TEL-AVIV, Israel and RALEIGH, N.C.—RedHill Biopharma Ltd. announced today the full Week 52 results for all subjects in the Phase 3 randomized, controlled study of RHB-104 in Crohn’s disease (MAP US study) and supportive topline results from the open-label extension Phase 3 study (MAP US2 study).
RHB-104 is a proprietary, orally administered antibiotic combination therapy with intracellular, antimycobacterial and anti-inflammatory properties. The therapy was developed based on the hypothesis that Crohn’s disease is caused by Mycobacterium avium subspecies paratuberculosis (MAP) infection in susceptible patients.
The full Week 52 results of blinded treatment in the MAP US Phase 3 study were consistent with the previously reported positive outcomes of the study. The study continued to meet its primary endpoint of clinical remission (Crohn’s Disease Activity Index [CDAI] < 150) at week 26 (36.7% vs. 22.4%), key secondary endpoints of maintenance of remission at weeks 16 and 52 (25.9% vs. 12.1%), and durable clinical remission on all visits for weeks 16 through 52 (18.7% vs. 8.5%) for RHB-104 vs. placebo, respectively.
In the analysis of the complete safety information for the study, a top-line electrocardiogram (ECG) monitoring report for the MAP US study demonstrated evidence of progressive prolongation of the QTcF interval across visits, with the largest placebo-corrected ΔQTcF (∆∆QTcF) of 30.6 ms at Week 52 of treatment with RHB-104. None of these QT abnormalities resulted in adverse cardiac events. Clofazimine, as well as clarithromycin (another active component of RHB-104), are known to be associated with QT prolongation.
RedHill will continue to analyze the data from the RHB-104 studies, including QT prolongation findings, and various pharmacokinetic and pharmacodynamic models. The company also plans to meet with the U.S. Food and Drug Administration (FDA) again in the coming months to discuss the development path toward potential approval of RHB-104.
The MAP US2 open-label extension Phase 3 study evaluated the safety and efficacy of RHB-104 in subjects from the MAP US study with persistent active Crohn’s disease (CDAI ≥ 150) after 26 weeks of blinded study therapy. A total of 54 subjects entered the open-label extension study and 30 subjects completed 52 weeks of treatment. Interim topline results from the MAP US2 study demonstrated 27.8% clinical remission with RHB-104 at week 16, and 22.2% remission at week 52.
Of the MAP US2 subjects who were previously randomized to the placebo arm (as an add-on to standard-of-care therapies) in the MAP US study and treated with RHB-104 for the first time in the MAP US2 study, 31.6% achieved remission at week 16 and 26.3% achieved remission at week 52. These results further support the potential clinical benefit of treatment with RHB-104 in Crohn’s disease patients.
RHB-104 was found to be generally safe and well tolerated. The incidence of treatment emergent adverse events, serious adverse events and reported adverse events leading to discontinuation in the MAP US2 study were lower than in the active arm of the MAP US study (77.8% vs. 87.3%, 7.4% vs. 18.7% and 9.3% vs. 21.1%, respectively). Similar trends were observed in MAP US2 subjects who received concomitant anti-TNFs, consistent with the safety of treatment with RHB-104 in combination with anti-TNF agents.
The topline results and subsequent analyses were provided to RedHill by an independent third party following independent analysis, and remain subject to completion of the independent review and analysis of the underlying data, including all safety, secondary and other outcome measures, as well as completion of the Clinical Study Report CSR.
RedHill Biopharma will be presenting the RHB-104 data at the upcoming American College of Gastroenterology 2019 Annual Scientific Meeting held later this month, October 25-30.
Back in June, RedHill received a Notice of Allowance from the U.S. Patent and Trademark Office (USPTO) for a new patent covering RHB-104 for Crohn’s disease and RHB-204 for Mycobacterium avium complex (MAC) disease, the most common cause of pulmonary nontuberculous mycobacteria (NTM) infections. Once granted, the patent is expected to be valid until at least 2029.
“We continue to build and strengthen our intellectual property portfolio covering both RHB-104 and RHB-204,” Danielle Abramson, Ph.D., RedHill’s vice president of Intellectual Property and Research, stated in a press release. “Once this new patent is granted, the robust patent portfolio for RHB-104 will include seven issued U.S. patents, three of which also protect RHB-204, as well as additional issued and pending patents worldwide.”
The company plans to initiate a pivotal Phase 3 study with RHB-204 for the treatment of pulmonary NTM infections in the second half of 2019, subject to completion of the ongoing supportive non-clinical program and additional input from the FDA. The study is intended to assess the efficacy and safety of RHB-204 and potentially support its approval as a stand-alone, first-line treatment for pulmonary NTM infections caused by MAC.