Date: 2015-09-08
Type of information: Results
phase: 3
Announcement: results
Company: RedHill Biopharma (Israel)
Product: RHB-105 (amoxicillin, rifabutin and omeprazole)
Action
mechanism: antibiotic/ proton pump inhibitor. RHB-105 is a new and proprietary fixed-dose combination therapy of two antibiotics (amoxicillin and rifabutin) and a proton pump inhibitor (omeprazole), in an all-in-one oral capsule, designed for the treatment of H. pylori bacterial infection - a major cause of chronic gastritis, peptic ulcer disease, gastric cancer and mucosa associated lymphoid tissue (MALT) lymphoma. The RHB-105 combination was originally developed by Professor Thomas Borody, a leading innovator of therapeutic approaches to gastrointestinal tract diseases, who developed the first approved triple therapy treatment for H. pylori associated with peptic ulcer disease. RHB-105 was designated by the FDA as a Qualified Infectious Disease Product (QIDP) under the Generating Antibiotic Incentives Now (GAIN) Act, which is intended to incentivize the development of new antibiotic drugs for the treatment of serious or life-threatening infections. The designation allows RedHill to benefit from Fast-Track development status for RHB-105, providing for an expedited development pathway, as well as Priority Review status, potentially leading to a shorter review time by the FDA of a New Drug Application (NDA), if filed. If approved, RHB-105 will also receive an additional five years of U.S. market exclusivity in addition to the standard exclusivity period, for a total of 8 years of market exclusivity.
Disease: Helictobacter pylori infection
Therapeutic area: Infectious diseases
Country: USA
Trial
details: The Phase III ERADICATE Hp clinical study is designed to evaluate the safety and efficacy of RHB-105 as a first-line treatment for confirmed Helicobacter pylori (H. pylori) bacterial infection, a major cause of chronic gastritis, peptic ulcer disease, gastric cancer and mucosa associated lymphoid tissue (MALT) lymphoma.
This randomized, double-blind, placebo-controlled, Phase III study is expected to enroll 90 non-investigated dyspepsia subjects with confirmed H. pylori infection in 8 clinical sites in the U.S. Subjects are randomized in a 2:1 ratio to receive four capsules three times daily of either RHB-105 or placebo for a period of 14 days, and are assessed for the study's primary endpoint of eradication of H. pylori infection 28 to 56 days after completion of treatment. (NCT01980095)
Latest
news: * On September 8, 2015, RedHill Biopharma , an Israeli biopharmaceutical company primarily focused on late clinical-stage, proprietary, orally-administered, small molecule drugs for inflammatory and gastrointestinal diseases, including cancer, announced additional supportive data from the first Phase III study with RHB-105 for eradication of H. pylori (the ERADICATE Hp Study). Results from the subsequent open-label treatment of patients in the placebo arm with standard-of-care (SoC) therapy for persistent H. pylori infection demonstrated a 63% eradication rate with SoC, compared to the previously reported 89.4% eradication rate demonstrated in the RHB-105 arm of the controlled study. These results further support the potential superior efficacy of RHB-105 over SoC and validate the use of the historical SoC efficacy threshold of 70% implemented in the ERADICATE Hp study as the control for the study’s primary endpoint. RedHill announced in June 2015 positive top-line results from the ERADICATE Hp Phase III study for the treatment of H. pylori bacterial infection. The top-line results demonstrated 89.4% efficacy in eradicating H. pylori infection with RHB-105 (see below). Completion of the clinical study report (CSR) is expected in the fourth quarter of 2015. RedHill recently entered into an agreement with Recipharm, a leading CMO (Contract Manufacturing Organization) for the manufacture of RHB-105. Under the terms of the agreement, Recipharm will be responsible for manufacturing RHB-105 for the planned second Phase III study and for future potential commercial supply of RHB-105. * On June 15, 2015, RedHill Biopharma announced positive top-line results from its Phase III study with RHB-105 for the treatment of Helicobacter pylori (H. pylori) bacterial infection. The randomized, placebo-controlled, ERADICATE Hp Phase III study was designed to evaluate the safety and efficacy of RHB-105 as a first-line treatment for confirmedH. pylori infection. A total of 118 dyspepsia patients with confirmed H. pylori infection were enrolled and treated in the ERADICATE Hp study, which was conducted in 13 clinical sites in the U.S. Top-line results from the study demonstrated 89.4% efficacy in eradicating H. pylori infection with RHB-105. The ERADICATE Hp first Phase III study successfully met its primary endpoint of superiority over historical standard of care efficacy levels of 70%, with high statistical significance (p <0.001). No serious adverse events, new or unexpected safety issues were noted in the study. * On April 27, 2015, RedHill Biopharma announced that the last patient has been enrolled in the first Phase III clinical study of RHB-105 for the treatment of Helicobacter pylori infection. Top-line results from the Phase III study are expected in mid-end June 2015. The randomized, placebo-controlled, Phase III study (the ERADICATE Hp study) is intended to evaluate the safety and efficacy of RHB-105 as a first-line treatment for confirmed H. pylori bacterial infection. The ERADICATE Hp Phase III study is planned to be followed, if successful, by a second Phase III study, and additional studies may be required subject to FDA feedback. A total of 118 non-investigated dyspepsia patients with confirmed H. pylori infection were enrolled in the study, which was conducted in 13 clinical sites in the U.S. Subjects were randomized in a 2:1 ratio to receive either RHB-105 or placebo for a period of 14 days, and assessed for eradication of H. pylori infection 28 to 35 days after completion of treatment. The primary endpoint of the study is to show superiority in eradication of H. pylori infection over historical standard of care efficacy levels of 70% effectiveness. With RHB-105, RedHill is pursuing an indication of first line treatment of H. pylori infection regardless of ulcer status, a significantly broader indication than current standard treatments for H. pylori, which are typically limited and indicated to treat patients with an active or recent history of ulcers. If approved, RHB-105 may be the first H. pylori eradication therapy to target this broader indication, which would significantly expand the potential patient population on the label for this drug. In November 2014, the FDA designated RHB-105 as a Qualified Infectious Disease Product (QIDP) under the FDA's Generating Antibiotic Incentives Now (GAIN) Act, which is intended to encourage new antibiotic drugs for the treatment of serious or life-threatening infections. The designation allows RedHill to benefit from Fast-Track development status for RHB-105, providing for an expedited development pathway as well as Priority Review status, potentially leading to a shorter review time by the FDA of a New Drug Application (NDA), if filed. If approved, RHB-105 will also receive an additional five years of U.S. market exclusivity on top of the standard exclusivity period, for a total of 8 years of market exclusivity. * On August 27, 2014, RedHill Biopharma provided an update on the ongoing RHB-105 Phase III ERADICATE Hp study. In order to enhance statistical powering and expedite recruitment, RedHill is expanding the study to include, respectively, additional subjects and clinical sites. The Company further announced that, based on prior discussions, the FDA has authorized RedHill to pursue a new, distinct and broader indication with RHB-105, a proprietary fixed-dose combination therapy of two antibiotics and a proton pump inhibitor (PPI) in an all-in-one oral capsule for the first line treatment of Helicobacter pylori (H. pylori) infection. The ongoing Phase III ERADICATE Hp study follows a successful Phase II study in Australia with 130 subjects, as well as a successful PK study conducted in 2013. * On December 17, 2013, RedHill Biopharma has announced that the first patients have been dosed in the Phase III ERADICATE Hp clinical study in the U.S. Seven of the eight clinical sites in the U.S. have commenced enrollment of patients for the ERADICATE Hp study, and the last site is expected to commence enrollment shortly. RedHill Biopharma expects data from this study to be available by the third quarter of 2014.
The top-line results from the RHB-105 Phase III study, demonstrating achievement of primary endpoint, 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 2015. The ERADICATE Hp Phase III study is planned to be followed by a second Phase III study and additional studies may be required, subject to FDA feedback.
Ira Kalfus, M.D., RedHill's Medical Director, added: "On the basis of the clear success of the ERADICATE Hp study, and the Fast-Track designation of RHB-105, we look forward to meeting with FDA to discuss the clinical and regulatory path towards marketing approval in the U.S. No new or unexpected safety issues were identified. Efficacy and safety data from this study will be submitted for presentation at an upcoming medical meeting.
As part of an amendment to the ongoing RHB-105 Phase III ERADICATE Hp study protocol, currently being reviewed by FDA, RedHill has increased the number of subjects to be enrolled from 90 to 120. RedHill believes that the increased number of subjects, as well as other amendments to the study protocol, should improve the study’s statistical powering and reduce the potential impact of non-compliant subjects in meeting the study’s primary endpoint of H. pylori eradication. RedHill is also increasing the total number of clinical sites from 8 to 12 in order to expedite recruitment. In light of the changes to the study protocol, top-line data from the study is currently expected in the first half of 2015.
Following prior discussions with the FDA, RedHill has received authorization from the FDA to pursue a new and significantly broader indication with RHB-105. While current standard treatments for H. pylori are typically indicated to treat patients with active or recent history of ulcers, RedHill's RHB-105 new intended indication will target H. pylori infection as a first line treatment regardless of ulcer status. If approved, RHB-105 may be the first H. pylori eradication therapy to pursue this broader indication, which would significantly expand the potential patient population for the drug.
