Phase III trial of Dupixent meets endpoints in eosinophilic esophagitis.- Sanofi/Regeneron Pharma

Sanofi and Regeneron Pharmaceuticals announced positive results from Part A of the pivotal Phase III trial evaluating Dupixent (dupilumab) in patients 12 years and older with eosinophilic esophagitis (EoE). The trial met both of its co-primary endpoints, as well as all key secondary endpoints. Dupixent is the first and only biologic to show positive and clinically-meaningful results in this population as part of a Phase III trial. An ongoing Part B portion of the Phase III trial evaluates an additional Dupixent dosing regimen. Part A of the trial enrolled 81 patients (42 with Dupixent, 39 with placebo) aged 12 years and older with EoE, as determined by histological and patient-reported measures. The co-primary endpoints assessed the change from baseline in the Dysphagia Symptom Questionnaire (DSQ), a patient-reported measure of difficulty swallowing, and the proportion of patients achieving peak esophageal intraepithelial eosinophil count of <=6 eos/hpf, a measure of an esophageal inflammation, at 24 weeks.

Patients treated with Dupixent 300 mg weekly experienced the following changes by week 24 from baseline: a 69% reduction in disease symptoms compared to 32% for placebo (p=0.0002). Disease symptoms were measured by the DSQ scale, where patients experienced a 21.92 point improvement with Dupixent compared to a 9.60 point improvement for placebo, on a 0-84 scale (p=0.0004), the co-primary endpoint; baseline DSQ scores were approximately 34 points. A 60% reduction in their esophageal eosinophilic count to a normal range compared to 5% for placebo (p<0.0001), the co-primary endpoint. This was measured by the proportion of patients who achieved a peak esophageal intraepithelial eosinophil count of <=6 eos/hpf (a normal range); mean baseline peak levels were 89 eos/hpf. A 39% reduction in abnormal endoscopic findings, compared to 0.6% worsening for placebo. This was measured by the EoE Endoscopic Reference Score (EoE-EREFS), where patients experienced a 3.2 point reduction with Dupixent compared to a 0.3 point reduction for placebo (p<0.0001).

The trial demonstrated similar safety results to the known safety profile of Dupixent in its approved indications. For the 24-week treatment period, overall rates of adverse events were 86% for Dupixent and 82% for placebo. Adverse events that were more commonly observed with Dupixent included injection site reactions (n=15 for Dupixent and n=12 for placebo) and upper respiratory-tract infections (n=11 for Dupixent and n=6 for placebo). There was one treatment discontinuation in the Dupixent group due to arthralgia. Detailed results from this trial will be presented at an upcoming medical meeting.