Regeneron and Sanofi Announce Positive Results from Phase 2b Study of Dupilumab in Patients with Moderate-to-Severe Asthma

Regeneron Pharmaceuticals and Sanofi have announced positive results from the interim analysis of a dose-ranging Phase IIb study of dupilumab in adult patients with uncontrolled moderate-to-severe asthma.  Dupilumab is an investigational therapy blocking IL-4 and IL-13, two cytokines required for the Th2 immune response.

"Many have thought that targeting the Th2 pathway in asthma would limit benefit to a subset of asthmatics, such as those with high eosinophils. In this study, blocking IL-4/IL-13 signaling with dupilumab improved lung function and reduced severe exacerbations in the broader study population," said Elias Zerhouni, MD, President, Global R&D, Sanofi. "Based on these results, we plan to move dupilumab into Phase 3 clinical development in patients with moderate-to-severe uncontrolled asthma."

In the study, the three highest doses of dupilumab in combination with standard-of-care therapy met the primary endpoint of a statistically significant improvement from baseline in forced expiratory volume over one second (FEV1, a standard measure of lung function) at Week 12 in patients with high blood eosinophils (greater than or equal to 300 cells/microliter), as compared to placebo in combination with standard-of-care therapy. In addition, two doses of dupilumab (200 mg every other week and 300 mg every other week) showed a statistically significant improvement in mean percent change in FEV1, as well as a reduction in severe exacerbations, in both the high eosinophils and overall study population.

Key results included

• In the high eosinophils patient group: Mean improvements from baseline in FEV1 (and mean percent change in FEV1) at 12 weeks, the primary (and a secondary) endpoint of the study were: 390 mL (26%) dupilumab 300 mg every other week (Q2W); 430 mL (26%) dupilumab 200 mg Q2W; 180 mL (10%) placebo. (p less than 0.01)
• In the overall population: Mean improvements from baseline in FEV1 at 12 weeks (and mean percent change in FEV1) were: 280 mL (18%) dupilumab 300 mg Q2W; 310 mL (18%) dupilumab 200 mg Q2W; 120 mL (6%) placebo. (p less than 0.001)
• In both the high eosinophils patient group and overall patient group: Dupilumab showed a reduction in adjusted annualized rate of severe exacerbations compared to placebo (64–75% reduction, p less than 0.05 for high eosinophils group and p less than 0.01 for the overall population).
• These results were based on a pre-specified interim analysis, which occurred when all patients had reached Week 12 of the 24-week treatment period; the average treatment duration at the time of the analysis was 21.5 weeks. The final analyses on exacerbations and safety will occur at 24 weeks.

The most common adverse event was injection site reaction, which was more frequent in the four dupilumab dose groups (13–25%) compared to placebo (12%). Other common adverse events in the study included upper respiratory tract infection (10–13% dupilumab; 13% placebo), headache (5–10% dupilumab; 8% placebo), nasopharyngitis (3–10% dupilumab; 6% placebo) and bronchitis (5–8% dupilumab; 8% placebo). The incidence of infections was balanced across treatment groups (42–45% dupilumab; 46% placebo), as was the incidence of serious adverse events (3–7% dupilumab; 5% placebo).

"Patients with moderate-to-severe asthma have a high unmet medical need, often struggling with daily symptoms and recurring asthma attacks, despite the use of inhaled steroids, long-acting beta agonists and rescue medications," said George D. Yancopoulos, MD, PhD, Chief Scientific Officer of Regeneron and President of Regeneron Laboratories. "This trial is encouraging given the positive results observed on the most clinically meaningful endpoints — FEV1, a key measure of lung function, and asthma exacerbations — were seen on top of ongoing background therapy. We look forward to continued investigation in further studies."