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LAS VEGAS -- An investigational biologic drug targeting interleukin-13 was effective against eosinophilic esophagitis (EoE) at two doses as compared to placebo in a phase II trial, a researcher reported here.
In the randomized, placebo-controlled trial, the monoclonal antibody called RPC4046 at doses of 180 and 360 mg led to reductions from baseline in eosinophil counts of 94.8 and 99.9 cells per high power field (HPF), respectively, after 16 weeks, compared to a reduction of just 4.4 cells/HPF with placebo, reported, of the University of North Carolina in Chapel Hill.
Endoscopic features -- measured by total mean EoE Endoscopic Reference Score (EREFS) scores -- also manifested significant improvements with the drug. Reductions of 4.2 and 4.8 points were seen at the low and high doses, respectively, versus a 0.9-point decline in the placebo group (P<0.0004 vs placebo).
Global assessment of disease severity also showed a significant advantage for RPC4046 at the high but not the low dose, Dellon told attendees at the . He said an open-label extension of the trial is now underway.
"There's a huge need for new treatments for EoE," Dellon told ľֱ, noting that more than one-third of patients don't respond to current treatments.
Drug developer Celgene said RPC4046 binds to both the alpha-1 and alpha-2 subunits of the IL-13 receptor. This pathway has been considered a therapeutic target in asthma as well, although trial results with another biologic drug in that indication .
The so-called HEROES study randomized 99 patients into the three study groups, with 90 finishing across sites in the U.S., Canada and Switzerland. The average participant was a white male in his mid-to-late 30's, Dellon said, matching common EoE characteristics. The study was open to adults 65 and younger with histologic evidence or clinical symptoms of EoE. Patients with primary causes of esophageal eosinophilia other than EoE were excluded.
Participants received an IV dose on the trial's first day, followed by weekly subcutaneous doses. A central blinded pathologist read esophageal biopsies conducted at baseline and again at week 16 to assess change in mean eosinophil count, which was the study's primary endpoint. Secondary endpoints included symptom and endoscopic improvements, and Global Assessment of Disease Severity. Researchers also assessed safety.
Rates of overall adverse events were higher (85.3%) among high-dose patients versus placebo (64.7%) and low-dose (64.5%), however. The most frequent adverse events included headache, upper respiratory infection and arthralgia. Three serious adverse events were documented, Dellon said, including two hospitalizations.
The 52-week open-label phase of will seek primarily to measure safety and longer-term efficacy, Dellon said, and results should be available within the next several months.
Disclosures
Celgene funded the study.
Dellon reported relationships with Celgene, Adare, Miraca, Banner, Receptos, Regeneron, Roche, and Shire. Some co-investigators were Celgene employees. Other investigators reported relationships with a variety of commercial entities.