After decades of waiting, late-stage therapies may penetrate the COPD market this year

Therapies for chronic obstructive pulmonary disease (COPD) have been in continual development for decades to reduce exacerbations and the symptom load of the disease.

Of the nine late-stage pipeline agents that are currently in development for COPD globally, Sanofi/Regeneron’s Dupixent and Verona’s ensifentrine are close contenders trying to gain approval and entry in the market this year after positive Phase III clinical trial data was presented to the US Food and Drug Administration (FDA).

According to leading data and analytics company GlobalData’s Sales and Forecast database, total sales for Dupixent are forecast to reach $21.4bn globally by 2029, and ensifentrine is forecast to have sales of $1.1bn globally by 2029.

COPD is a heterogeneous, progressive lung disease characterised by chronic symptoms, including dyspnea, cough, sputum production, and/or exacerbations.

According to the 2023 Global Initiative for Obstructive Lung Diseases (GOLD), COPD presents due to abnormalities of the airways or alveoli that cause persistent, often progressive, airflow obstruction.

COPD patients are segmented in groups now known as the new 2023 GOLD A-E depending on the severity of symptoms and exacerbations/hospitalisations, formerly GOLD A-D.

Treatment options for COPD patients involve the introduction of bronchodilators (beta-2 agonists or muscarinic antagonists, short- or long-acting) or inhaled corticosteroids (ICS), which are given as either a triple therapy with long-acting beta-2 agonists (LABAs) and long-acting muscarinic antagonists or alongside LABAs as part of an ICS/LABA fixed-dose combination regimen.

Additionally, phosphodiesterase inhibitors (PDE) can be administered to patients as an add-on therapy, and include aminophylline, theophylline, or AstraZeneca’s roflumilast.

These therapies are considered to be tolerable by patients. However, the progressive nature of COPD has created a need for additional maintenance therapy alongside the standard of care (SoC).

A current gap in the market is the absence of biologics for COPD. Dupixent, an interleukin-4 and interleukin-13 inhibitor, has the potential to address this gap.

Positive results were reported from two Phase III clinical trials of Dupixent, BOREAS and NOTUS, and the primary endpoint was met in both trials.

The trials show that Dupixent significantly reduced moderate or severe acute COPD exacerbations by 30% in the BOREAS trial and by 34% in the NOTUS trial over 52 weeks and improved lung function at 12 weeks that was sustained through 52 weeks, compared to placebo.

The positive results from both clinical trials led the FDA to accept Sanofi/Regeneron’s supplemental Biologics License Application as an add-on maintenance therapy and set an FDA decision date for 27 June 2024.

Key opinion leaders interviewed as part of GlobalData’s research noted that Dupixent’s two trial endpoints are positive, and adding it would be a surprise if there was a pushback in the FDA decision.

Ensifentrine, a first-in-class dual PDE3/4 inhibitor administered as a nebulised formulation, has also gained the FDA’s interest after two positive Phase III trials (ENHANCE-1 and ENHANCE-2).

Both trials met their primary endpoint when ensifentrine was taken as a monotherapy or alongside the SoC as a maintenance therapy.

The trial results demonstrate that ensifentrine improved lung function and reduced the rate of moderate to severe COPD exacerbations when compared to placebo.

The positive outcome of these results formed the basis for the new drug application to the FDA in August 2023, with the Prescription Drug User Fee Act date being set for 26 June 2024.

The current late-stage pipeline for COPD is one to watch, specifically the potential introduction of biologics to the market as maintenance or add-on therapies for patients.

If biologics are approved and launched and are shown to manage symptoms, decrease exacerbations, and reduce hospitalisation, this breakthrough may bridge the gap present in the SoC for treating COPD patients.