Merck launches Phase 3 ENHANCE-3 trial of OHTUVAYRE (ensifentrine) to prevent COPD exacerbations
- Planned enrollment ≈2,136 patients across 28 countries.
- Primary endpoint is the annualized rate of adjudicated moderate or severe COPD exacerbations over 52 weeks.
- Patients randomized 1:1 to ensifentrine (OHTUVAYRE) twice daily plus standard of care or placebo plus standard of care; standard of care defined as LAMA/LABA±ICS.
- OHTUVAYRE is a dual PDE3/4 inhaled inhibitor and was approved by the FDA in June 2024 for COPD maintenance based on ENHANCE‑1 and ENHANCE‑2.
Trial initiation
Merck has initiated ENHANCE‑3 (NCT07874815), a Phase 3 randomized, double‑blind, placebo‑controlled study evaluating OHTUVAYRE (ensifentrine) for prevention of COPD exacerbations. Recruitment has begun and the first patients are enrolling in the United States.
Study design and endpoints
The trial plans to enroll approximately 2,136 patients in 28 countries. Participants will be randomized 1:1 to receive OHTUVAYRE twice daily plus standard of care (SOC) or placebo plus SOC. The primary endpoint is the annualized rate of adjudicated moderate or severe COPD exacerbations over 52 weeks. Secondary endpoints include change from baseline in FEV1 AUC0‑4h at week 12, SGRQ responder status at week 24, the annualized rate of adjudicated severe exacerbations over 52 weeks, and overall safety.
Eligibility
Key criteria include adults aged 40–80 with a confirmed COPD diagnosis for at least 12 months, current or former smoking history, use of the same SOC for at least two months, and at least one documented moderate or severe exacerbation in the prior year.
OHTUVAYRE background, safety and dosing
OHTUVAYRE is a first‑in‑class inhaled selective dual PDE3 and PDE4 inhibitor that combines bronchodilation and non‑corticosteroid anti‑inflammatory effects. It met primary endpoints in ENHANCE‑1 and ENHANCE‑2 and received FDA approval for COPD maintenance in June 2024; it is also under evaluation in Phase 2 for non‑cystic fibrosis bronchiectasis. Select safety points: contraindicated in patients with hypersensitivity to ensifentrine; not for relief of acute bronchospasm; possible paradoxical bronchospasm; psychiatric events including suicide‑related reactions were reported (1 suicide attempt, 1 suicide). Common adverse reactions ≥1% versus placebo included back pain, hypertension, urinary tract infection and diarrhea. Recommended dose is 3 mg (one unit‑dose ampule) twice daily via a standard jet nebulizer; ensifentrine exposure increases ~2.3‑fold in moderate/severe hepatic impairment.
Source: Merck