LAS VEGAS — A novel interleukin-13 inhibitor improved esophageal eosinophilic inflammation and endoscopic appearance in patients with eosinophilic esophagitis, according to results from the multicenter phase 2 HEROES study presented at ACG 2016.
“Interleukin-13 is a Th2 cytokine involved in allergic inflammation and fibrosis pathways and is heavily involved in EoE pathogenesis. For example, IL-13 is overexpressed in the esophageal tissue in EoE patients, it induces genes that overlap with the EoE transcriptome, and it influences the expression of a number of mediators in EoE.” Evan S. Dellon, MD, MPH, associate professor of medicine and epidemiology at the Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, said during his presentation.
Evan S. Dellon
“RPC4046 [Receptos] is a recombinant humanized monoclonal antibody highly selected for IL-13,” he said. “It inhibits binding of IL-13 to both of the IL-13 receptor types. It’s administered in a weekly subcutaneous injection and has not previously been studied in EoE.”
Dellon and colleagues randomly assigned EoE patients to receive placebo (n = 34) or one of two doses of RPC4046: 180 mg (n = 31) or 360 mg (n = 34). Patients received weekly subcutaneous doses, and 90 of them completed the 16-week double blind study period. Change in mean eosinophil count in esophageal biopsies obtained at baseline and week 16 served as the primary endpoint.
Mean eosinophil counts dropped significantly for both dose groups compared with placebo (P < .0001 for both). In addition, endoscopic improvements were seen in both RPC4046 dose groups compared with placebo (P < .0004 for both).
Daily symptom diaries showed a non-significant but strong trend toward improved dysphagia symptoms in the high dose group vs. placebo, and when this analysis was restricted to steroid-refractory patients, this improvement became significant. The Subjects Global Assessment of Disease Severity was also significantly improved in the higher dose group vs. placebo (P = .0107).
Adverse events occurred in 85.3% of the high dose group, 64.5% of the low dose group and 64.7% of the placebo group, the most common of which were headache, upper respiratory infection and arthralgia. Site injection reactions also occurred, most often in the high dose arm, Dellon said.
“RPC4046 treatment at both dose levels resulted in a significant reduction in the esophageal eosinophil count and improvement of endoscopic features of EoE,” Dellon concluded. “The 360 mg higher dose resulted in improvement in dysphagia symptoms with the greatest treatment effect in the steroid refractory group. The safety profile appeared to be favorable ... therefore, the efficacy and safety data from this study support the continued development of RPC4046 in EoE.”
An open-label extension study is ongoing, Dellon noted. – by Adam Leitenberger
Dellon E, et al. Abstract #19. Presented at: American College of Gastroenterology Annual Scientific Meeting; Oct. 17-19, 2016; Las Vegas, NV.
Disclosures: Dellon reports consulting for Adare, Banner, Receptos, Regeneron and Roche, and grants/research support from Meritage, Miraca Life Sciences, Receptos, Regeneron and Shire.