RedHill Biopharma announces successful Phase III

RedHill Biopharma Ltd. (Tel-Aviv Stock Exchange: RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company primarily focused on late clinical-stage development and commercialization of proprietary, orally-administered, small molecule drugs for gastrointestinal and inflammatory diseases and cancer, announced positive top-line results from the Phase III GUARD study with BEKINDA (RHB-102)(1) 24 mg for acute gastroenteritis and gastritis. The study successfully met its primary endpoint of efficacy in treatment of acute gastroenteritis. BEKINDA was found to be safe and well tolerated in this indication.

The randomized, double-blind, placebo-controlled Phase III GUARD study evaluated the efficacy and safety of BEKINDA 24 mg in treating acute gastroenteritis and gastritis. 321 adults and children over the age of 12 were enrolled at 21 clinical sites in the U.S. and randomized in a 60:40 ratio to receive either BEKINDA 24 mg or placebo, respectively. The primary endpoint of the study was the proportion of patients without further vomiting, without rescue medication, and who were not given intravenous hydration from 30 minutes post first dose of the study drug until 24 hours post dose, compared to placebo.

Top-line results indicated that the Phase III GUARD study successfully met its primary endpoint in the Intent to Treat (ITT) population (p = 0.04), despite high positive outcome rate in the placebo arm. BEKINDA improved the efficacy outcome by 21%; 65.6% of BEKINDA treated patients as compared to 54.3% of placebo patients (p = 0.04; n=192 in the BEKINDA group and n=129 in the placebo group).  Correcting for a randomization error, the difference in effect is greater with 65.8% vs. 53.9% favoring BEKINDA vs. placebo in reaching the primary endpoint of the study (p = 0.03). In per-protocol (PP) analysis of patients who met all protocol entry criteria and for which the diagnosis of gastroenteritis was confirmed (n=177 in the BEKINDA group and n=122 in the placebo group), BEKINDA improved the efficacy outcome by 27%; 69.5% of patients in the BEKINDA group vs. 54.9% in the placebo group (p = 0.01). BEKINDA 24 mg was also shown to be safe and well-tolerated. Importantly, electrocardiogram results showed no adverse changes with treatment.

Robert A. Silverman, MD, MS, Emergency Medicine specialist at Northwell Health and Lead Investigator of the BEKINDA Phase III GUARD study, said: "The positive results of the Phase III GUARD study demonstrate that BEKINDA 24 mg is beneficial in the treatment of acute gastroenteritis and gastritis and can provide patients with 24 hours of relief. Gastroenteritis is a very common illness in the U.S., with approximately 179 million cases annually. If approved by FDA, BEKINDA may become the new standard of care helping us treat patients quickly and effectively in both the emergency and outpatient settings."

Terry F. Plasse, MD, RedHill’s Medical Director, added: "We are excited about the positive outcome of the Phase III GUARD study, which met its efficacy primary endpoint and demonstrated the safety and tolerability of BEKINDA 24 mg. Notably, when looking at results by initial severity of nausea, we see a treatment effect even in patients with very severe nausea at baseline, suggesting that the drug works regardless of the initial severity of gastroenteritis. We continue to analyze the data, with the final clinical study report expected in the third quarter of 2017. We look forward to presenting the data to the FDA and discussing the potential path for marketing approval of BEKINDA 24 mg in the U.S. and whether additional clinical studies are required prior to NDA filing. We are also expecting top-line Phase II results from the clinical study of BEKINDA 12 mg in diarrhea-predominant irritable bowel syndrome (IBS-D) in September 2017. I would like to thank the patients, investigators, clinical staff and service providers who participated in the GUARD study and commend the RedHill team for achieving this important milestone."

BEKINDA is a proprietary, bimodal extended-release, once-daily oral pill formulation of the antiemetic drug ondansetron, targeting several gastrointestinal indications. BEKINDA 24 mg is intended to provide patients with relief from nausea and vomiting symptoms for a full 24-hour period with a single oral tablet. If approved for marketing by the FDA, BEKINDA 24 mg could become the first 5-HT3 antiemetic drug in the U.S. indicated for the treatment of acute gastroenteritis and gastritis.

RedHill will continue to analyze the GUARD Phase III study top-line data, including secondary endpoints, and plans to meet with the FDA to present the data and discuss the clinical and regulatory path towards potential marketing approval of BEKINDA 24 mg in the U.S. Additional clinical studies may be required prior to potential submission of a New Drug Application (NDA).

The top-line results from the GUARD Phase III study 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), expected in the third quarter of 2017.

Acute gastroenteritis and gastritis are inflammations of the mucus membranes of the gastrointestinal tract leading to a combination of symptoms which include nausea, vomiting, diarrhea or abdominal pain. Acute gastroenteritis is a common infectious disease, with approximately 179 million cases annually in the U.S.(2) It is caused by many different infectious agents, most commonly by viral infections, accounting for up to 70% of cases(3). Noroviruses cause the most outbreaks of non-bacterial acute gastroenteritis in all age groups and often occur in epidemic outbreaks in schools, nursing homes and other group settings(3). Gastroenteritis and gastritis are major causes of emergency room visits, with up to 474,000 estimated hospitalizations annually in the U.S. alone(2). Oral rehydration is the preferred therapy in mild to moderate dehydration, whereas intravenous fluids are recommended in more severe cases(4). Adding ondansetron, the active ingredient in BEKINDA, to the standard intravenous rehydration therapy has shown to significantly reduce the amount of vomiting in children with gastroenteritis(5); however, to the best of RedHill’s knowledge, its efficacy in adult gastroenteritis patients has not been shown beneficial in a randomized clinical trial in the U.S.

Ondansetron is approved as an antiemetic in patients suffering from chemotherapy and radiotherapy-induced nausea and vomiting and from postoperative nausea and vomiting(6). BEKINDA may decrease the frequency of vomiting, improve the success and compliance of oral rehydration therapy and decrease the rate of intravenous therapy in patients suffering from gastroenteritis. BEKINDA is targeting a potential worldwide market estimated to exceed $650 million annually(3)