Merck, known as MSD outside the United States and Canada, has initiated ENHANCE-3, a phase 3 clinical trial evaluating Ohtuvayre (ensifentrine) for the prevention of Chronic Obstructive Pulmonary Disease (COPD) exacerbations in adults receiving standard-of-care treatment. Recruitment has commenced in the United States, with the first patients now being enrolled.

The randomised, double-blind, placebo-controlled study is expected to enrol approximately 2,136 patients across 28 countries. Participants will receive either Ohtuvayre twice daily alongside standard-of-care treatment or a placebo alongside standard-of-care treatment. Eligible patients will be adults aged 40–80 years with a confirmed COPD diagnosis and a history of at least one moderate or severe exacerbation in the preceding year.

The primary endpoint is the annualised rate of adjudicated moderate or severe COPD exacerbations over 52 weeks. Secondary endpoints include improvements in lung function, health-related quality of life, the rate of severe exacerbations and overall safety.

Commenting on the trial initiation, Dr. Mahesh Patel, Vice President, Global Clinical Development, Merck Research Laboratories, said that COPD patients continue to experience persistent symptoms, including breathlessness, despite existing standard treatments. He added that exacerbations remain a major contributor to disease progression and reduced quality of life. The ENHANCE-3 study is expected to strengthen the clinical evidence supporting Ohtuvayre and its potential role in addressing unmet needs in COPD care.

Ohtuvayre (ensifentrine) is a selective dual inhibitor of phosphodiesterase 3 and 4 (PDE3 and PDE4). It combines bronchodilator and non-corticosteroid anti-inflammatory effects in a single inhaled therapy. The US Food and Drug Administration (FDA) approved the drug in June 2024 for the maintenance treatment of COPD in adults, based on findings from the ENHANCE-1 and ENHANCE-2 phase 3 trials. The therapy demonstrated statistically significant and clinically meaningful improvements in lung function in both studies.

In addition to its COPD development programme, Ohtuvayre is being evaluated in a phase 2 clinical trial for non-cystic fibrosis bronchiectasis. Results from ENHANCE-3 are expected to be submitted to regulatory authorities globally.