Dupilumab was associated with clinical and anatomic improvements in patients with eosinophilic esophagitis, according to results from a pivotal phase 3 study.
Part A of the randomized, double-blind, placebo-controlled trial assessed the treatment effect of dupilumab in 81 patients aged ≥12 years with eosinophilic esophagitis, as determined by histological and patient-reported measures. Patients were randomized to receive either dupilumab 300mg weekly or placebo for 24 weeks. The co-primary end points were the proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤6 eosinophils per high-power field, and the absolute change in Dysphagia Questionnaire (DSQ) score, at 24 weeks.
Results showed that patients treated with dupilumab had a 60% reduction in their esophageal eosinophilic count to a normal range vs 5% for placebo (P <.0001), and a 69% reduction in disease symptoms, as measured by the DSQ score, vs 32% for placebo (P =.0002); dupilumab-treated patients experienced a 21.92 point improvement in DSQ score vs a 9.60 point improvement for placebo (P =.0004).
At 24 weeks, dupilumab was also associated with a 39% reduction in abnormal endoscopic findings (secondary end point) compared with 0.6% for placebo, as measured by the EoE Endoscopic Reference Score (-3.2 vs -0.3, respectively; P <.0001)
The safety profile of dupilumab was found to be similar to that seen in previous studies for approved indications. Compared with placebo, dupilumab had a higher frequency of injection site reactions (n=12 vs n=15) and upper respiratory tract infections (n=6 vs n=11). There was 1 treatment discontinuation in the dupilumab arm due to arthralgia.
Full detailed results from this trial will be presented at an upcoming medical meeting. Investigators are currently enrolling additional patients in Part B of the trial to assess dosing regimens, as well as Part C, a 28-week extended treatment period.
The Food and Drug Administration (FDA) previously granted Orphan Drug designation to dupilumab for eosinophilic esophagitis. “In the past, [eosinophilic esophagitis] was thought to be a disease caused by eosinophils, but other biologics that decrease eosinophils in the esophagus did not demonstrate consistent clinical or anatomical improvements,” said George D. Yancopoulos, MD, PhD, Co-Founder, President and Chief Scientific Officer of Regeneron. “These Dupixent results demonstrate [eosinophilic esophagitis] is caused by multiple aspects of type 2 inflammation, driven by interleukin-4 and interleukin-13.”
Dupilumab, an interleukin-4 receptor alpha antagonist, is currently approved under the brand name Dupixent® (Regeneron and Sanofi) for the treatment of atopic dermatitis, asthma and chronic rhinosinusitis with nasal polyposis.