The global study evaluates whether adding the dual-action inhaled therapy ensifentrine (Ohtuvayre) to standard care reduces lung disease exacerbations.
RT’s Three Key Takeaways:
- Phase 3 Study Initiation: Merck has begun patient enrollment in the ENHANCE-3 clinical trial to evaluate Ohtuvayre (ensifentrine) for preventing flare-ups in adults with COPD receiving standard care.
- Global Trial Scope: The study will enroll approximately 2,136 participants across 28 countries to assess the annualized rate of moderate or severe exacerbations over 52 weeks as its primary outcome.
- Dual-Action Inhaled Therapy: Approved by the FDA in June 2024 for maintenance therapy, the drug acts as a selective dual inhibitor combining bronchodilation and non-corticosteroid anti-inflammatory effects in a single molecule.
Merck has launched ENHANCE-3, a Phase 3 randomized clinical trial assessing Ohtuvayre (ensifentrine) for the prevention of COPD exacerbations in adult patients receiving standard of care who have a history of flare-ups, according to the company.
Recruitment for the trial has started, and the first patients are currently enrolling in the US, the pharmaceutical maker stated.
“Many patients with COPD continue to experience persistent symptoms such as shortness of breath, despite current standard-of-care therapy. For these patients, exacerbations remain a major driver of disease progression and diminished quality of life,” said Dr Mahesh Patel, vice president, global clinical development, Merck Research Laboratories, in a news release. “The initiation of the Phase 3 ENHANCE-3 study marks an important step in our efforts to further strengthen the body of evidence supporting Ohtuvayre and its potential to address significant unmet needs in COPD care. We remain committed to advancing innovative research to help the millions of people impacted by this disease worldwide.”
ENHANCE-3 Study Design and Endpoints
The ENHANCE-3 trial is a randomized, double-blind, placebo-controlled study that plans to enroll approximately 2,136 patients across 28 countries worldwide, according to Merck.
Participants in the trial will be randomized 1:1 to receive either Ohtuvayre twice daily plus standard of care or a placebo plus standard of care. Standard of care is defined as long-acting muscarinic antagonists (LAMA), long-acting beta-agonists (LABA), and inhaled corticosteroids (ICS), or LAMA and LABA if ICS is not appropriate, according to the release.
The primary endpoint of the study is the annualized rate of adjudicated moderate or severe COPD exacerbations over 52 weeks, the company reported. Secondary endpoints include:
- Change from baseline in forced expiratory volume in one second (FEV1) area under the curve 0 to 4 hours post-dose (AUC0-4h) at week 12,
- Responder status on the St. George’s Respiratory Questionnaire (SGRQ) at week 24 to assess health-related quality of life,
- The annualized rate of adjudicated severe COPD exacerbations over 52 weeks, and
- Overall safety.
Key inclusion criteria require adults aged 40 to 80 years with a confirmed COPD diagnosis for at least 12 months, a current or former smoking history, stable use of the same standard of care for at least two months, and a documented history of at least one moderate or severe COPD exacerbation in the year prior to enrollment, according to trial criteria released by Merck.
Mechanism and Current Regulatory Status
Ohtuvayre is an inhaled selective dual inhibitor of phosphodiesterase 3 and 4 (PDE3 and PDE4). According to the company, it represents the first and only inhaled mechanism for COPD maintenance treatment in more than 20 years to unite bronchodilator activity and non-corticosteroid anti-inflammatory effects in a single molecule.
The drug was approved by the Food and Drug Administration (FDA) in June 2024 for the maintenance treatment of COPD in adult patients, Merck reported. That regulatory approval followed data from the Phase 3 ENHANCE-1 and ENHANCE-2 trials, where the medication met primary endpoints by producing statistically significant improvements in lung function alongside an established safety profile supporting maintenance use.
Beyond COPD, Ohtuvayre is also being investigated in a Phase 2 clinical study for the treatment of non-cystic fibrosis bronchiectasis, according to the manufacturer. Merck stated it plans to submit findings from the ENHANCE-3 trial to global healthcare regulatory authorities upon completion.
