Ohtuvayre effective across key patient subgroups: ENHANCE trials
Inhaled therapy approved in US earlier this year for adults with COPD
Ohtuvayre (ensifentrine), an inhaled therapy approved in the U.S. earlier this year for adults with chronic obstructive pulmonary disease (COPD), has been found to safely and effectively lead to clinical improvements among COPD patients regardless of disease severity, smoking history, and chronic bronchitis history.
Chronic bronchitis is a common form of COPD marked by lung inflammation, increased mucus production, and cough with productive mucus for two consecutive years.
These results come from several post-hoc analyses of pooled data from the Phase 3 ENHANCE clinical trials, whose top-line data supported Ohtuvayre’s June approval in the U.S. as an inhaled maintenance therapy for COPD. Post-hoc analyses are those planned and done after a trial has ended.
The new findings were shared by developer Verona Pharma across a series of presentations at the CHEST Annual Meeting, held Oct. 6-9 in Boston.
“Since the FDA approved Ohtuvayre … we have seen significant interest in prescribing from physicians with patients struggling with persistent COPD symptoms,” David Zaccardelli, Verona’s president and CEO, said in a statement emailed to COPD News Today.
“Ohtuvayre can potentially improve lung function, alleviate symptoms, reduce exacerbation rates and improve overall quality of life, regardless of the severity of COPD, smoking history, or the presence of chronic bronchitis,” Zaccardelli said. “These benefits are supported by the recent analyses of our Phase 3 ENHANCE data presented at CHEST 2024.”
New analyses show Ohtuvaryre widens airways, eases inflammation
COPD is a chronic lung disorder marked by progressive airway inflammation and airway narrowing or obstruction.
Ohtuvaryre works to simultaneously widen the airways — known as bronchodilation — ease inflammation, and promote mucus clearance from the lungs by suppressing the activity of two enzymes called phosphodiesterase 3 and phosphodiesterase 4.
The ENHANCE-1 (NCT04535986) and ENHANCE-2 (NCT04542057) trials collectively enrolled more than 1,500 current or former adult smokers with moderate to severe COPD. The participants were randomly assigned to take either Ohtuvayre (3 mg) or a placebo twice daily via a nebulizer for about six months. Stable regimens of other standard-of-care inhaled therapies were allowed.
Top-line results showed that Ohtuvaryre significantly improved lung function, lowered the rate of pulmonary exacerbations — periods of sudden lung symptom worsening — and tended to ease COPD symptoms relative to the placebo. Benefits were observed regardless of patients’ use of other bronchodilator medications or the individuals’ exacerbation history.
In an oral presentation titled “Ensifentrine Improved Lung Function, Symptoms, and Quality of Life Regardless of COPD Severity,” Jessica M. Bon, MD, of Wake Forest University School of Medicine, shared Ohtuvarye’s effects in subgroups of ENHANCE participants stratified by COPD severity.
The results showed that Ohtuvaryre led to significant improvements in lung function after three months relative to the placebo, regardless of whether patients had moderate or severe airflow obstruction at the study’s start.
The therapy also was superior to the placebo at easing COPD symptoms, including breathlessness, known as dyspnea, and improving life quality in both disease severity groups. Differences between the treatment and placebo groups reached statistical significance and/or the threshold to be considered clinically meaningful at several time points.
“[Ohtuvaryre] provides a novel mechanism of action for clinically meaningful improvements in lung function, symptoms, and quality of life regardless of COPD severity,” Bonn said. “This is especially important given that as … lung function declines over time, additional … mechanisms to maximize treatment effects are needed.”
In “Ensifentrine Improved Lung Function and Reduced Exacerbation Rate and Risk in Patients with COPD Regardless of Smoking Status,” another oral presentation, Verona’s Amy Dixon discussed outcomes for participants stratified by smoking status.
Lung function was significantly improved with Ohtuvaryre after three months compared with the placebo regardless of whether patients were current smokers or former smokers. The treatment also significantly lowered the risk of moderate or severe exacerbations relative to the placebo in both groups: by 43% in current smokers and by 40% in former smokers.
Benefits seen for patients regardless of disease severity, smoking history
Further findings from these patient subgroups were presented by William Stringer, MD, of the David Geffen School of Medicine at the University of California Los Angeles. That poster was titled “Ensifentrine Improved Symptoms and Quality of Life in Patients with Moderate-to-Severe COPD Regardless of Smoking Status.”
According to Stringer’s presentation, Ohtuvaryre led to early and sustained reductions in COPD symptoms relative to the placebo in both current and former smokers, with statistical significance and the threshold to be considered clinically meaningful reached at most time points.
[Ohtuvaryre] is a remarkable addition to COPD therapy. … It has the capacity to bronchodilate, reduce inflammation, augment [mucus] clearance, and reduce exacerbations in smokers and former smokers.
Treatment also was associated with clinically meaningful life quality improvements, which were significantly greater than those observed with the placebo only in the current smoker group.
“[Ohtuvaryre] is a remarkable addition to COPD therapy,” Stringer said in the release. “It has the capacity to bronchodilate, reduce inflammation, augment [mucus] clearance, and reduce exacerbations in smokers and former smokers.”
Finally, in a poster titled “Ensifentrine Improved Symptoms and Quality of Life in Patients with COPD Regardless of Bronchitis History,” Jill A. Ohar, MD, of the Wake Forest University School of Medicine, presented data on Ohtuvaryre’s effects on trial participants who either did or did not have chronic bronchitis.
Ohtuvaryre was superior to the placebo at easing COPD symptoms, including dyspnea, regardless of bronchitis history, with differences reaching statistical significance at nearly all time points. The treatment also tended to be associated with greater life quality gains.
Moreover, in patients with bronchitis and those without, Ohtuvaryre was associated with higher proportions of patients achieving clinically meaningful improvements across COPD symptom and life quality measures.
Across all analyses, the data generally showed that there were no key safety differences between patient subgroups.
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