FDA Extends PDUFA Date for Dupixent in COPD, Requesting Additional Data From BOREAS and NOTUS Trials

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The FDA has extended the Prescription Drug User Fee Act (PDUFA) target action date by three months for the priority review of a supplemental Biologics License Application (sBLA) filed by Sanofi and Regeneron for Dupixent (dupilumab) as an add-on maintenance treatment for certain adults with uncontrolled chronic obstructive pulmonary disease (COPD). The agency is seeking to evaluate additional efficacy analyses of the drug from the pivotal BOREAS and NOTUS trials, but did not raise concerns about approving the sBLA, according to Sanofi.¹

“Based on the submission of these analyses earlier in May, the agency has now determined that this additional information constituted a major amendment to the sBLA and extended the target action date accordingly,” Sanofi stated in a press release.¹ “Sanofi and Regeneron are confident that the additional analyses strongly support the approval of Dupixent in COPD with evidence of type 2 inflammation, and are committed to working with the FDA to bring Dupixent to patients living with uncontrolled COPD as quickly as possible.”

The new PDUFA date for the sBLA is September 27, 2024.

Dupixent, a 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.²

In data published in the New England Journal of Medicine, Dupixent was the first and only novel biologic medication shown to significantly improve lung function and decrease severe acute exacerbations in adults with COPD.³

The replicate, randomized, double-blind, placebo-controlled, Phase III BOREAS and NOTUS trials evaluated the efficacy and safety of Dupixent in 1,874 adult patients who were current or former smokers with uncontrolled COPD showing evidence of type 2 inflammation. The NOTUS trial enrolled current or former smokers with moderate-to-severe COPD, aged between 40 and 85 years, while BOREAS enrolled patients between 40 and 80 years of age.⁴

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

Dupixent achieved the primary endpoint in both trials, lowering annualized moderate COPD exacerbations by 30% and severe acute exacerbations by 34%, respectively. Across both the NOTUS and BOREAS trials, Dupixent demonstrated a rapid and significant improvement in lung function compared to placebo, which was sustained across the 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 prior 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

References

1. Update on FDA priority review of Dupixent for the treatment of COPD patients with type 2 inflammation. News release. Sanofi. May 31, 2024. Accessed May 31, 2024. https://www.news.sanofi.us/2024-05-31-Update-on-FDA-priority-review-of-Dupixent-for-the-treatment-of-COPD-patients-with-type-2-inflammation

2. 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.

3. 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 May 31, 2024. https://www.sanofi.com/en/media-room/press-releases/2023/2023-05-21-18-17-12-2672904

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 May 31, 2024. https://investor.regeneron.com/news-releases/news-release-details/dupixentr-dupilumab-significantly-reduced-copd-exacerbations