Dupixent met co-primary endpoints in Part A of Phase 3 trial: Regeneron, Sanofi

Paris and Tarrytown: Sanofi and Pharmaceuticals, Inc. has announced positive results from Part A of the pivotal Phase 3 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 3 trial. An ongoing Part B portion of the Phase 3 trial evaluates an additional Dupixent dosing regimen.

EoE is a chronic and progressive type 2 inflammatory disease that damages the esophagus and prevents it from working properly, leading to difficulties swallowing. If untreated, symptoms and inflammation can progress, causing functional damage and scarring of the esophagus. EoE can lead to esophageal food impaction, requiring immediate emergency room visits. Almost half of the patients in this trial had prior procedures such as dilation of their esophagus, and almost three-quarters had previously been treated with corticosteroids.

In the U.S., there are approximately 160,000 patients with EoE who are currently treated, of which an estimated 50,000 have failed multiple treatments. There are currently no therapies approved by the U.S. Food and Drug Administration (FDA).

"Eosinophilic esophagitis can be debilitating, and there are no approved treatment options. It impacts patients' ability to eat, causes severe pain, and often results in repeated emergency room visits and medical procedures," said George D. Yancopoulos, M.D., Ph.D., Co-Founder, President and Chief Scientific Officer of Regeneron. "These data are particularly impressive as Dupixent not only dramatically reduced eosinophils in the esophagus, but also improved all clinical, anatomic and histologic measures of the disease. In the past, EoE was thought to be a disease caused by eosinophils, but other biologics that decrease the eosinophils in the esophagus did not demonstrate consistent clinical or anatomical improvements. These Dupixent results demonstrate EoE is caused by multiple aspects of type 2 inflammation, driven by interleukin-4 and interleukin-13. EoE is the fourth atopic or type 2 inflammatory disease in which Dupixent has pivotal data demonstrating significant efficacy."'

"These data demonstrate Dupixent's potential to continue to address treatment gaps across the spectrum of type 2 inflammatory diseases as common as asthma and as rare as eosinophilic esophagitis," said John Reed, M.D, Ph.D., Global Head of Research and Development at Sanofi. "For the first time in a Phase 3 trial, patients reported an improvement in their ability to swallow food. For patients with eosinophilic esophagitis who are living with restricted diets and, in some cases, repeated hospital interventions, these findings are encouraging."

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:

• 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.
• 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.
• 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. Dupixent received Orphan Drug Designation from the FDA in 2017 for the potential treatment of EoE. This status is given to investigational medicines intended for the safe and effective treatment of rare diseases that affect fewer than 200,000 people in the U.S.

The potential use of Dupixent in eosinophilic esophagitis is currently under clinical development, and the safety and efficacy have not been evaluated by any regulatory authority.

Dupixent is a fully-human monoclonal antibody that inhibits the signaling of the interleukin-4 (IL-4) and interleukin-13 (IL-13) proteins. Data from Dupixent clinical trials have shown that IL-4 and IL-13 are key drivers of the type 2 inflammation that plays a major role in atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis, and eosinophilic esophagitis.

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