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.


  1. Verona Pharma
  2. Dual inhibitor of PDE3 and PDE4
  3. Nebulized formulation administered twice daily for maintenance treatment of COPD
  4. Also being evaluated to treat asthma, cystic fibrosis and idiopathic pulmonary fibrosis
  5. ~28k diagnosed prevalent cases in the G7 markets in 2023

Why is it a drug to watch?

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:

  1. 36%-42% reduction in the rate and risk of COPD exacerbations over 24 weeks
  2. 87-94 mL placebo-corrected change from baseline in average FEV1 area under the curve 0 to 12 hours post dose at week 12
  3. Statistically (ENHANCE-1) or clinically (ENHANCE-1 and ENHANCE-2) significant improvements in quality of life
  4. Improvements were consistent across subgroups, including gender, age, smoking status, COPD severity, background medication, inhaled corticosteroids use, chronic bronchitis and geographic region

Review and
approval status

September 2023

  • NDA accepted: U.S. FDA

June 26, 2024

  • PDUFA date

How will ensifentrine impact the market for COPD?

  1. Maintenance therapies will be the primary growth driver of the COPD market.
  2. Although biologics will capture less than 1% of COPD patients, they could generate combined sales of more than $3.4 billion, contributing to nearly 14.2% of the COPD market in 2032.
  3. However, novel emerging therapies, such as ensifentrine, that address daily symptoms, minimize exacerbations and improve quality of life will likely contribute significantly to the COPD market toward the end of the forecast period (depending on approval).
  4. Ensifentrine is in the most advanced stage of development of all novel drugs including biologics, and it will most likely be used as an add-on to a long-acting bronchodilator therapy.

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.

expected sales in 2029

Drug Timeline &
Success Rates

– Source: Cortellis Competitive Intelligence, Drug Timeline & Success Rates Prediction current as of November 3, 2023

Drugs to Watch 2024

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