An experimental monoclonal antibody against interleukin-13, RPC4046, appears to be well tolerated in patients with eosinophilic esophagitis (EoE) and yielded improvement and/or maintenance of EoE disease activity relative to baseline measures, according to the results of a study published in Clinical Gastroenterology and Hepatology.
Following up on a study demonstrating the short-term efficacy of RPC4046, Dellon and colleagues investigated the long-term efficacy and safety of RPC4046 in an open-label, long-term extension (LTE) study in adults with EoE (Clinical Trials.gov Identifier: NCT02098473).
The international, multicenter study (28 centers in 3 countries) enrolled patients from September 2014 to January 2017. Data were stratified according to double-blind dose group. Study outcomes included esophageal eosinophil counts, EoE endoscopic reference score, EoE histologic scoring system score, symptom-based EoE activity index score, and safety.
Patients who completed the short-term portion of the study (RPC4046 180 mg or 360 mg/wk vs placebo) were able to continue in the LTE portion of the study for 52 weeks (open-label RPC4046 360 mg/wk). Overall, 90 patients completed the first portion, while 66 of 86 patients who enrolled in the LTE portion completed the study.
After starting RPC4046, the outcomes for patients who originally received placebo (esophageal eosinophil mean and peak counts, total EoE endoscopic reference scores, and EoE histologic scoring system grade and stage scores) were not significantly different at week 12, and most patients maintained their responses through week 52.
Upon starting the LTE, patients who originally received placebo had peak esophageal eosinophil counts that were 3 times higher than patients who had been receiving active treatment (either dose).
For patients who originally received placebo and started RPC4046 in the LTE, the proportion of patients with symptom remission increased from 14% at study entry to 67% at week 52.
For patients who originally received RPC4046 (either dose) and continued on the higher dose in the LTE, the proportion of patients with symptom remission increased from 30% at study entry to 54% at week 52.
During the short-term portion of the study, 28 patients did not have a histologic response to RPC4046. However, during the LTE, a response was reported in 10 of those patients (36%).
Reasons for study discontinuation during the LTE were withdrawal of consent (n=7), adverse events (n=6), nonadherence (n=3), investigator decision (n=1), pregnancy (n=1) and other (n=2). Overall, the most common adverse events reported were upper respiratory tract infection (21%), nasopharyngitis (14%), oropharyngeal pain (12%), sinusitis (12%), and headache (11%).
Study limitations included that approximately 25% (20/86) of patients did not complete the full 52 weeks of the LTE, the LTE portion of the study was not blinded, and the ability to conduct statistical comparisons was limited. The authors noted that patients were aware that they were receiving the drug; thus, symptom data should be interpreted with caution.
“The safety and immunogenicity data suggest that this dose was well-tolerated, with no new safety signals identified with longer-term treatment,” wrote the authors.
Disclosures: The referenced study was sponsored by Celgene Corporation. Some authors have declared affiliations with the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Dellon ES, Collins MH, Rothenberg ME, et al. Long-term efficacy and tolerability of RPC4046 in an open-label extension trial of patients with eosinophilic esophagitis [published online March 12, 2020]. Clin Gastroenterol Hepatol. doi:10.1016/j.cgh.2020.03.036