FDA Grants Priority Review to Dupixent for Uncontrolled Chronic Obstructive Pulmonary Disease

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The FDA has granted Priority Review status to a supplemental Biologics License Application (sBLA) submitted by Regeneron Pharmaceuticals and Sanofi for Dupixent (dupilumab) as add-on maintenance therapy for adults with uncontrolled chronic obstructive pulmonary disease (COPD) with type 2 inflammation.¹ Data presented at the 2023 American Thoracic Society International Conference and published in the New England Journal of Medicine show Dupixent was the first and only novel biologic drug to significantly improve lung function and reduce severe acute exacerbations in adults with COPD.²

The human monoclonal antibody of the immunoglobulin G4 subclass acts as an interleukin (IL)-4 receptor alpha antagonist. Dupixent inhibits IL-4 and IL-13 signaling by specifically binding to the IL-4 receptor alpha subunit shared by the IL-4 and IL-13 receptor complexes. Dupixent inhibits IL-4 signaling through the type 1 receptor and both IL-4 and IL-13 signaling through the type 2 receptor. Through blocking the IL-4R alpha subunit, dupilumab inhibits IL-4 and IL-13 cytokine-induced responses, such as the release of proinflammatory cytokines, chemokines, and immunoglobulin E.³

Submission of the sBLA was based on findings from a pair of replicate, randomized, double-blind, placebo-controlled Phase III trials analyzing the efficacy and safety of the biologic in adults who were current or former smokers with uncontrolled COPD showing evidence of type 2 inflammation. The NOTUS trial included current or former smokers with moderate-to-severe COPD aged from 40 to 85 years, whereas the BOREAS trial included those aged 40 to 80 years.⁴

Investigators enrolled 1,874 patients in NOTUS and BOREAS showing evidence of type 2 inflammation, as measured by blood eosinophils ≥300 cells per µL. During the 52-week treatment period, patients were administered Dupixent or placebo every two weeks as an add on to maximal standard-of-care inhaled triple therapy, including inhaled corticosteroids, long-acting beta agonists, and long-acting muscarinic antagonists. The primary endpoint for both trials was the annualized rate of acute moderate or severe COPD exacerbations.

Dupixent achieved the primary endpoint in both trials, with decreased annualized moderate COPD exacerbations by 30% and severe acute exacerbations by 34%, respectively. Across both trials, Dupixent was found to rapidly and significantly improve lung function compared to placebo, which was sustained at 52 weeks.¹

“This is the first and only time an investigational biologic in COPD has shown a significant and clinically meaningful reduction in exacerbations in two Phase III trials and we are pleased that we can potentially deliver Dupixent faster to patients in need where no new advancements have been identified in over a decade,” Sanofi Head of Global Development, Immunology and Inflammation Naimish Patel, MD, said in a press release. “These data validate our belief that Dupixent has the potential to transform the treatment of moderate-to-severe COPD and given the significant unmet needs for patients with uncontrolled COPD, we are not stopping with Dupixent. Our second program in COPD, itepekimab, continues with data expected in 2025. If positive, Dupixent and itepekimab could emerge as treatments for approximately 80% of those suffering from moderate-to-severe COPD with recurrent exacerbations.”⁴

The FDA has assigned the sBLA with a Prescription Drug User Fee Act (PDUFA) date of June 27, 2024.

References

1. Dupixent® (Dupilumab) sBLA Accepted For FDA Priority Review For Treatment Of COPD With Type 2 Inflammation. Regeneron. News release. February 23, 2024. Accessed February 23, 2024. https://investor.regeneron.com/news-releases/news-release-details/dupixentr-dupilumab-sbla-accepted-fda-priority-review-treatment

2. 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 February 23, 2024. https://www.sanofi.com/en/media-room/press-releases/2023/2023-05-21-18-17-12-2672904

3. Anand P, Schneeweiss S, Mostaghimi A, Schneeweiss MC. Use patterns of systemic immunomodulators in the United States before and after dupilumab approval in adults with atopic dermatitis. Pharmacoepidemiol Drug Saf. 2022 Dec 17. doi: 10.1002/pds.5586. PMID: 36527432.

4. Dupixent® (Dupilumab) Significantly Reduced COPD Exacerbations in Second Positive Phase 3 Trial, Accelerating FDA Submission and Confirming Potential to Become First Approved Biologic For This Serious Disease. Regeneron. News release. November 27, 2023. Accessed February 23, 2024. https://investor.regeneron.com/news-releases/news-release-details/dupixentr-dupilumab-significantly-reduced-copd-exacerbations