Crohn's disease

RHB-104 is a potentially groundbreaking, proprietary investigational drug in oral capsule formulation, with potent intracellular, antimycobacterial and anti-inflammatory properties.

Crohn’s disease is an inflammatory disease of the gastrointestinal system with significant unmet needs. The inflammation caused by Crohn's disease can lead to abdominal pain, severe diarrhea, rectal bleeding, weight loss, malnutrition, fever and other symptoms, the range and severity of which vary. Current therapies target symptomatic relief, are widely considered to be of limited efficacy in the long term, and are associated with numerous side effects.

The development of RHB-104 is based on increasing evidence supporting the hypothesis that Crohn’s disease is caused by the Mycobacterium avium subspecies paratuberculosis (MAP) infection in susceptible patients rather than being an autoimmune disease.

RedHill announced in July 2018 positive top-line results from its global first Phase 3 clinical study of RHB-104 in Crohn’s disease (MAP US). The study was designed to evaluate the safety and efficacy of fixed-dose RHB-104 in patients with moderately to severely active Crohn's disease.

Top-line results demonstrated superiority of RHB-104 over placebo in achieving remission at week 26, defined as Crohn’s Disease Active Index (CDAI) value of less than 150, the primary endpoint of the study. The proportion of patients meeting the primary endpoint was significantly greater in the RHB-104 group compared to placebo (36.7% vs. 22.4%, p= 0.0048).

The study also successfully met key secondary endpoints, demonstrating consistent benefit to Crohn’s disease patients treated with RHB-104.

The MAP US study is registered on, a web-based service by the U.S. National Institute of Health which provides public access to information on publicly and privately supported clinical studies.

Additional clinical studies are most likely to be required to support a U.S. New Drug Application (NDA) for RHB-104, if filed. 

Several clinical trials were conducted with earlier formulations of RHB-104, including an Australian Phase 3 study conducted by 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 3 MAP US study. The formulation of RHB-104 is covered by several issued and pending patents.

As part of its development efforts for RHB-104, RedHill is developing a diagnostic test to aid in detecting the presence of MAP in Crohn's disease patients. 

*Selected publications:

  1. R.J. Is Crohn’s disease caused by a mycobacterium? Comparisons with leprosy, tuberculosis, and Johne’s disease. THE LANCET Infectious Diseases 2003, Vol 3, PP 507-514.
  2. A. M.; Kapur. V. The evidence for Mycobacterium paratuberculosis in Crohn’s disease. Current Opinion in Gastroenterology. 2008, Vol 24, PP 17–21.
  3. Borody T.J.; Leis. S.; Warren. E.F.; Surace. R. Treatment of severe Crohn’s disease using antimycobacterial triple therapy–approaching a cure? Digestive and Liver Disease 2002, Vol 34, 1, PP 29-38.
  4. Taylor, J. H. Treatment with drugs active against Mycobacterium avium subspecies paratuberculosis can heal Crohn’s disease: more evidence for a neglected Public Health tragedy. Digestive and Liver Disease. 2002, Vol 34, PP 9-12.
  5. T.J.; Bilkey. S.; Wettstein. A. R.; Leis. S.; Pang. G.; Tye. S.; Anti-mycobacterial therapy in Crohn’s disease heals mucosa with longitudinal scars Digestive and Liver Disease. 2007, Vol 39, 5, PP 438-44.
  6. W.; Ghobrial. G.; Chehtane. M.; Naser. S. A. Successful Treatment of a Crohn’s Disease Patient Infected with Bacteremic Mycobacterium Paratuberculosis. American Journal of Gastroenterol. 2007, Vol 102, PP 689-691.
  7. C.D.; Wagner. J.; Boniface. K.; Vaughan. J.; Michalski. W. P.; Catto-Smith. A. J.; Cameron. Don .J.S.; Bishop. R. F.Mycobacterium aviumsubspecies paratuberculosis in children with early-onset Crohn’s disease. Inflammatory Bowel Diseases. 2009, Vol 15, 11, PP 1643-1655.
  8. K.; Kaevska. M. Mycobacteria in water, soil, plants and air: a review. Veterinarni Medicina. 2012, Vol 57, 12, PP 623-679
  9. Agrawal G, Borody TJ & Chamberlin W. ’Global warming’ to Mycobacterium avium subspecies paratuberculosis. Future Microbiol. (2014) 9(7), 829–832.
  10. Naser SA et al. Mycobacterium avium subspecies paratuberculosis causes Crohn's disease in some inflammatory bowel disease patients. World J Gastroenterol 2014 June 21; 20(23): 7403-7415.
  11. Mendoza JL et al. High prevalence of viable Mycobacterium avium subspecies paratuberculosis in Crohn’s disease. World J Gastroenterol 2010 September 28; 16(36): 4558-4563.
  12. Chiodini RJ et al. Crohn’s disease and the mycobacterioses: A quarter century later. Causation or simple association? Critical Reviews in Microbiology, 2012; 38(1): 52–93.
  13. McNees AL et al. Mycobacterium paratuberculosis as a cause of Crohn’s disease Expert Rev. Gastroenterol. Hepatol. 9(12), (2015).
  14. Alcedo KP, Thanigachalam S, Naser SA. RHB-104 triple antibiotics combination in culture is bactericidal and should be effective for treatment of Crohn’s disease associated with Mycobacterium paratuberculosis, Gut Pathogens, 2016, 8:32.
  15. Qasem A, Naser AE, Naser SA. The alternate effects of anti-TNFα therapeutics and their role in mycobacterial granulomatous infection in Crohn’s disease, EXPERT REVIEW OF ANTI-INFECTIVE THERAPY, 2017
  16. Naser SA, Ghobrial G, Romero C, Valentine JF. Culture of Mycobacterium avium subspecies paratuberculosis from the blood of patients with Crohn’s disease. The Lancet Vol 364 September 18, 2004.
  17. Lee A, Griffiths TA, Parab RS, King RK, Dubinsky MC, Urbanski SJ, Wrobel I, Rioux KP. Association of Mycobacterium avium subspecies paratuberculosis With Crohn Disease in Pediatric Patients, JPGN _ Volume 52, Number 2, February 2011