Merck has initiated a global Phase 3 clinical trial to evaluate Ohtuvayre (ensifentrine) for preventing exacerbations in adults with chronic obstructive pulmonary disease (COPD). The study, named ENHANCE-3 (NCT07874815), will assess the drug’s effectiveness when added to standard-of-care treatment in patients with a history of COPD exacerbations.
Patient enrolment has begun in the United States, marking another step in Merck’s efforts to expand clinical evidence supporting Ohtuvayre as a potential treatment option for COPD.
ENHANCE-3 Trial to Enrol Over 2,100 Patients
The randomised, double-blind, placebo-controlled Phase 3 trial plans to enrol approximately 2,136 patients across 28 countries. Participants will receive either Ohtuvayre twice daily alongside standard-of-care treatment or a placebo combined with standard therapy.
The study will run for 52 weeks and primarily evaluate the annualised rate of moderate or severe COPD exacerbations. Researchers will also assess changes in lung function, health-related quality of life, severe exacerbations and overall safety.
The trial will include adults aged 40 to 80 years who have a confirmed COPD diagnosis and a history of at least one moderate or severe exacerbation in the previous year. Participants must also have received the same standard-of-care treatment for at least two months before enrolment.
Ohtuvayre Combines Two Therapeutic Actions
Ohtuvayre (ensifentrine) is a first-in-class, 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 Ohtuvayre in June 2024 for the maintenance treatment of COPD in adults. It is the first novel inhaled mechanism introduced for COPD maintenance treatment in more than 20 years.
The drug demonstrated statistically significant and clinically meaningful improvements in lung function in the Phase 3 ENHANCE-1 and ENHANCE-2 studies. Merck is also evaluating ensifentrine in a Phase 2 clinical trial for non-cystic fibrosis bronchiectasis.
Merck Highlights Unmet Needs in COPD Treatment
Commenting on the trial initiation, Dr Mahesh Patel, Vice President, Global Clinical Development, Merck Research Laboratories, said many COPD patients continue to experience symptoms such as breathlessness despite receiving standard treatment.
He highlighted that exacerbations remain a major factor contributing to disease progression and reduced quality of life. According to Patel, ENHANCE-3 will help strengthen the clinical evidence supporting Ohtuvayre and assess its potential to address unmet needs in COPD management.
COPD Continues to Affect Millions Worldwide
COPD is a progressive respiratory disease that restricts airflow and makes breathing difficult. Its two most common forms are emphysema and chronic bronchitis.
Common symptoms include persistent coughing, wheezing, chest tightness, breathlessness and fatigue. These symptoms can interfere with everyday activities and may worsen during exacerbations. Smoking and air pollution remain among the leading causes of the disease.
An estimated 390 million people worldwide were living with COPD in 2019. Although the condition has no cure, appropriate treatment can help manage symptoms, improve lung function and reduce the risk of complications.
Merck, known as MSD outside the United States and Canada, continues to advance research in cardiometabolic and respiratory diseases, including COPD, heart failure, pulmonary hypertension and atherosclerotic cardiovascular disease. As reported by PharmaBiz (pharmabiz.com), Merck’s initiation of the ENHANCE-3 trial marks a further step in evaluating Ohtuvayre’s potential role in preventing COPD exacerbations and improving long-term disease management.