Dupilumab Is the First Investigational Biologic to Significantly Improve Lung Function in Patients With COPD

Dupilumab (Dupixent; Sanofi) is the first and only investigational biologic to significantly improve lung function at 12 and 52 weeks and significantly reduce severe acute exacerbations compared to placebo in adults with chronic obstructive pulmonary disease (COPD), according to authors who presented positive phase 3 topline results at the 2023 American Thoracic Society (ATS) International Conference.

Counseling on inhaler technique is crucial for helping patients with COPD have maximal efficacy with their therapy. Credit: peterschreiber.media - stock.adobe.com.

The findings—which were published in the New England Journal of Medicine—showed that dupilumab met the primary endpoint of the study regarding the yearly rate of acute moderate or severe COPD exacerbations. Specifically, the results showed that the treatment reduced exacerbations by 30% in 52 weeks.

"I've seen patients with uncontrolled [COPD] struggle for far too long with the debilitating symptoms of this progressive disease—with limited, incremental improvement on current treatment options,” said co-principal investigator Surya Bhatt, MD, MSPh, Birmingham Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama, in a recent press release.

COPD is a life-threatening respiratory disease that damages the lungs, leading to lung function decline that can result in hospitalization or death. Estimates suggest that 300,000 people in the United States have uncontrolled COPD with evidence of type 2 inflammation.

Recurrent exacerbations—which include symptoms of breathlessness and persistent cough— are treated with systemic corticosteroids, and the disease is associated with significant health and economic burden. Smoking can be a significant risk factor for COPD, and even those who have quit have a higher risk. Investigators are currently conducting a COPD program assessed in 2 clinical trials to evaluate dupilumab for patients with uncontrolled COPD who have received standard of care (SoC).

BOREAS is the first of the trials; it is a randomized, phase 3, double-blind, placebo-controlled trial designed to assess efficacy and safety of dupilumab in 939 adults who were current or former smokers with moderate to severe COPD and evidence (blood eosinophils of 300 cells/µL) of type 2 inflammation. During the BOREAS trial, 468 patients were randomized to the dupilumab arm, and 471 to the placebo arm.

For 52 weeks, patients received dupilumab or placebo every 2 weeks alongside maximal SoC inhaled triplet therapy, which includes inhaled corticosteroids, long-acting beta agonists, and long-acting muscarinic antagonists.

Compared to placebo, dupilumab significantly reduced exacerbations at 52 weeks (30% reduction). In addition, patients experienced an improvement in lung function at 12 weeks from baseline—with improvement persisting at 52 weeks. Patients also experienced improvements in health-related quality of life at 4 weeks and a reduction in respiratory symptom severity at 52 weeks.

“Dupilumab helped improve health-related quality of life measures, which, from my years of experience as a physician, are just as meaningful for patients as being able to breathe easier,” Bhatt said in the press release.

The general safety profile of dupilumab was consistent with previous findings; 77% of patients experienced adverse events (AEs), the most common including headache (8.1%), diarrhea (5.3%), and back pain (5.1%). Both dupilumab and placebo had similar AEs that led to death at 1.7% and 1.5%, respectively.

Dupilumab is a fully human monoclonal antibody that can inhibit the signaling of pathways that drive type 2 inflammation. It is already approved in certain countries for the treatment of atopic dermatitis and asthma, chronic rhinosinusitis with nasal polyposis, eosinophilic esophagitis, and prurigo nodularis.

“This trial showed that dupilumab has the potential to impact the vicious cycle of exacerbations and lung function decline in patients with uncontrolled COPD with type 2 inflammation, and significantly improve respiratory symptoms,” Bhatt said in the press release.

Reference

Sanofi. Press Release: Dupixent® (dupilumab) late-breaking Phase 3 COPD results presented at ATS and simultaneously published in the New England Journal of Medicine. News Release. May 21, 2023. Accessed on May 23, 2023. https://www.sanofi.com/en/media-room/press-releases/2023/2023-05-21-18-17-12-2672904