Crohns Disease Treatment, RHB-104, Yields Positive Results in Phase 3 Trial

Top-line results from RedHill Biopharma Ltd.’s phase 3 trial assessing RHB-104 as a treatment for Crohn’s disease show that the orally-administered antibiotic combination therapy met both its primary and secondary endpoints with an early remission rate achieved at week 26 and consistent benefit maintained.

“The robust results of this study demonstrate that RHB-104 could become a leading therapeutic option in Crohn’s disease and bring hope to patients worldwide,” RedHill’s medical director Ira Kalfus, MD, said in a recent statement. “This is the first global, double-blind, placebo-controlled study that demonstrates the efficacy of anti-MAP therapy in Crohn’s disease. The availability of antibiotic therapy for treating Crohn’s disease could be transformative.”

RHB-104 is a proprietary antibiotic combination therapy in oral capsule formulation that has potent intracellular, antimycobacterial, and anti-inflammatory properties; it is grounded in the hypothesis that Crohn’s disease is caused by Mycobacterium avium subspecies paratuberculosis (MAP) infection in susceptible patients, according to RedHill Bio.

In the study, 330 patients with Crohn’s disease were divided into 2 treatment arms, experimental or placebo, and administered 5 RHB-104 capsules or placebo orally twice-daily (BID). Remission at week 26 was the primary endpoint of the study, defined as the Crohn's Disease Activity Index (CDAI) score of less than 150.

Secondary outcome measures included a response at week 26 as measured by a reduction of CDAI score by a minimum of 100 points in the timeframe of 26 weeks, the time to remission response as measured by the time (weeks after randomization) that a participant first records a state of remission or response in the timeframe of 52 weeks, the duration of remission and response as measured by the time that a subject is in a state of remission or response in the timeframe of 52 weeks, and the maintenance of remission as measured by remission in a subject from week 26 through week 52 in the timeframe of 52 weeks.

Patients who were administered RHB-104 achieved a statistically significant greater response at week 26 (defined as a decrease of ≥100 in CDAI from baseline) compared with those who were treated with placebo (44% vs. 31%, p= 0.028). Patients administered RHB-104 also experienced a statistically significant benefit in achieving early remission defined as remission at week 16 (42% vs. 29%, p= 0.019).

A statistically significant benefit in durable remission over weeks 16 to 52, which was defined as continuous remission throughout the period, (18% vs. 9%, p= 0.038), was also experienced by patients treated with RHB-104 and demonstrated an improvement of 100% over placebo. Remission in the RHB-104 arm also continued to be favorable to placebo (27% vs. 20%, p= 0.155) at week 52 of treatment.

An analysis of maintenance of remission at week 52 in subjects recorded to be in remission at week 16 also exhibited a statistically significant benefit with RHB-104 over placebo (25% vs. 12%, p= 0.007).

RHB-104 was found to be safe and well tolerated overall. Both the active and placebo treatment groups experienced similarly low rates of serious adverse events and treatment emergent adverse events leading to study drug discontinuation. Consequently, RHB-104 was granted a positive safety profile.

RedHill will continue assessing additional exploratory endpoints as data becomes available, including mucosal healing, MAP status, quality of life assessment, sub-population analyses, and pharmacokinetics. The coming months are anticipated to provide additional data.

“Further analysis of the data will potentially be used to identify and enrich the target population in future studies,” said Dror Ben-Asher, CEO of RedHill Biopharma exclusively to Rare Disease Report. “During the coming months, we will also be meeting with key opinion leaders and the US Food and Drug Administration to present the data package and discuss the development path to potential approval and will continue discussions with potential partners for RHB-104. We also plan to submit a late-breaking abstract to the American College of Gastroenterology Annual Scientific Meeting, which is in October 2018, and expect to present the results at additional conferences.”