The U.S. Food and Drug Administration (FDA) has agreed to review Verona Pharma’s application seeking approval of inhaled ensifentrine as a maintenance treatment for chronic obstructive pulmonary disease (COPD).

FDA’s review team now has up to 10 months to examine all data filed with the new drug application and make a decision on whether or not to approve ensifentrine. The decision is due by June 26, 2024. If the therapy gets approved, Verona expects to launch it in the second half of next year, according to a recent company presentation.

“We are excited to work with the FDA as they review our new drug application for ensifentrine for the maintenance treatment of COPD,” David Zaccardelli, Verona’s president and CEO, said in an emailed statement to COPD News Today.

Zaccardelli called FDA’s acceptance “an important milestone towards our goal of bringing this potential first-in-class therapy to patients suffering with COPD.”

Recommended Reading

An illustration showing the words

COPD is a lung condition where the airways become narrowed and inflamed, making it hard to breathe. Its symptoms include shortness of breath, coughing, and wheezing, which can worsen over time. Available treatments can ease symptoms and slow progression.

“Ensifentrine, if approved, is expected to be the first novel mechanism available for the maintenance treatment of COPD in more than 10 years,” Zaccardelli said in a company press release.

Ensifentrine works by blocking the action of two lung enzymes, called phosphodiesterase 3 and phosphodiesterase 4, that are involved in muscle contraction and airway inflammation, and mucus production and clearance.

Ensifentrine works in three ways

Therefore, ensifentrine works in three ways: as a bronchodilator that widens the airways to make breathing easier; as an anti-inflammatory agent; and as a clearing agent that helps sweep mucus and trapped particles off the airways to keep them clean.

“We believe ensifentrine, with its novel bronchodilator and non-steroidal anti-inflammatory activity, could change the treatment paradigm for COPD patients,” Zaccardelli said in the email.

Verona’s application was supported by data from two Phase 3 clinical trials: ENHANCE-1 (NCT04535986) and ENHANCE-2 (NCT04542057). In these studies, ensifentrine, used alone or as an add-on to a bronchodilator, was tested against a placebo in more than 1,500 adults with moderate to severe COPD.

The primary objective of both trials was to assess changes in forced expiratory volume in 1 second (FEV1), a measure of lung function, after 12 weeks, or about three months. Average FEV1 was calculated over 12 hours after one dose.

We believe ensifentrine, with its novel bronchodilator and non-steroidal anti-inflammatory activity, could change the treatment paradigm for COPD patients.

Patients on ensifentrine had significant improvements in FEV1

Patients on ensifentrine had significant improvements in FEV1 compared with those on a placebo: by 87 mL in ENHANCE-1 and by 94 mL in ENHANCE-2.

Secondary measures included exacerbations, health-related quality of life, and side effects. Exacerbations were defined as a worsening of symptoms requiring at least three days of treatment with steroids and/or antibiotics, or hospitalization.

Pooled data from both trials showed ensifentrine significantly reduced the rate of exacerbations by 40% compared with a placebo. There was also a 41% risk reduction in time to a first exacerbation.

Ensifentrine was significantly better than a placebo at reducing daily symptoms in ENHANCE-1, being associated with clinically meaningful score differences in the Evaluating Respiratory Symptoms scale after three and six months of treatment.

While clinically meaningful reductions in daily symptoms in ENHANCE-2 were observed in ensifentrine-treated patients also at three and six months, differences versus a placebo reached statistical significance only at three months.

Notably, shortness of breath — the “most debilitating symptom impacting patients with COPD,” Verona stated — was reduced significantly at all time points in both trials.

Recommended Reading

Main banner for Caroline Gainer's column,

Improvement in health-related quality of life in ensifentrine group

Health-related quality of life was assessed using the St. George’s Respiratory Questionnaire (SGRQ). There was an “early and sustained improvement in SGRQ total score” with ensifentrine, the researchers wrote.

Treatment with ensifentrine was significantly superior to a placebo at improving quality of life in ENHANCE-1 at three and six months. However, in ENHANCE-2, quality-of-life differences relative to a placebo failed to reach statistical significance.

Side effects occurred about as frequently in patients on ensifentrine as in those on a placebo, both in ENHANCE-1 (46.3% vs. 40.3%) and ENHANCE-2 (35.3% vs. 35.4%).

Only upper respiratory tract infections were significantly more common in the ensifentrine group than in the placebo group (2.1% vs. 1.8%) in the ENHANCE-1 trial.

“Hundreds of millions of people around the world are suffering with COPD,” Zaccardelli said in the release, adding that “this NDA acceptance brings us a step closer to our goal of delivering ensifentrine to a broad population of patients suffering from COPD.”

Source link