Regeneron Pharmaceuticals, Inc. and Sanofi presented results from the REMODEL Phase 4 trial demonstrating that Dupixent (dupilumab) showed significant and clinically meaningful improvements in both esophageal distensibility (a measure of esophageal function) as well as disease-related structural changes to the esophagus compared to placebo in adults with eosinophilic esophagitis (EoE) at week 24. The results reinforce the previously established ability of Dupixent to address underlying inflammation and symptoms of this disease; Dupixent was the first and is still the only biologic and leading treatment indicated for EoE. EoE is a chronic, progressive inflammatory disease associated with type 2 inflammation that damages the esophagus and prevents it from working properly.
In cases where EoE causes the esophagus to narrow, and the esophagus can no longer distend to support normal swallowing, forced and potentially painful dilation (physical expansion) of the esophagus may be needed. In severe cases, a feeding tube was historically the only available option to ensure proper caloric intake and adequate nutrition. Dupixent has dramatically changed the standard of care for this disease, improving quality of life for many patients.
In the REMODEL Phase 4 trial, 69 adults with EoE were treated with Dupixent 300 mg (n=46) every week or placebo (n=23). At week 24, the results for Dupixent compared to placebo were: Improved esophageal distensibility (a measure of esophageal function): 1.28 mm improvement in esophageal distensibility plateau from baseline compared to -0.01 mm (1.30 mm placebo-corrected improvement); Reduced disease-related structural changes to the esophagus: 4.89-point reduction from baseline in abnormal endoscopic findings, as assessed by EREFS (a scale ranging from 0-18), evaluating a combination of esophageal edema (swelling), rings (bands of scar tissue that narrow the esophagus), exudates (white plaques indicative of inflammation), furrows (vertical grooves indicative of damaged lining) and strictures (narrowing), compared to 0.07-point increase (4.96-point placebo-corrected reduction); Improved histological findings: 0.89-point and 0.80-point reductions from baseline in disease severity and extent, respectively, as assessed by the EoE-HSS grade and stage scores (both scales ranging from 0-3), measuring changes in eight cellular and tissue features of biopsy specimens at the microscopic level, compared to 0.18-point and 0.14-point reductions, respectively (0.71-point and 0.65-point placebo-corrected reductions, respectively); Increased histological remission: 59% of patients achieved peak esophageal intraepithelial counts of =6 eosinophils per high-power field (eos/hpf) compared to 4%. The safety results from the REMODEL trial were generally consistent with the known safety profile of Dupixent in EoE.
The overall rates of adverse events (AEs) were 62% for Dupixent and 48% for placebo. AEs more commonly observed with Dupixent than placebo included injection site pain (9% vs. 4%) and headache (9% vs.
4%). There were no serious AEs in either treatment group. The ongoing REMODEL Phase 4, randomized, double-blind, placebo-controlled trial is evaluating the impact of Dupixent on esophageal remodeling and function in adults with EoE.
During the 24-week, double-blind treatment period, all patients received Dupixent 300 mg every week or placebo. After week 24, patients entered an open-label treatment period and could either continue Dupixent or switch from placebo to Dupixent through week 128. The primary endpoint assessed change from baseline at week 24 in esophageal distensibility plateau as measured by endoluminal functional lumen imaging probe (EndoFLIP), an innovative approach to assess esophageal function based on scarring and narrowing.
Further assessments of esophageal distensibility are planned at week 76 and week 128 during the open-label treatment period. Esophageal distensibility plateau is reported in millimeters and represents how the esophagus expands in response to a small balloon being inflated at multiple points inside the esophagus. The distensibility plateau is the maximum esophageal diameter achieved at the narrowest point of the esophagus when further increases in balloon pressure do not meaningfully increase diameter.
Higher numbers represent better esophageal function, and lower numbers represent worse function. Secondary endpoints assessed at week 24 included: Percent change from baseline in esophageal distensibility plateau as measured by EndoFLIP, the key secondary endpoint; Change from baseline in EoE Endoscopic Reference Score (EoE-EREFS) on a 0-18 scale; Change from baseline in EoE Histology Scoring System (EoE-HSS) grade and stage scores, which measure changes in eight cellular and tissue features on 0-3 scales, respectively; Proportion of patients achieving histological disease remission (peak esophageal intraepithelial eosinophil count of =6 eosinophils [eos]/high power field [hpf]); Proportion of patients achieving the diagnostic threshold for EoE (peak esophageal intraepithelial eosinophil count of VelocImmune technology, is a fully human monoclonal antibody that inhibits the signaling of the interleukin-4 (IL-4) and interleukin-13 (IL-13) pathways and is not an immunosuppressant.
