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FDA Approves Novel Nebulized Therapy for COPD

— First-in-class dual phosphodiesterase inhibitor lands broad indication for COPD maintenance

by Elizabeth Short, Staff Writer, MedPage Today

MedpageToday
FDA APPROVED ensifentrine (Ohtuvayre) over a computer rendering of transparent lungs.

The FDA approved inhaled ensifentrine (Ohtuvayre) as maintenance treatment for chronic obstructive pulmonary disease (COPD) in adults, drugmaker Verona Pharma on Wednesday.

A first-in-class dual phosphodiesterase 3 (PDE3) and phosphodiesterase 4 (PDE4) inhibitor, the nebulized therapy acts as both a bronchodilator and non-steroidal anti-inflammatory, simultaneously relaxing airway muscles and reducing inflammation and mucus production.

Ensifentrine becomes the "first inhaled product with a novel mechanism of action available for the maintenance treatment of COPD in more than 20 years," according to the company.

Approval was supported by the phase III ENHANCE-1 and ENHANCE-2 trials, both of which demonstrated improvements in lung function and reduced exacerbation rates with ensifentrine compared with placebo.

For the primary outcome, twice-daily treatment with a 3-mg dose of the nebulized therapy resulted in significant improvements in forced expiratory volume in 1 second (FEV1). From baseline to week 12, average FEV1 area under the curve at 0 to 12 hours improved by 87 mL and 94 mL versus placebo (P<0.001 for both).

Treatment with ensifentrine also improved time to first exacerbations in both trials and at week 24, the drug reduced the rate of moderate or severe exacerbations by 36% and 43%. Ensifentrine also improved symptoms and quality of life in ENHANCE-1 at week 24, but not in ENHANCE-2.

"In my experience, despite maintenance therapy, most patients report grappling with daily symptoms, including breathlessness and persistent coughing," Michael Wells, MD, of the University of Alabama at Birmingham, said in a statement from the drugmaker.

"COPD has a significant impact on both mortality and morbidity in the U.S., and until today, innovation in inhaled treatment modalities has been limited to combinations of existing treatment classes for over two decades," he added. "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."

Treatment with ensifentrine was well-tolerated in the ENHANCE trials, with adverse event rates similar to placebo. According to the , the most common adverse events with ensifentrine in trials included back pain, high blood pressure, urinary tract infection, and diarrhea, all of which were reported in fewer than 2% of participants.

Ensifentrine is not to be used as a rescue medication for acute symptoms. Users are also warned to stop therapy if paradoxical bronchospasm occurs and that psychiatric events, including suicidality, have been reported with use. "Carefully weigh the risks and benefits of treatment with Ohtuvayre in patients with a history of depression and/or suicidal thoughts or behavior," the labeling states.

Ensifentrine exposure increases in patients with hepatic impairment and caution should be taken for this population.

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    Elizabeth Short is a staff writer for MedPage Today. She often covers pulmonology and allergy & immunology.