Data From Phase 3 Trials Demonstrate Efficacy of Dupilumab for Treating COPD, Type 2 Inflammation

This article was originally published by Pharmacy Times^®. It has been lightly edited.

Investigators plan to submit a supplemental biologics license application (sBLA) for dupilumab (Dupixent; Sanofi, Regeneron) at the end of 2023 for the treatment of uncontrolled chronic obstructive pulmonary disease (COPD) and type 2 inflammation, according to a press release.

The submission is based on data from the phase 3 BOREAS and NOTUS trials, which demonstrated that dupilumab can significantly reduce COPD exacerbations.

“This is the first and only time an investigational biologic in COPD has shown a significant and clinically meaningful reduction in exacerbations in 2 Phase 3 trials,” said Naimish Patel, MD, head of Global Development, Immunology, and Inflammation at Sanofi, in the press release.

At the interim analysis of NOTUS, the fully human monoclonal antibody reduced 34% more exacerbations of COPD than placebo in patients with moderate-to-severe COPD with evidence of type 2 inflammation. It also improved lung function (more than 2-times higher mL in FEV₁ at 12 weeks) and sustained these improvements at 1 year.

NOTUS is a replicate trial to BOREAS, and it evaluated the safety and efficacy of dupilumab for patients taking the maximal standard-of-care inhaled therapy (triple therapy) for uncontrolled COPD who have type 2 inflammation, such as high blood eosinophils.

BOREAS was the first phase 3 trial to evaluate dupilumab for this patient population. During BOREAS, dupilumab met the primary endpoint by reducing exacerbations of moderate or severe acute COPD at 52 weeks (P = .0005; 30% reduction). Dupilumab also significantly improved lung function at 12 weeks compared to placebo (P < .0001; 160 mL versus 77 mL, respectively), and benefits lasted up to week 52 (P = .0003).

COPD

Image credit: Ivelin Radkov - stock.adobe.com

“These results demonstrate the important role of type 2 inflammation in yet another chronic and debilitating disease, and the ability of [dupilumab] to address this inflammation,” said George D. Yancopoulos, MD, PhD, board co-chair, president, and chief scientific officer at Regeneron.

In NOTUS, 67% of patients in the experimental arm had adverse events (AEs); this was 66% in the placebo arm. The most common AEs associated with dupilumab were COVID-19, nasopharyngitis, and headache. In BOREAS, 77% and 76% of patients had AEs, respectively, and the most common AEs associated with dupilumab were headache, diarrhea, and back pain.

Sanofi and Regeneron jointly developed dupilumab, which works by inhibiting the signaling of the interleukin-4 (IL-4) and interleukin-13 (IL-13) pathways. The partners also submitted an application to the European Medicines Agency for the approval of dupilumab as a treatment of uncontrolled COPD with type 2 inflammation, which is under review.

“These data validate our belief that [dupilumab] has the potential to transform the treatment of moderate-to-severe COPD,” Patel said in the press release.

As for next steps, Yancopoulous said they are "working to submit these data rapidly to the FDA."

Reference

Press Release: 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. Sanofi. November 27, 2023. Accessed on November 27, 2023. https://www.sanofi.com/en/media-room/press-releases/2023/2023-11-27-06-30-00-2785836