FDA Accepts sBLA for Priority Review of Dupilumab for Uncontrolled COPD

The US Food and Drug Administration (FDA) has accepted the supplemental Biologics License Application (sBLA) for Priority Review for dupilumab (Dupixent), with the drug’s indication being as an add-on maintenance therapy for adults with uncontrolled chronic obstructive pulmonary disease (COPD).¹

COPD is a respiratory condition which is characterized by progressive declines in patients’ lung function, with breathlessness, cough, and excessive mucus being the known symptoms. COPD can lead to significant impairment in activities as it often results in recurrent acute exacerbations necessitating systemic corticosteroid treatment.

Dupilumab is a fully human monoclonal antibody which is known to inhibit interleukin (IL)-13 and IL-4 signaling pathways while not functioning as an immunosuppressant. It has been approved for conditions such as eczema, asthma, prurigo nodularis, and chronic spontaneous urticaria (CSU) and serves as a significant treatment for chronic diseases impacted by type 2 inflammation.

This new indication for COPD would mark the sixth for dupilumab, and the decision to accept the drug’s sBLA follows successful phase 3 findings on COPD. These findings from the phase 3 BOREAS and NOTUS studies demonstrated that the drug had met each of its primary endpoints.

During the BOREAS trial, dupilumab had led to a 30% reduction in patients’ moderate or severe acute COPD exacerbations over the course of 52 weeks (P = 0.0005), which had been the study’s primary endpoint.² It had also met several of its key secondary endpoints, such as improvement in lung function from baseline by 160 mL at 12 weeks compared to 77 mL for those in the placebo arm (P < 0.0001).

In the NOTUS trial, dupilumab had led to substantial reductions in COPD exacerbations by 34% versus placebo among those with moderate-to-severe COPD and evidence of type 2 inflammation, indicating overwhelming efficacy and the meeting of primary and secondary endpoints.³ These findings aligned with the results of the BOREAS study.

The safety data drawn from both trials had been shown to be consistent with the drug’s known safety profile in its previously-approved indications. The investigators had noted that adverse events more commonly seen with dupilumab had been COVID-19, back pains, diarrhea, headaches, and nasopharyngitis.¹

Following the successful phase 3 results, the FDA made its decision to accept the drug’s sBLA and a decision is slated for June 27, 2024. There are also regulatory submissions being undertaken for review processes in the European Union and in China.

Dupilumab is also being evaluated in other phase 3 studies for COPD with type 2 inflammation, CSU, chronic pruritus of unknown origin, and bullous pemphigoid. The drug’s potential for use with such conditions has yet to be fully assessed and reviewed by regulatory authorities.

References

1. ^{Dupixent® sBLA accepted for FDA Priority Review for treatment of COPD with type 2 inflammation. Regeneron. February 23, 2024. https://investor.regeneron.com/news-releases/news-release-details/dupixentr-dupilumab-sbla-accepted-fda-priority-review-treatment. Date accessed: February 23, 2024.}
2. ^{Dupixent® (dupilumab) demonstrates potential to become first biologic to treat COPD by showing significant reduction in exacerbations in pivotal trial. Regeneron. March 23, 2023. https://investor.regeneron.com/news-releases/news-release-details/dupixentr-dupilumab-demonstrates-potential-become-first-biologicDate accessed: February 23, 2024.}
3. ^{Dupixent® 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. November 27, 2023. https://investor.regeneron.com/news-releases/news-release-details/dupixentr-dupilumab-significantly-reduced-copd-exacerbations. Date accessed: February 23, 2024.}