RedHill Biopharma Ltd., a specialty biopharmaceutical company, announced that the last patient has been enrolled in the phase III study with RHB-104 for Crohn’s disease (MAP US study). Top-line results are expected to be announced in mid-2018.

The MAP US study is a randomized, double-blind, placebo-controlled first phase III study evaluating the safety and efficacy of RHB-104 in subjects with moderately to severely active Crohn’s disease (defined as Crohn’s Disease Active Index (CDAI) between 220 and 450). The primary endpoint of the MAP US study is disease remission, defined as a reduction in CDAI to less than 150 at week 26. The study enrolled 331 patients across approximately 150 clinical sites in the US, Canada, Europe, Israel, Australia and New Zealand.

Two pre-planned independent Data and Safety Monitoring Board (DSMB) meetings have been held to review data from the MAP US study, in which unanimous recommendations were given to continue the study without any changes to the protocol, investigator’s brochure, study conduct or informed consent form. At the first DSMB meeting, held in December 2016, safety data from the study was reviewed. At the second DSMB meeting, held in July 2017, safety and efficacy data from the first 222 subjects who had completed week 26 assessments of the study was reviewed.

In addition, an open-label extension Phase III study (the MAP US2 study) continues to evaluate the safety and efficacy of RHB-104 in subjects who remain with active Crohn’s disease (CDAI = 150) after 26 weeks of blinded study therapy in the ongoing phase III MAP US study. These subjects have the opportunity to receive treatment with RHB-104 for a 52-week period in the open-label MAP US2 extension study. The data collected in the MAP US2 study will be supplemental to the MAP US study data. The MAP US2 study’s primary endpoint is disease remission at week 16, defined as CDAI of less than 150. The MAP US2 study is planned to enroll approximately 50-70 subjects in the US, Canada, Europe, Israel and New Zealand. Additional open-label studies with RHB-104 for Crohn’s disease are being planned to generate further supportive clinical data for potential future marketing applications.

Additional clinical studies are likely to be required to support a US New Drug Application (NDA) for RHB-104. If the MAP US study results are positive, RedHill will meet with the US Food and Drug Administration (FDA) and key opinion leaders to present the data package and discuss the preferred development path.

The worldwide sales of Crohn’s disease therapies exceeded $7.6 billion in 2016(1).

In addition to the ongoing phase III studies with RHB-104 for Crohn’s disease, RedHill plans, subject to regulatory approvals, to initiate a pivotal Phase III study with RHB-104 for the treatment of nontuberculous mycobacteria (NTM) infections in the US. in the first half of 2018. RHB-104 was granted Qualified Infectious Disease Product (QIDP) status by the FDA for the treatment of NTM infections. QIDP designation allows for Fast-Track development status, Priority Review of an NDA, if filed, and an additional five years of US market exclusivity on top of the standard exclusivity period or Orphan Designation exclusivity period, as applicable, for a total US market exclusivity of 8-12 years.

Currently in a first phase III study for the treatment of Crohn’s disease (the MAP US study), with top-line results expected in mid-2018, RHB-104 is a proprietary, orally-administered, potentially ground-breaking oral antibiotic combination therapy, with potent intracellular, antimycobacterial and anti-inflammatory properties. RHB-104 is based on increasing evidence supporting the hypothesis that Crohn’s disease is related to 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. Clinical trials conducted with earlier formulations of RHB-104 include an Australian Phase III study conducted by Pharmacia/Pfizer. RedHill has conducted several supportive studies with the current formulation of RHB-104 and a long-term population pharmacokinetic (pop-PK) study is ongoing as part of the phase III MAP US study. Additionally, an open-label extension Phase III study (the MAP US2 study) is ongoing to assess the safety and efficacy of RHB-104 in subjects who have completed week 26 assessments in the ongoing Phase III MAP US study and remain with active Crohn’s disease (CDAI = 150) at week 26. RHB-104 is covered by several issued and pending patents. RHB-104 was granted Qualified Infectious Disease Product (QIDP) designation by the US FDA for the treatment of nontuberculous mycobacteria (NTM) infections, providing a Fast-Track development pathway, as well as NDA Priority Review and an additional five years of U.S. market exclusivity, if approved. A pivotal Phase III study with RHB-104 for NTM infections is planned to be initiated. RedHill also completed a Phase IIa, proof-of-concept clinical study, evaluating RHB-104 as an add-on therapy to interferon beta-1a in subjects treated for relapsing-remitting multiple sclerosis (the CEASE MS study), supporting additional studies.