FDA Approves Ensifentrine (Ohtuvayre) for COPD

The US Food and Drug Administration (FDA) has approved ensifentrine (Ohtuvayre) for the treatment of patients with chronic obstructive pulmonary disease (COPD).¹

Ensifentrine, an inhaled nonsteroidal nebulizer therapy from Verona Pharma, is a dual inhibitor of the phosphodiesterase 3 and 4 (PDE3; PDE4) pathways. It is now the first treatment with a novel mechanism of action to be approved for COPD in the last decade.

In a statement accompanying the approval, Michael Wells, MD, associate professor in the division of pulmonary, allergy and critical care medicine at the University of Alabama Birmingham, stressed the importance of improving the effect of COPD maintenance therapy on daily symptoms including breathlessness and persistent cough.

"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 2 decades," Wells said in the statement. "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.”

Verona’s New Drug Application (NDA) for ensifentrine as a treatment of patients with COPD was supported by data from the phase 3, pivotal ENHANCE clinical trial program—a pair of randomized, double-blind, placebo-controlled trials including approximately 800 patients with moderate to severe, symptomatic COPD across North America and Europe.²

In ENHANCE-2, investigators led by Antonio Anzueto, MD, professor of medicine and section chief of pulmonary at South Texas Veterans Healthcare System, analyzed the efficacy and safety of 3 mg nebulized ensifentrine monotherapy or add-on therapy to bronchodilators (either long-acting beta agonists [LABA] or long-acting muscarinic antagonists [LAMA]) versus placebo.

Patients were administered treatment twice-daily over 24 weeks, toward a primary endpoint of improved lung function per forced expiratory volume over 1 second (FEV₁) under the curve (AUC) at 0 – 12 hours post-dose at 12 weeks. Anzueto and colleagues also sought secondary endpoints of peak and morning trough FEV₁, COPD symptoms and health-related quality of life per St. George’s Respiratory Questionnaire (SGRQ) and Evaluating Respiratory Symptoms (ER-S) scores, at 12 weeks, and COPD exacerbations at 24 weeks. Safety outcomes were additionally observed over the 24-week trial.

For the primary outcome, investigators observed a 94 mL change in mean FEV1 AUC at 0-12 hours post-dose among patients receiving ensifentrine through week 12 (P <.0001). The team also observed a mean peak FEV₁ of 146 mL at 0 – 4 hours post-dose (P < .0001) and a mean 49 mL increase in morning trough FEV₁ (P = .0017) among treated patients, each at week 12. Overall, patients receiving either monotherapy or add-on nebulized 3 mg ensifentrine reported a 42% reduction in COPD exacerbations versus placebo over 24 weeks (P = .0109).

Additionally, Anzueto and colleagues observed clinically-significant improvement in patient E-RS and SGRQ scores at week 24—indicating benefit in health-related quality of life with ensifentrine—and the drug’s safety profile was consistent to the placebo. The most common adverse events included pneumonia, gastrointestinal effects and cardiovascular events.

David Zaccardelli, PharmD, president and chief executive officer of Verona Pharma, shared the company's excitement to make the new COPD maintenance option more widely available in the latter half of 2024.

“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,” Zaccardelli said in the statement.¹ “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.”

References

1. ^{Verona Pharma. Verona Pharma Announces US FDA Approval of Ohtuvayre™ (ensifentrine). Press release. Published June 26, 2024. https://www.veronapharma.com/news/verona-pharma-announces-us-fda-approval-of-ohtuvayre-ensifentrine/}
2. ^{Kunzmann K. Ensifentrine Significantly Improves COPD Lung Function, Exacerbations. HCPLive. Published August 9, 2022. https://www.hcplive.com/view/ensifentrine-significantly-improves-copd-lung-function-exacerbations}