Verona Pharma Drug With Dual Mechanism Lands FDA Approval in COPD

Chronic obstructive pulmonary disease, or COPD, hasn’t seen any novel drugs in more than a decade. The FDA has approved a new inhalable medication whose innovation brings patients a dual approach to this common respiratory condition.

The Verona drug, ensifentrine, won its regulatory nod late Wednesday as a maintenance treatment for COPD. The approval comes with a broad label that permits use of the inhaled therapy as a standalone treatment or alongside other COPD medications. London-based Verona will market its new product under the brand name Ohtuvayre.

COPD leads to an obstructed airway and excess mucus production. Smoking is a risk factor for COPD, but nonsmokers can also develop the chronic condition. COPD patients often experience exacerbations, flare-ups that worsen symptoms such as coughing, wheezing, and breathing difficulty. The Centers for Disease Control and Prevention estimates that 16 million adults in the U.S. have COPD, one of the leading causes of death in the country.

The COPD drugs available include bronchodilators that open airways and anti-inflammatory medications that reduce swelling and mucus production. The last novel COPD drug was roflumilast, which won FDA approval in 2011. AstraZeneca now holds rights to Daliresp, which is starting to face generic competition. The nonsteroidal drug blocks the PDE-4 enzyme to stop inflammation. While Daliresp was welcomed as the first PDE-4 inhibitor for COPD, the once-daily pill had problems, Verona CEO David Zacchardelli said in an interview. Daliresp causes adverse effects in the gut, such as nausea and diarrhea. Those complications lead some patients to stop taking the drug.

“Its use is more limited because of its [adverse effect] profile,” Zaccardelli said. “It’s also not a bronchodilator. It may reduce the exacerbation rate, but it is not improving breathing. It did give us great insight that PDE-4 inhibition is a route for COPD.”

Verona’s Ohtuvayre combines two mechanisms of action in a single drug. In addition to blocking PDE-4 to counteract inflammation, the drug blocks PDE-3 enzymes. While PDE-3 inhibitors have been developed for heart failure, Verona leverages this mechanism to bring patients bronchodilation. The small molecule is formulated for twice-daily dosing via a nebulizer.

FDA approval of Ohtuvayre is based on two global, placebo-controlled Phase 3 studies that enrolled 1,549 COPD patients between the ages of 40 and 80. The main goal was to show lung function improvement according to a measure of how much air a patient can exhale in a specific amount of time. In addition to statistically significant improvement on that goal in both trials, the studies posted positive results on secondary goals that included other measures of respiratory function and quality of life. The most common adverse reactions were back pain, hypertension, urinary tract infection, and diarrhea. Discontinuation rates in the study drug were low, and comparable to placebo. The study results were published a year ago in the American Journal of Respiratory and Critical Care Medicine.

Of the approximately 8.6 million Americans receiving maintenance therapies for COPD, Verona estimates about half of them still have persistent symptoms. Dr. Mike Wells, a pulmonologist and associate professor at the University of Alabama, Birmingham, said on a Verona conference call Thursday that most of the COPD patients he sees still experience symptoms despite taking two or three therapies. While clinicians focus on reducing exacerbations and hospitalizations, patients focus on the impact to daily life, such as the ability to climb stairs without coughing, he said.

“The opportunity for Ohtuvayre in this setting is that we do know it improves lung function,” Wells said. “It is going to reduce symptoms. That is going to be massively impactful for patients.”

Verona plans to launch its new drug in the third quarter of this year. The company set a wholesale price of $2,950 per month for the product, or $35,400 per year. The drug price watchdog group the Institute for Clinical and Economic Review (ICER) calculated that Verona’s drug would be cost effective priced in the range of $7,500 and $12,700 per year. One of ICER’s concerns is uncertainty about how much patient benefit comes from Verona’s drug when used alongside existing therapies.

“Longer term and larger studies are needed to characterize the magnitude of the benefit of ensifentrine added on to dual and triple therapy, the patient population for whom the drug is most likely to be prescribed for in clinical practice,” ICER said in its report.

As of the end of the first quarter of this year, Verona reported a $255 million cash position. In anticipation of the regulatory decision, the company last month raised $650 million in non-dilutive financing. At the time, executives estimated this combined capital would be sufficient to fund operations beyond 2026. While Verona is focused on the U.S. commercialization of Ohtuvayre, its first product, development of the drug in other markets will be done through partners.

Ohtuvayre’s dual mechanism of action has potential applications in other respiratory disorders. The drug has reached mid-stage clinical development in asthma and cystic fibrosis. It’s also in Phase 2 testing for non-cystic fibrosis bronchiectasis, a respiratory disease that currently has no FDA-approved therapies.

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