Dupixent Achieves Success in Phase 3 Trial for Eosinophilic Esophagitis, Poised to Become First Approved Therapy

Compiled by Keke

Regeneron and Sanofi Announce Positive Topline Results from Part A of a Pivotal Phase 3 Trial of Dupixent (dupilumab) in Patients Aged 12 Years and Older with Eosinophilic Esophagitis (EoE)Recently, Regeneron and Sanofi announced positive results from Part A of a pivotal Phase 3 clinical trial evaluating Dupixent (dupilumab) in patients aged 12 years and older with eosinophilic esophagitis (EoE). The trial met its primary co-endpoints and all key secondary endpoints, making Dupixent the first and only biologic to demonstrate positive and clinically meaningful outcomes in this patient population. Part B of this Phase 3 trial is currently assessing an additional Dupixent dosing regimen.

It is reported that this randomized, double-blind, placebo-controlled Phase 3 trial was designed to evaluate the efficacy and safety of Dupixent in adolescent and adult patients with eosinophilic esophagitis (EoE). Part A of the trial enrolled 81 patients, assessed using histological and patient-reported outcomes; notably, 85% of these patients had at least one concurrent allergic condition, such as allergic rhinitis, food allergy, or asthma. During the 24-week treatment period, patients received weekly subcutaneous injections of either 300 mg Dupixent (n=42) or placebo (n=39). The co-primary endpoints were the change from baseline in the Dysphagia Symptom Questionnaire (DSQ) score and the proportion of patients achieving a peak esophageal intraepithelial eosinophil count of ≤6 eos/hpf at Week 24.

The results showed that patients treated with Dupixent experienced the following changes from baseline to Week 24:

Disease symptoms were reduced by 69% compared with the placebo group (32%) (p=0.0002). Disease symptoms were measured using the DSQ scale; on a 0–84 scale, patients in the Dupixent group improved by 21.92 points, while those in the placebo group improved by 9.60 points (p=0.0004), thereby meeting the primary endpoint.

The proportion of patients achieving an esophageal intraepithelial eosinophil count of ≤6 eos/hpf (normal range) was used as the measure; 60% of patients in the treatment group achieved a reduction in esophageal eosinophil counts to within the normal range, compared with 5% in the placebo group (p<0.0001), thereby meeting the co-primary endpoint.

Abnormal endoscopic findings decreased by 39%, compared with 0.6% in the placebo group. As measured by the EoE Endoscopic Reference Score, patients in the Dupixent group showed a reduction of 3.2 points, versus 0.3 points in the placebo group (p<0.0001).

In the trial, Dupixent demonstrated a safety profile consistent with that observed in its approved indications. During the treatment period, the overall incidence of adverse events was 86% for Dupixent and 82% for placebo. The most common adverse events associated with the drug included injection-site reactions and upper respiratory tract infections. One patient in the Dupixent group discontinued treatment due to arthralgia.

Dr. George D. Yancopoulos, Co-founder, President, and Chief Scientific Officer of Regeneron, stated: “Eosinophilic esophagitis impairs patients’ ability to eat, causes severe pain, and often leads to recurrent emergency department visits and medical encounters, with no approved treatment options currently available. The data from this trial are impressive; Dupixent not only significantly reduced eosinophils in the esophagus but also improved all clinical, endoscopic, and histologic endpoints of the disease.”

Dr. John Reed, Global Head of Research and Development at Sanofi, stated, “These data indicate that Dupixent has the potential to address unmet therapeutic needs in type 2 inflammatory diseases, including rare conditions such as asthma and eosinophilic esophagitis. In this trial, patients demonstrated improved ability to swallow food for the first time.”

Eosinophilic esophagitis (EoE) is a chronic, progressive type 2 inflammatory disease that impairs esophageal function and leads to dysphagia. If left untreated, symptoms and inflammation may progress, resulting in functional impairment and esophageal scarring. Patients with EoE require dietary restrictions and, in some cases, repeated medical interventions. In the United States, approximately 160,000 patients are currently receiving treatment for EoE, among whom about 50,000 have experienced multiple treatment failures. In 2017, Dupixent was granted orphan drug designation by the U.S. Food and Drug Administration (FDA) for the potential treatment of EoE.

Dupixent is a fully human monoclonal antibody that specifically inhibits the signaling of key proteins IL-4 and IL-13. IL-4 and IL-13 are two inflammatory cytokines believed to play a major role in type 2 inflammatory diseases such as atopic dermatitis, asthma, and eosinophilic esophagitis (EoE). In March 2017, the drug received FDA approval, becoming the first biologic agent for the treatment of moderate-to-severe atopic dermatitis. Additionally, it has been approved for use in patients with moderate-to-severe asthma (aged ≥12 years) and chronic rhinosinusitis with nasal polyps (adults).

Sanofi and Regeneron are also developing Dupixent for the treatment of diseases caused by allergies and other type 2 inflammatory conditions, including pediatric asthma (Phase 3), pediatric atopic dermatitis (Phase 2/3), chronic obstructive pulmonary disease (Phase 3), bullous pemphigoid (Phase 3), prurigo nodularis (Phase 3), chronic spontaneous urticaria (Phase 3), and food and environmental allergies (Phase 2).

Reference:

Dupixent® (dupilumab) Eosinophilic Esophagitis Trial Meets Both Co-Primary Endpoints