Ensifentrine is an inhaled dual phosphodiesterase (PDE)3 and PDE4 inhibitor that is expected to reduce exacerbations in moderate to severe Chronic Obstructive Pulmonary Disease (COPD) without the systemic side effects of current PDE inhibitors that are delivered orally. If approved, it would be the first in class as well as the first novel mechanism that has become available for maintenance COPD treatment in more than 10 years. The clinical and safety profile of ensifentrine makes it a promising addition to the limited treatment class options available for this patient population.
Ensifentrine is a novel, potent and selective dual inhibitor of PDE3 and PDE4 that combines bronchodilator and nonsteroidal anti-inflammatory activities in one compound. It also promotes ciliary function, which could potentially improve sputum-associated symptoms. The FDA submission was based on positive results from two phase 3 trials (ENHANCE-1 and ENHANCE-2) that evaluated the efficacy and safety of nebulized ensifentrine as monotherapy or as an add-on to a long-acting muscarinic antagonist or long-acting beta-agonist in patients aged 40 years to 80 years with moderate to severe COPD. The findings showed the following:
June 26, 2024
How will ensifentrine impact the market for COPD?
What gaps in treatment does ensifentrine fill?
Individuals with COPD rely on inhaled maintenance therapies (e.g., bronchodilators and inhaled corticosteroids [ICS]) for long-term control of symptoms and exacerbations. However, limited treatment options remain available, and patients can experience unpleasant systemic effects. The dual inhibition of PDE3/4 following inhaled ensifentrine administration directly to the lungs maximizes local effects in the lung (bronchodilation and anti-inflammatory effects) and minimizes the possibility of the side effects experienced with orally delivered PDE inhibitors.
What hurdles might it need to overcome to reach blockbuster status?
Ensifentrine offers an incremental benefit and does not represent a transformative treatment paradigm, which could limit uptake. The initial release in only a nebulized form might also be seen as a disadvantage for some patients who prefer a more portable inhaler (dry powder or metered dose). Inhalers are smaller, and patients have already been exposed to them through other treatments. The need to learn how to use, clean and maintain a nebulizer plus the twice-daily administration at home could be a major hurdle. Therefore, in its nebulized form, ensifentrine might be limited to hospital-bound or the most elderly patients.
“Neutrophilic inflammation is the most dominant pathway in COPD and is often poorly responsive to steroids. Ensifentrine is a drug that is very effective against neutrophils as well, so that is a potentially important way of reducing the major inflammatory component of COPD.”
– Source: Cortellis Competitive Intelligence, Drug Timeline & Success Rates Prediction current as of November 3, 2023