RedHill Biopharma initiates phase II study of BEKINDA for irritable bowel syndrome

RedHill Biopharma Ltd. (NASDAQ; RDHL) (TASE: RDHL) (“RedHill” or the “Company”), a biopharmaceutical company primarily focused on development and commercialization of late clinical-stage, proprietary, orally-administered, small molecule drugs for inflammatory and gastrointestinal diseases, including cancer, today announced that it has initiated a randomized, double-blind, 2-arm parallel group Phase II clinical study in the U.S. evaluating the safety and efficacy of BEKINDA™ 12 mg in patients with diarrhea-predominant irritable bowel syndrome (IBS-D).

“We are excited to initiate this study of BEKINDA™ for IBS-D, a debilitating disorder affecting millions of people worldwide with few approved therapies and a significant unmet medical need,” said Gilead Raday, RedHill’s Chief Operating Officer. “This study follows publications demonstrating that ondansetron, the active ingredient in BEKINDA™, may be an effective and safe treatment for IBS-D. We also continue to advance the Phase III GUARD study of BEKINDA™ for acute gastroenteritis and gastritis, currently ongoing in the U.S., with top-line results expected during the second half of this year.”

BEKINDA™ is a proprietary, extended-release, once-daily oral pill formulation of the antiemetic drug ondansetron, targeting multiple gastrointestinal indications. RedHill is pursuing clinical studies with two dose strengths of BEKINDA™, a 24 mg dose and a 12 mg dose. 5-HT3 antagonists such as ondansetron, the active pharmaceutical ingredient in BEKINDA™, have been shown to slow intestinal transit time in humans(1). Alosetron (Lotronex®), a 5-HT3 antagonist of the same class of drugs as ondansetron, the active ingredient in BEKINDA™, has been approved for the treatment of women with severe chronic IBS-D but is under a restricted prescribing (REMS) program due to potential severe side effects(2). Ondansetron, approved by the U.S. FDA as an oncology support antiemetic, has demonstrated activity in IBS-D in preliminary studies(3) and, in light of its good safety profile, RedHill believes that BEKINDA™, if approved, has the potential to be a preferred once-daily treatment for a broad segment of patients suffering from IBS-D.

The randomized, double-blind, 2-arm parallel group Phase II clinical study is designed to evaluate the safety and efficacy of BEKINDA™ 12 mg in patients suffering from IBS-D. The study is expected to be conducted in 12 clinical sites in the U.S. and to enroll 120 patients who will be randomized 60:40 to receive either BEKINDA™ 12 mg or a placebo, once daily, for a period of eight weeks. The primary endpoint for the study is the proportion of patients in each treatment group with response in stool consistency as compared to baseline, per FDA guidance definition. Secondary endpoints include the proportion of patients in each treatment group who are pain responders and the proportion of patients in each treatment group who are responders to the combined endpoints of stool consistency and pain, per FDA guidance definition.

Irritable bowel syndrome (IBS) is a chronic multifactorial disorder characterized by recurrent abdominal pain or discomfort associated with altered bowel function. Diarrhea-predominant irritable bowel syndrome (IBS-D) is the most common subtype of IBS in the U.S.(4) Certain factors that may alter gastrointestinal function can contribute to IBS symptoms, including stress, prior gastroenteritis and changes in the gut microbiome. However, the etiology of IBS is not well-understood and the underlying cause of IBS in many cases remains unknown. IBS negatively impacts patients’ health-related quality of life and can affect patients physically, emotionally, socially and economically.

IBS is one of the most common GI disorders; it is estimated that at least 30 million Americans suffer from IBS(5), of which over 50% are cases of IBS-D4. The U.S. potential market for IBS-D treatments is estimated to exceed $1.3 billion by 2020(6)

About BEKINDA™ (RHB-102)

BEKINDA™ is a patent-protected, extended-release (24 hours) oral pill formulation of ondansetron. A Phase III clinical study of BEKINDA™ for acute gastroenteritis and gastritis (the GUARD study) is ongoing in the U.S., with top-line results expected in the second half of 2016. A Phase II study has been initiated with BEKINDA™ for the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D). RedHill is also pursuing marketing approval of BEKINDA™ in Europe for the prevention of chemotherapy and radiotherapy-induced nausea and vomiting (CINV and RINV, respectively), pending additional feedback from EU member states as to whether additional clinical and CMC work is required.

About RedHill Biopharma Ltd.

RedHill Biopharma Ltd. (NASDAQ/TASE: RDHL) is a biopharmaceutical company headquartered in Israel, primarily focused on the development and commercialization of late clinical-stage, proprietary, orally-administered, small molecule drugs for the treatment of inflammatory and gastrointestinal diseases, including cancer. RedHill’s current pipeline of proprietary products includes: (i) RHB-105 - an oral combination therapy for the treatment of Helicobacter pylori infection with successful results from a first Phase III study; (ii) RHB-104 - an oral combination therapy for the treatment of Crohn's disease with an ongoing first Phase III study and an ongoing proof-of-concept Phase IIa study for multiple sclerosis; (iii) BEKINDA™ (RHB-102) - a once-daily oral pill formulation of ondansetron with an ongoing Phase III study in the U.S. for acute gastroenteritis and gastritis and a Phase II study for IBS-D; (iv) RHB-106 - an encapsulated bowel preparation licensed to Salix Pharmaceuticals, Ltd.; (v) YELIVA™ (ABC294640) - an orally-administered first-in-class SK2 selective inhibitor targeting multiple oncology, inflammatory and gastrointestinal indications with a Phase I/II study initiated for refractory/relapsed diffuse large B-cell lymphoma (DLBCL); (vi) MESUPRON® - a Phase II-stage first-in-class uPA inhibitor, administered by oral capsule, targeting gastrointestinal and other solid tumors; (vii) RP101 - currently subject to an option-to-acquire by RedHill, RP101 is a Phase II-stage first-in-class Hsp27 inhibitor, administered by oral tablet, targeting pancreatic and other gastrointestinal cancers; (viii) RIZAPORT™ (RHB-103) - an oral thin film formulation of rizatriptan for acute migraines, with a U.S. NDA currently under discussion with the FDA and marketing authorization received in Germany in October 2015; and (ix) RHB-101 - a once-daily oral pill formulation of the cardio drug carvedilol.

1. Garsed K. et al, A randomised trial of ondansetron for the treatment of irritable bowel syndrome with diarrhoea, Gut (2014), 63(10): 1617-25.
2. www.fda.gov, post market drug safety information for patients and providers.
3. Steadman CJ et al, Selective 5-hydroxytryptamine type 3 receptor antagonism with ondansetron as treatment for diarrhea-predominant irritable bowel syndrome: a pilot study, Mayo Clin Proc (1992), 67(8):732-8; Clayton NM et al, The pharmacological properties of the novel selective 5-HT3 receptor antagonist, alosetron, and its effects on normal and perturbed small intestinal transit in the fasted rat, Neurogastroenterol (1999), 11: 207-217; Garsed K. et al, A randomised trial of ondansetron for the treatment of irritable bowel syndrome with diarrhoea, Gut (2014), 63(10): 1617-25.
4. GlobalData PharmaPoint: Irritable Bowel Syndrome - Global Drug Forecast and Market Analysis to 2023.
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6. EvaluatePharma - Irritable bowel syndrome Indication Profile