FDA Approves Ensifentrine for Maintenance Treatment of Adult Patients With COPD

The FDA has approved ensifentrine (Ohtuvayre; Verona Pharma) for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adult patients.¹

Ensifentrine is a dual phosphodiesterase (PDE)3 and PDE4 inhibitor delivered directly to the lungs through a standard jet nebulizer. The approval was based on findings from the phase 3 ENHANCE trials (NCT04535986), which included 2 replicate randomized, double-blind, placebo-controlled, multicenter trials (ENHANCE-1 [NCT04542057] and ENHANCE-2 [NCT04778397]). These trials analyzed the efficacy of nebulized ensifentrine on lung function, quality of life, symptoms, and exacerbations in patients with COPD.² The FDA accepted Verona Pharma’s new drug application filing for ensifentrine in August 2023.^2,3

This is the first inhaled product with a novel mechanism of action available for maintenance COPD treatment in over 20 years.¹ The researchers noted that their findings showed that ensifentrine is “…a valuable and complementary addition to the limited available treatment mechanisms for patients with COPD.”²

"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 and CEO of Verona Pharma. "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."¹

The FDA has approved ensifentrine (Ohtuvayre; Verona Pharma) for the maintenance treatment of moderate to severe chronic obstructive pulmonary disease based on successful phase 3 ENHANCE trials. | Image Credit: Olivier Le Moal - stock.adobe.com

The phase 3 ENHANCE trials analyzed patients with moderate to severe symptomatic COPD, who were aged 40 to 80 years, at 250 research centers across 17 countries from September 2020 to December 2022.² Consequently, 760 patients in the ENHANCE-1 trial and 789 patients in ENHANCE-2 were randomized and treated; of each study population, 69% and 55% received concomitant long-acting muscarinic antagonists, respectively.

Overall, ensifentrine significantly improved lung function across both trials. Versus placebo, ensifentrine significantly improved average forced expiratory volume in 1 second (FEV₁) area under the curve at 0 to 12 hours in both the ENHANCE-1 (87 mL; 95% CI, 55-119) and ENHANCE-2 (94 mL; 95% CI, 65-124) trials (both P < .001). Conversely, at week 24, ensifentrine significantly improved the quality of life and symptoms compared with placebo in the ENHANCE-1 study population but not in the ENHANCE-2 study population.

However, the researchers found that ensifentrine treatment reduced the rate of moderate or severe exacerbations over 24 weeks in ENHANCE-1 (rate ratio [RR], 0.64; 95% CI, 0.40-1.00; P = .050) and ENHANCE-2 (RR, 0.57; 95% CI, 0.38-0.87; P = .009) vs the placebo group; it also increased time to first exacerbation among the ENHANCE-1 (HR, 0.62; 95% CI, 0.39-0.97; P = .038) and ENHANCE-2 (HR, 0.58; 95% CI, 0.38-0.87; P = .009) populations.

Ensifentrine was well tolerated in both trials, with a similar proportion of adverse events reported in both treatment groups. In the ENHANCE-1 trial, 38.4% of patients taking Ensifentrine and 36.4% of patients taking placebo reported treatment-emergent adverse events (TEAEs). Similarly, in the ENHANCE-2 trial, the ensifentrine (35.3%) and placebo (35.4%) groups reported a similar amount of TEAEs.

"Ensifentrine significantly improved lung function in both trials, with results supporting exacerbation rate and risk reduction in a broad COPD population and in addition to other classes of maintenance therapies," the authors concluded.

References

1. Verona Pharma announces US FDA approval of Ohtuvayre (ensifentrine). News release. GlobeNewswire News Room. June 26, 2024. Accessed June 26, 2024. https://www.globenewswire.com/news-release/2024/06/26/2904839/0/en/Verona-Pharma-Announces-US-FDA-Approval-of-Ohtuvayre-ensifentrine.html

2. Anzueto A, Barjaktarevic IZ, Siler TM, et al. 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). Am J Respir Crit Care Med. 2023;208(4):406-416. doi:10.1164/rccm.202306-0944OC

3. Pipeline. Verona Pharma. Accessed June 25, 2024. https://www.veronapharma.com/our-science/pipeline/