Verona Pharma recently presented six analyses from its Phase 3 ENHANCE studies of Ohtuvayre (ensifentrine) at the CHEST 2024 Annual Meeting, reinforcing the drug's efficacy across various chronic obstructive pulmonary disease (COPD) patient subgroups. The data indicate that ensifentrine, a first-in-class selective dual inhibitor of PDE3 and PDE4, improves lung function, reduces exacerbation rates, and enhances quality of life, irrespective of COPD severity, smoking status, or chronic bronchitis history.
The ENHANCE-1 and ENHANCE-2 trials, which enrolled over 1,500 adults with moderate to severe COPD, formed the basis for these analyses. Participants received either Ohtuvayre (3 mg) or a placebo twice daily via nebulizer over six months, in addition to their existing inhaled therapies. The primary endpoint in both trials was the change from baseline in forced expiratory volume in one second (FEV1). The results consistently demonstrated statistically significant and clinically meaningful improvements in lung function with Ohtuvayre treatment.
Impact Across COPD Severity
One oral presentation by Jessica Bon, MD, from Wake Forest University School of Medicine, focused on the impact of ensifentrine across different COPD severities. The analysis revealed that Ohtuvayre significantly improved lung function after three months, regardless of whether patients had moderate or severe airflow obstruction. Furthermore, the therapy improved COPD symptoms, including dyspnea, and enhanced overall quality of life in both severity groups. According to Dr. Bon, "Ensifentrine provides a novel mechanism of action for clinically meaningful improvements in lung function, symptoms, and quality of life regardless of COPD severity."
Benefits for Smokers and Former Smokers
Another presentation by Amy Dixon, PharmD, from Verona Pharma, highlighted the benefits of ensifentrine for both current and former smokers with COPD. The data showed significant improvements in lung function after three months in both groups. Additionally, Ohtuvayre reduced the risk of moderate or severe exacerbations by 43% in current smokers and 40% in former smokers compared to placebo.
Effects on Patients with Chronic Bronchitis
Jill Ohar, MD, from Wake Forest University School of Medicine, presented a poster on Ohtuvayre's effects on COPD patients with and without chronic bronchitis. The results indicated that ensifentrine was superior to placebo in alleviating COPD symptoms, including dyspnea, regardless of bronchitis history. The treatment also showed a trend toward greater life quality gains in both groups.
Healthcare Resource Utilization
Emily Wan, MD, from Brigham and Women’s Hospital and Harvard Medical School, presented data showing that ensifentrine reduced COPD-related healthcare resource utilization over 48 weeks.
Mechanism of Action
Ohtuvayre (ensifentrine) is a first-in-class, inhaled, dual inhibitor of phosphodiesterase 3 and 4 (PDE3 and PDE4). It uniquely combines bronchodilator and non-steroidal anti-inflammatory activities in one molecule. By inhibiting PDE3 and PDE4, ensifentrine leads to airway smooth muscle relaxation (bronchodilation) and reduction in inflammation, both key components in managing COPD.
William Stringer, MD, FCCP, Professor of Medicine at the David Geffen School of Medicine at UCLA, commented, "Ensifentrine is a remarkable addition to COPD therapy. It has the capacity to bronchodilate, reduce inflammation, augment mucociliary clearance, and reduce exacerbations in smokers and former smokers."
These analyses from the ENHANCE studies provide compelling evidence for the broad applicability of Ohtuvayre in managing COPD, addressing key unmet needs in this patient population.
