FDA Approves Verona’s Ohtuvayre for the Maintenance Treatment of Chronic Obstructive Pulmonary Disease

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The FDA has approved Verona Pharma’s Ohtuvayre (ensifentrine) for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adult patients. Classified as a first-in-class selective dual inhibitor of phosphodiesterase 3 and 4 (PDE3 and PDE4), the treatment combines bronchodilator and non-steroidal anti-inflammatory effects in one molecule. According to the company, this marks the first time in 20 years that an inhaled product with a novel mechanism of action has been approved for COPD maintenance.¹

“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,” said David Zaccardelli, PharmD, president, CEO, Verona Pharma, in a press release. “We plan to launch Ohtuvayre in the third quarter 2024, ensuring Ohtuvayre is available to help the millions of patients who still experience daily COPD symptoms.”

Approval for Ohtuvayre was based on results from the multicenter, randomized, double-blind, parallel-group, placebo-controlled Phase III ENHANCE trials, conducted across 17 countries with 1,549 patients. Additionally, the trial aimed to evaluate the efficacy of Ohtuvayre compared with placebo for lung function, symptoms, quality of life, and exacerbations in patients with COPD. The primary endpoint of the trials was improvement from baseline in week 12 average FEV1 AUC0–12 h versus placebo, while the secondary endpoint was week 24 average daily rescue medication use over seven days.^1,2

Participants were divided into two groups ((ENHANCE-1 and ENHANCE-2). In the EHNANCE-1 group, 69% of patients received concomitant long-acting muscarinic antagonists or long-acting β2-agonists, with 55% of patients in the ENHANCE-2 group receiving the same. Post-bronchodilator FEV1 percentage predicted values were at 52% and 51%, respectively.

In ENHACE-1, patients were randomly assigned and treated over 24 weeks with either Ohtuvayre or a placebo, with a subgroup continuing treatment for up to 48 weeks. A total of 84.5% of this group completed the trial, with treatment withdrawal over 24 and 48 weeks being reported at 20.8% for Ohtuvayre-treated patients and 18.0% for placebo-treated patients, and 26.3% and 24.7%, respectively, in the 48-week subset.

For ENHANCE-2, which also took place over a 24-week period, 77.3% of randomly assigned patients completed the trial. In this group, treatment withdrawal occurred in 24.3% of Ohtuvayre-treated patients and 32.6% of placebo-treated patients.

Results found that Ohtuvayre was well tolerated in both trials, with an equal number of patients reporting adverse events (AEs). Treatment-emergent AEs were reported in 38.4% of Ohtuvayre patients and 36.4% of placebo patients, with withdrawal occurring in 6.1% and 6.4%, respectively. Reported AEs included nasopharyngitis, hypertension, back pain, toothache, pneumonia, urinary tract infections, diarrhea, sinusitis, and COVID-19.²

“In my experience, despite maintenance therapy, most patients report grappling with daily symptoms, including breathlessness and persistent coughing,” said Michael Wells, MD, associate professor, division of pulmonary, allergy, and critical care medicines, University of Alabama Birmingham, in the press release. “COPD has a significant impact on both mortality and morbidity in the US, and until today, innovation in inhaled treatment modalities has been limited to combinations of existing treatment classes for over two decades. 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.”

Ohtuvayre is expected to be fully available in the third quarter 2024 through a network of exclusive accredited specialty pharmacies, with Verona stating that they are fully prepared for the launch.¹

References

1. Verona Pharma Announces US FDA Approval of Ohtuvayre™ (ensifentrine). Verona Pharma. June 26, 2024. Accessed June 28, 2024. https://www.veronapharma.com/news/verona-pharma-announces-us-fda-approval-of-ohtuvayre-ensifentrine/

2. Ensifentrine, a Novel Phosphodiesterase 3 and 4 Inhibitor for the Treatment of Chronic Obstructive Pulmonary Disease: Randomized, Double-Blind, Placebo-controlled, Multicenter Phase III Trials (the ENHANCE Trials). American Journal of Respiratory and Critical Care Medicine. June 1, 2023. Accessed June 28, 2024. https://www.atsjournals.org/doi/10.1164/rccm.202306-0944OC