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FDA Accepts Dupilumab sBLA for Priority Review for Treatment of COPD with Type 2 Inflammation
A PDUFA date of June 27, 2024 has been set for approval of a 6th dupilimab indication - as add-on therapy for individuals with COPD and eosinophilic inflammation.
Sanofi and Regeneron Pharmaceuticals announced today that the companies’ supplemental biologics license application (sBLA) for dupilumab (Dupixent) as add-on maintenance therapy for adults with uncontrolled chronic obstructive pulmonary disease (COPD) has been accepted for priority review by the US Food and Drug Administration (FDA) with a target action date for the FDA decision of June 27, 2024.
Courtesy of US FDA
Foundational data for the US sBLA and regulatory submissions in Europe and China are from 2 phase 3 clinical trials that analyzed the safety of dupilumab specifically in adults who were current or former smokers whose COPD symptoms were uncontrolled and who had evidence of type 2 (T2) inflammation. All study participants in the NOTUS and BOREAS trials were already receiving maximal standard of care inhaled therapy, with the majority prescribed triple therapy.
The NOTUS trial met its primary endpoint “with overwhelming efficacy,” the companies reported previously (ref), showing that dupilumab significantly reduced annualized moderate or severe COPD exacerbations by 34% compared with placebo. The replicate phase 3 BOREAS trial returned equivalent results, with disease exacerbations reduced by 30%. Sanofi and Regeneron reported that improvements in lung function were “rapid and significant,” observed in some dupilumab-treated patients as early as 12 weeks into treatment. The gains were sustained at 52 weeks of follow-up, the companies stated.
“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 3 trials, Naimish Patel, MD, Sanofi head of global development, immunology, and inflammation said in a statement concerning submission of the sBLA. The development partners emphasize that there have been no new treatments for COPD with evidence of T2 inflammation for more than a decade.
The 2 phase 3 trials: NOTUS, BOREAS
Participants in NOTUS (n=935) are aged 40 to 85 years and in BOREAS (n=939) were aged 40 to 80 years. All participants had evidence of type 2 inflammation (ie, blood eosinophils ≥300 cells/uL) and were receiving maximal standard-of-care inhaled therapy.
During the 52-week treatment period in both trials, participants were randomly assigned to receive dupilumab or placebo every 2 two weeks added to a maximal standard-of-care inhaled triple therapy of inhaled corticosteroids, long-acting ß-agonists, and long-acting muscarinic antagonists.
Key findings from NOTUS
- 34% reduction in moderate or severe acute COPD exacerbations over 52 weeks (P = .0002), the primary endpoint.
- Improved lung function from baseline by 139 mL in FEV1 at 12 weeks vs 57 mL for placebo (P = .0001), with the benefit versus placebo sustained at week 52 (115 mL in FEV1 for dupilumab vs 54 mL for placebo, P = .0182), both of which were key secondary endpoints.
Key findings from BOREAS
- 30% reduction in moderate or severe acute COPD exacerbations over 52 weeks (P = .0005), the primary endpoint.
- Improved lung function from baseline by 160 mL in FEV1 at 12 weeks compared to 77 mL for placebo (P < .001), with the benefit versus placebo sustained through week 52 (P = .003).
The companies said that the safety results in both studies were consistent with the known safety profile of dupilumab in its 5 current indications. Back pain, COVID-19, diarrhea, headache and nasopharyngitis were seen more commonly (≥5%) with dupilumab treatment than placebo in either trial, according to the statement.
