TEL-AVIV, Israel and RALEIGH, N.C., Oct. 11, 2019 (GLOBE NEWSWIRE) — RedHill Biopharma Ltd. (Nasdaq: RDHL) (Tel-Aviv Stock Exchange: RDHL) (“RedHill” or the “Company”), a specialty biopharmaceutical company primarily focused on the development and commercialization of clinical late-stage, proprietary drugs for the treatment of gastrointestinal diseases, today announced full Week 52 results for all subjects in the previously announced positive Phase 3 randomized, controlled study of RHB-104 in Crohn’s disease (the “MAP US study”) and supportive top-line results from the open-label extension Phase 3 study (the “MAP US2 study”).
The full Week 52 results of blinded treatment in the MAP US Phase 3 study with RHB-104 were consistent with the previously reported positive outcomes of the study. The study continued to meet its primary endpoint of clinical remission (CDAI < 150) at week 26 (36.7% vs. 22.4%, p=0.0048), key secondary endpoints of maintenance of remission at weeks 16 and 52 (25.9% vs. 12.1%, p=0.0016) and, notably, durable clinical remission on all visits, week 16 through 52 (18.7% vs. 8.5%, p=0.0077, 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 recently received and shared with FDA, 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 continues to analyze the data from the RHB-104 studies, including QT prolongation findings and various pharmacokinetic and pharmacodynamic models and, as previously announced, intends to meet with the FDA again in the coming months to discuss the RHB-104 program, including these data.
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 (Crohn’s Disease Active Index (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 top-line results from the MAP US2 study demonstrated 27.8% clinical remission with RHB-104 at week 16 and 22.2% remission at week 521. 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 top-line results and subsequent analyses were provided to RedHill by an independent third party following an 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, and completion of the Clinical Study Report (CSR).
The clinical studies with RHB-104 are registered on www.clinicaltrials.gov, a web-based service of the U.S. National Institute of Health, that provides access to information on publicly and privately-supported clinical studies.
RHB-104 is a proprietary, orally administered antibiotic combination therapy, with intracellular, antimycobacterial and anti-inflammatory properties. The randomized, double-blind, placebo-controlled, first Phase 3 study with RHB-104 in Crohn’s disease (the MAP US study) successfully met both its primary endpoint and key secondary endpoints and presented the benefit of RHB-104 as an add-on therapy to standard-of-care treatments for Crohn’s disease, including anti-TNF agents. The Company also reported supportive top-line results from an open-label extension Phase 3 study (MAP US2) evaluating the safety and efficacy of RHB–104 in subjects with persistent active Crohn’s disease after 26 weeks of blinded study therapy in MAP US. RHB-104 was developed based on the hypothesis that Crohn’s disease is caused by Mycobacterium avium subspecies paratuberculosis (MAP) infection in susceptible patients. The development of RHB-104 is consistent with the growing awareness of the possibility that a bacterially-induced dysregulated immune system may contribute to the pathogenesis of various autoimmune diseases of unknown etiology.
About RedHill Biopharma Ltd.
RedHill Biopharma Ltd. (Nasdaq: RDHL) (Tel-Aviv Stock Exchange: RDHL) is a specialty biopharmaceutical company, primarily focused on the development and commercialization of clinical late-stage, proprietary drugs for the treatment of gastrointestinal diseases. RedHill commercializes and promotes several gastrointestinal products in the U.S.: Donnatal® – a prescription oral adjunctive drug used in the treatment of IBS and acute enterocolitis; EnteraGam® – a medical food intended for the dietary management, under medical supervision, of chronic diarrhea and loose stools and Mytesi® – an anti-diarrheal drug indicated for the symptomatic relief of non-infectious diarrhea in adult patients with HIV/AIDS on antiretroviral therapy. RedHill’s key clinical late-stage development programs include: (i) RHB-105 (Talicia®) for the treatment and eradication of Helicobacter pylori infection with a U.S. NDA submitted and accepted for priority review with a target PDUFA action date of November 2, 2019; (ii) RHB-104, with positive top-line results from a first Phase 3 study for Crohn’s disease; (iii) RHB-204, with a planned pivotal Phase 3 study for pulmonary nontuberculous mycobacteria (NTM) infections; (iv) RHB-102 (Bekinda®), with positive results from a Phase 3 study for acute gastroenteritis and gastritis and positive results from a Phase 2 study for IBS-D; (v) Yeliva® (ABC294640), a first–in–class SK2 selective inhibitor, targeting multiple oncology, inflammatory and gastrointestinal indications, with an ongoing Phase 2a study for cholangiocarcinoma; (vi) RHB–106, an encapsulated bowel preparation licensed to Salix Pharmaceuticals, Ltd. and (vii) RHB-107, a Phase 2-stage first-in-class, serine protease inhibitor, targeting cancer and inflammatory gastrointestinal diseases. More information about the Company is available at: www.redhillbio.com.