NOTUS trial met its primary endpoint with overwhelming efficacy, showing Dupixent significantly reduced exacerbations by 34% compared to placebo in patients with moderate-to-severe COPD with evidence of type 2 inflammation (i.e., blood eosinophils ≥300 cells per μL), confirming results from the landmark BOREAS pivotal trial

Dupixent rapidly and significantly improved lung function (139 mL in FEV1) compared to placebo (57 mL in FEV1) at 12 weeks

Supplemental BLA submission planned by end of 2023

Approximately 300,000 people in the United States live with uncontrolled COPD with evidence of type 2 inflammation; no new treatment approaches approved for more than a decade

TARRYTOWN, N.Y. and PARIS, Nov. 27, 2023 (GLOBE NEWSWIRE) -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Sanofi today announced that the second Dupixent® (dupilumab) investigational Phase 3 chronic obstructive pulmonary disease (COPD) trial (NOTUS) showed that Dupixent significantly reduced (34%) exacerbations, confirming positive results from the landmark Phase 3 BOREAS trial. The NOTUS trial also confirmed that treatment with Dupixent led to rapid and significant improvements in lung function by 12 weeks and were sustained at 52 weeks.

The NOTUS trial evaluated the investigational use of Dupixent compared to placebo in adults currently on maximal standard-of-care inhaled therapy (triple therapy) with uncontrolled COPD and evidence of type 2 inflammation (i.e., blood eosinophils ≥300 cells per μL). These results were from an interim analysis and, given the overwhelming positive efficacy of the primary endpoint, will be considered the primary analysis of the trial. Regeneron and Sanofi plan to submit the data from this replicate trial, along with positive results from the Phase 3 BOREAS trial to the U.S. Food and Drug Administration (FDA) by the end of the year.

“We are highly encouraged by these remarkable results from NOTUS showing a 34% reduction in COPD exacerbations compared to placebo, confirming the unprecedented results from our first Phase 3 trial, BOREAS,” said George D. Yancopoulos, M.D., Ph.D., Board Co-Chair, President and Chief Scientific Officer at Regeneron, and a principal inventor of Dupixent. “These results demonstrate the important role of type 2 inflammation in yet another chronic and debilitating disease, and the ability of Dupixent to address this inflammation. We are working to submit these data rapidly to the FDA.”

Earlier this year, the FDA granted Breakthrough Therapy designation for Dupixent as an add-on maintenance treatment in adult patients with uncontrolled COPD associated with a history of exacerbations and an eosinophilic phenotype based on the positive results from BOREAS.

“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 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,” said Naimish Patel, M.D., Head of Global Development, Immunology and Inflammation at Sanofi. “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.”

The NOTUS trial included 935 adults who were current or former smokers aged 40 to 85 years and randomized to receive Dupixent (n=470) or placebo (n=465), which was added to maximal standard-of-care inhaled therapy. Patients receiving Dupixent compared to placebo experienced:

• 34% reduction in moderate or severe acute COPD exacerbations over 52 weeks (p=0.0002), the primary endpoint.
• Improved lung function from baseline by 139 mL at 12 weeks compared to 57 mL for placebo (p=0.0001), with the benefit versus placebo sustained at week 52 (115 mL for Dupixent versus 54 mL for placebo, p=0.0182).

The safety results were generally consistent with the known safety profile of Dupixent in its approved indications. Overall rates of adverse events (AE) were 67% for Dupixent and 66% for placebo. AEs more commonly observed with Dupixent (≥5% and ≥1% imbalance) compared to placebo included COVID-19 (9.4% Dupixent, 8.2% placebo), nasopharyngitis (6.2% Dupixent, 5.2% placebo) and headache (7.5% Dupixent, 6.5% placebo). AEs more commonly observed with placebo compared to Dupixent included COPD (7.8% placebo, 4.9% Dupixent). AEs leading to deaths were 2.6% for Dupixent and 1.5% for placebo.

Detailed results from the NOTUS trial are planned for presentation at a future scientific forum.

The efficacy results in NOTUS were consistent with the previously announced results in BOREAS. BOREAS results showed:

• 30% reduction in moderate or severe acute COPD exacerbations over 52 weeks (p=0.0005), the primary endpoint.
• Improved lung function from baseline by 160 mL at 12 weeks compared to 77 mL for placebo (p