuvayre improved lung function. Furthermore, a pooled analysis of the two studies showed that Ohtuvayre reduced flare-ups through 24 weeks by 40% in patients with moderate to severe COPD.
Ohtuvayre has a list price of $2,950 for a monthly supply, and GlobalData estimates that sales will reach $1.05 billion by 2029.
Dupixent COPD approval
And, just last month, there was another big win for COPD patients, as Regeneron and Sanofi announced that the FDA had expanded the label of their drug Dupixent – which is already approved in more than 60 countries to treat several conditions, including atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, prurigo nodularis, and chronic spontaneous urticaria – to treat COPD. This makes the drug the first biological treatment for patients with COPD in the U.S.
Dupixent is a fully human monoclonal antibody that inhibits the signaling of the IL4 and IL13 pathways, but it is not an immunosuppressant. The Dupixent development program has shown significant clinical benefit and a decrease in type 2 inflammation in phase 3 studies, establishing that IL4 and IL13 are two of the key and central drivers of type 2 inflammation that play a major role in multiple related and often co-morbid diseases.
Following recent approvals in the European Union (EU) and China, Duxipent’s U.S. approval is based on two phase 3 studies that showed the drug achieved significant reduction in COPD exacerbations, and also showed improvements in lung function and health-related quality of life compared to placebo.
According to Fierce Pharma, analysts at Evercore ISI have projected that a label expansion for COPD would add $3.5 billion in peak sales for Dupixent worldwide, basing their figure on a 30% uptake of the treatment for those who are eligible. The addition would put Dupixent’s sales potential at $20 billion by the end of this decade, which would make it one of the highest-selling drugs of all time.
Both of these recent drug approvals are an important recognition of the unmet need in COPD and the high-number patient population that a differentiated treatment could serve.
Transplanting patients’ own lung cells: A potential cure for COPD?
Although the approvals of Ohtuvayre and Duxipent signify great news for COPD patients, they are not cures for the disease.
In order to find an actual cure, researchers have been investigating stem cells, which are capable of differentiating into any cell in the body, as well as progenitor cells, which are descendants of stem cells and can only differentiate into the cells that belong to the same tissue or organ and are normally used by the body to repair and replace damaged tissue.
The results of this type of research have been conflicting, especially for stem cells. That is, until recently.
In September, delegates at the European Respiratory Society’s International Congress were told that, for the first time, researchers have shown it is possible to repair damaged lung tissue in patients with COPD using the patients’ own lung cells.
The research team included Professor Wei Zuo, of the School of Medicine, Tongji University, Shanghai, China, and chief scientist at Regend Therapeutics Ltd in China, as well as his colleagues, who were investigating whether a type of cell called P63+ lung progenitor cells might be able to regenerate lung tissue damaged by COPD.
“Stem cell and progenitor cell-based regenerative medicine may be the biggest, if not the only, hope to cure COPD,” Zuo told the congress. “P63+ progenitor cells are known for their ability to regenerate the tissues of the airways, and previously, we and other scientists have shown in animal experiments that they can repair the damaged epithelial tissue in the alveoli – the tiny air sacs in the lungs that play a crucial role in the exchange of gases between air breathed in and the blood supply to the lungs.”
This research was part of a phase 1 clinical trial. Here, the researchers set out to investigate the efficacy and safety of taking P63+ progenitor cells from the lungs of 20 COPD patients, using them to grow millions more in the laboratory, before transplanting them back into the patients’ lungs.
“In our trial, 35% of the patients had severe COPD and 53% had extremely severe COPD,” said Zuo. “Usually, many patients with such severe COPD will die quite quickly if their disease progresses. We used a tiny catheter that contains a brush to collect the progenitor cells from the patients’ own airways. We cloned the cells to create up to a thousand million more, and then we transplanted them back into the patients’ lungs via bronchoscopy in order to repair the damaged lung tissue.
“We found that P63+ progenitor cell transplantation not only improved the lung function of patients with COPD, but also relieved their symptoms, such as shortness of breath, loss of exercise ability, and persistent coughing. This means that the patients could live a better life, and usually with longer life expectancy.”
Looking ahead, the researchers are now planning a phase 2 trial of the treatment, which will evaluate its efficacy in a larger group of patients. The trial has been approved by China’s National Medical Products Administration (NMPA), the Chinese equivalent of the U.S. Food and Drugs Administration (FDA).
A promising future for COPD treatment
Although COPD does not yet have a cure and there was a long lull in therapeutic advancements until recently, the future now looks promising when it comes to treatment options for the disease. Because COPD is a leading cause of death worldwide, it means that there is now a significant focus on it, with a lot of resources and effort concentrated on finding innovative, effective treatments for the disease.
So much so that companies are rushing to the space with their experimental COPD medicines. GSK recently announced that its respiratory drug Nucala, alongside an inhaled maintenance therapy, lowered the rate of moderate or severe exacerbations among COPD patients for up to two years. Amgen and AstraZeneca’s asthma drug Tezspire is also in contention as a potential treatment for COPD, as it has shown promise in treating patients with a high blood eosinophil count (BEC). Plus, Regeneron and Sanofi have a second COPD candidate – an IL-33 inhibitor called itepekimab – being tested in two phase 3 trials.
Furthermore, the global COPD treatment market size is expected to hit around $29.88 billion by 2032, growing at a compound annual growth rate (CAGR) of 5.14% during the forecast period from 2023 to 2032. The main driver behind the rapidly growing market size is that the prevalence of COPD continues to increase worldwide, particularly in developing countries where smoking rates are high and air pollution is a significant problem.
Ultimately, the recent approvals of Ohtuvayre and Dupixent – as well as the promise of the treatments currently in development – mean that the quality of life and overall health of people living with COPD are constantly being improved. And, with more research being invested in regenerative medicine, a promising cure for COPD may well be on the horizon, too.
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