Verona Pharma has secured FDA approval for Ohtuvayre (ensifentrine) for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adult patients. This approval introduces the first inhaled COPD treatment with a novel mechanism of action in more than 20 years, offering new hope for millions struggling with this chronic condition. Ohtuvayre functions as a selective dual inhibitor of phosphodiesterase 3 (PDE3) and phosphodiesterase 4 (PDE4) enzymes, delivering both bronchodilator and non-steroidal anti-inflammatory benefits directly to the lungs via a standard jet nebulizer.
Novel Mechanism and Clinical Impact
Ohtuvayre's unique mechanism of action sets it apart in the COPD treatment landscape. By inhibiting both PDE3 and PDE4, the drug addresses two critical pathways involved in COPD pathology: airway obstruction and inflammation. This dual-action approach has demonstrated significant clinical benefits, as evidenced by the Phase III ENHANCE-1 and ENHANCE-2 trials published in the American Journal of Respiratory and Critical Care Medicine. These trials revealed improvements of 87 mL and 94 mL in forced expiratory volume (FEV1), a key measure of lung function, and a reduction in the frequency of moderate to severe COPD exacerbations.
David Zaccardelli, CEO of Verona Pharma, emphasized the potential of Ohtuvayre to transform COPD care, stating, "The approval of Ohtuvayre is a significant advance in COPD care, and we believe Ohtuvayre’s novel profile can change the treatment paradigm for COPD."
Clinical Trial Data
The FDA's approval was heavily influenced by the robust data from the ENHANCE trials. These studies not only showed statistically significant improvements in lung function but also demonstrated that Ohtuvayre was well-tolerated across a broad spectrum of patients with moderate to severe COPD. The trials included patients already on existing maintenance therapies, highlighting Ohtuvayre's potential as both a standalone and add-on treatment option. Specifically, the trials reported a statistically significant increase in FEV1 compared to placebo, with p-values < 0.0001 in both ENHANCE-1 and ENHANCE-2. Furthermore, the time to first moderate or severe exacerbation was significantly longer in the Ohtuvayre group compared to the placebo group (HR = 0.75, 95% CI: 0.60-0.93).
Market Launch and Financial Backing
Verona Pharma is gearing up to launch Ohtuvayre in the third quarter of 2024. The company has established a comprehensive launch strategy, including a fully staffed team and a network of accredited specialty pharmacies. To support this launch, Verona has secured approximately $1 billion in funding, including a $400 million debt financing agreement with Oxford Finance and Hercules Capital and an additional $650 million from Oaktree Capital Management and OMERS Life Sciences.
While the pricing for Ohtuvayre has not been officially announced, an analysis by the Institute for Clinical and Economic Review (ICER) suggested a cost-effective price range of $7,500 to $12,700 annually.
Expert Commentary
Michael Wells, MD, Associate Professor at the University of Alabama Birmingham, noted the importance of this new treatment option: "In my experience, despite maintenance therapy, most patients report grappling with daily symptoms, including breathlessness and persistent coughing... Ohtuvayre, as a first-in-class PDE3 and PDE4 inhibitor, offers a needed, unique approach and is an important advance in the treatment of COPD."
Broader COPD Landscape
COPD affects over 390 million people worldwide and remains a leading cause of death globally. The current treatment landscape primarily involves bronchodilators and inhaled corticosteroids, often in combination. Ohtuvayre's novel mechanism offers a new avenue for managing this debilitating disease. The COPD treatment market is also anticipating potential approval of Sanofi and Regeneron’s Dupixent (dupilumab), with an extended FDA decision deadline set for September 27, 2024.
