RedHill Biopharma has received positive feedback from the FDA following a Type C meeting, clearing the pathway for a groundbreaking Phase 2 study of RHB-204 in Crohn's disease patients. The study represents the first clinical trial to specifically target patients infected with Mycobacterium avium subspecies paratuberculosis (MAP), testing the hypothesis that MAP may be a root cause of Crohn's disease.
Novel Approach Targets MAP as Root Cause
The FDA-approved study design allows RedHill to test a fundamentally different approach to Crohn's disease treatment by focusing on MAP-positive patients. This groundbreaking strategy could position RHB-204 as a paradigm-shifting therapy that addresses both the suspected underlying cause of the disease and its symptoms, rather than merely managing inflammation.
A major barrier to previous MAP-targeted therapies has been the difficulty in rapidly and accurately detecting MAP, described as "one of the slowest growing bacteria on the planet." RedHill has addressed this challenge by collaborating with two leading academic centers to provide cutting-edge MAP detection diagnostics, supporting both the study design and potential future commercial application.
Study Design and Endpoints
The Phase 2 study will use mucosal remission as its primary endpoint, which the FDA considers the new gold standard for efficacy evaluation in Crohn's disease. This endpoint will be correlated with MAP status and clinical remission, following FDA guidance. The innovative design incorporating imaging and advanced MAP detection methods to correlate mucosal healing with MAP infection eradication enables a smaller sample size, potentially reducing study costs and accelerating completion timelines.
Strong Clinical Foundation
RHB-204 is a next-generation optimized formulation of RHB-104, which demonstrated compelling efficacy in a randomized, double-blind, placebo-controlled Phase 3 study of 331 patients with active Crohn's disease. The study, published in the peer-reviewed journal Antibiotics, showed RHB-104 plus standard of care to be 64% more effective than standard of care alone, successfully meeting both primary and secondary endpoints.
The Phase 3 data also demonstrated safety and efficacy when used concomitantly with anti-TNFs, immunomodulators, and steroids, suggesting RHB-204 could serve as either a standalone or combination oral therapy. RHB-204 offers enhanced tolerability, safety, and adherence with a 40% reduction in pill burden compared to its predecessor.
Addressing Unmet Medical Need
Current Crohn's disease treatments face significant limitations, with up to 40% of patients failing to respond to anti-TNF treatment and a similar proportion of initial responders losing response over time and experiencing disease flare-ups. Many existing therapies are expensive, require intravenous administration, and carry safety concerns including Black Box Warnings. An effective oral therapy would provide a welcome alternative approach.
According to the Cleveland Clinic, more than 750,000 Americans and approximately 6-8 million people globally have Crohn's disease. The condition causes inflammation of digestive tract tissue leading to abdominal pain, severe diarrhea, fatigue, weight loss, and malnutrition, with no known cure currently available.
Market Opportunity and Regulatory Path
The Crohn's disease market is projected to expand significantly, with sales in the United States, Japan, and five major European markets growing from $13.6 billion in 2024 to $19.1 billion by 2033, representing a compound annual growth rate of 3.87%.
RHB-204 benefits from patent protection through 2041 and is expected to receive transferred pediatric orphan drug designation from RHB-104. The company intends to explore additional regulatory designations including breakthrough therapy designation and fast track status, which could provide additional exclusivity and potential priority review vouchers.
Funding and Development Strategy
RedHill expects funding for this program to be non-dilutive, with the company actively pursuing partnerships and collaborations. An innovation development grant application has been submitted, and discussions are ongoing with external non-dilutive funding sources.
The proprietary RHB-204 formulation contains a fixed-dose combination of clarithromycin, rifabutin, and clofazimine at specific doses designed to safely and effectively treat MAP-positive Crohn's disease. The three antimicrobial agents possess potent intracellular, anti-mycobacterial, and anti-inflammatory properties.
