Sanofi/Regeneron's IL-33 Antibody REGN3500 Meets Phase 2 Endpoint in Asthma but Lags Behind Dupixent

Compiled by Fan Dongdong

Recently, Sanofi and Regeneron jointly announced that the Phase 2 trial of the IL-33 antibody REGN3500 for asthma had met its primary endpoint. However, the efficacy of REGN3500 as monotherapy was numerically inferior to that of Dupixent, and the therapeutic effect of combination therapy with Dupixent was also suboptimal.

REGN3500 is a fully human monoclonal antibody that inhibits interleukin-33 (IL-33), a protein believed to play a key role in type 1 and type 2 inflammation. Preclinical studies have demonstrated that REGN3500 can block several biomarkers associated with both types of inflammation. In moderate-to-severe asthma, this novel therapy may suppress multiple potential sources of inflammation, thereby helping to address asthma exacerbations.

Currently, Sanofi and Regeneron are conducting a series of clinical trials of REGN3500 in asthma, atopic dermatitis, and chronic obstructive pulmonary disease to evaluate the therapeutic effects of inhibiting the IL-33 protein in these patient populations.

This asthma trial enrolled a total of 296 patients with moderate-to-severe asthma. The trial results demonstrated that REGN3500 was superior to placebo in the proportion of patients achieving asthma control, thereby meeting the primary endpoint. Furthermore, as measured by FEV1, the therapy yielded a statistically significant improvement in lung function, thus achieving the key secondary endpoint. However, the data for REGN3500 were less favorable compared with Dupixent; patients receiving Dupixent outperformed those in the REGN3500 group across all trial endpoints. Moreover, the combination therapy of Dupixent and REGN3500 did not demonstrate superior efficacy compared with Dupixent monotherapy.

Regarding the incidence of adverse events (AEs), the rates were 61.6% in the REGN3500 group, 66.2% in the REGN3500 + Dupixent group, 56.8% in the Dupixent group, and 64.9% in the placebo group. However, the incidence of serious adverse events leading to treatment discontinuation was low in this trial.

Sanofi/Regeneron pointed out that REGN3500 performed best in patients with blood eosinophil levels exceeding 300 cells/μL, but Dupixent was also most effective in this population. Efficacy data from additional trials have not yet been disclosed. However, these findings lead to the conclusion that it may be difficult for REGN3500 to replace Dupixent in the future.

Jefferies analysts wrote in a report, “The results of this trial indicate that IL-33 monotherapy is less effective than Dupixent, and the combination therapy with Dupixent did not yield significant therapeutic benefits. It may therefore be considered that the role of IL-33 inhibitors in asthma treatment is limited.”

George D. Yancopoulos, M.D., President and Chief Scientific Officer of Regeneron, stated, “This trial demonstrates that REGN3500 may provide an alternative targeted therapy for patients with asthma. We look forward to continuing our collaboration with Sanofi to advance ongoing trials in atopic dermatitis and chronic obstructive pulmonary disease.”

References:

1、Sanofi and Regeneron announce positive topline Phase 2 results for IL-33 antibody in asthma

2、Sanofi, Regeneron asthma prospect struggles against Dupixent