Allergan has initiated two global clinical research programs for brazikumab, an investigational drug being studied for inflammatory bowel disease (IBD). Intrepid (Crohn’s disease) and Expedition (ulcerative colitis), will evaluate the safety and efficacy of brazikumab and will investigate the role of biomarkers in determining a predictive response of brazikumab in patients with IBD. They are the first active comparator studies of an IL-23 inhibitor therapy in IBD to evaluate biomarkers as potential predictors of treatment response and the first randomized comparison of an IL-23 inhibitor versus Humira (adalimumab) in Crohn’s disease and Entyvio (vedolizumab) in ulcerative colitis.
Despite advancements in IBD treatments, up to 80 percent of patients will never achieve full disease remission.i In fact, many patients face rapid disease progression early in their treatment course due to ineffective or delayed therapies,iiwhich can result in irreversible gastrointestinal (GI) damage and potential surgery.iii
“Due to the complex nature and multifactorial causes of IBD, it can be challenging to predict which patients need and will respond to early advanced treatments,” said Bruce E. Sands, MD, MS, Dr. Burrill B. Crohn Professor of Medicine at Mount Sinai Hospital in New York. “If we are able to identify whether certain biomarkers can predict a response to treatment, we may be able to select the most appropriate therapy for patients earlier.”
Allergan is initiating the Intrepid and Expedition programs following a Phase 2 clinical trial that showed higher anti-inflammatory response and remission rates with brazikumab in patients with Crohn’s disease who had higher levels of a key IBD biomarker compared to those who had lower levels.iv
“The personalized study design of the Intrepid and Expedition research programs reflect Allergan’s commitment to finding new approaches in how we address the needs of patients with our medicines,” said David Nicholson, chief R&D officer, Allergan. “These programs are part of our growing focus in gastroenterology, which will become even more significant for Allergan in the coming years.”
More about Intrepid and Expedition
Intrepid is a patient-centric Phase 2b/3, multicenter, randomized, double-blind, double-dummy, placebo- and active-controlled, parallel-group, Crohn’s disease program. In Stage 1 (Phase 2b), brazikumab will be compared to placebo and Humira (adalimumab) and in Stage 2 (Phase 3) brazikumab will be compared to Humira only. Approximately 450 patients will be enrolled in Stage 1 and 690 patients in Stage 2. To the benefit of study participants, all will have post-trial access to study treatments.
Expedition is starting with a Phase 2, multicenter, randomized, double-blind, double-dummy, placebo- and active-controlled, parallel-group, study of patients with ulcerative colitis. The safety and efficacy of brazikumab will be compared to placebo or Entyvio (vedolizumab). Approximately 375 patients will be enrolled. Biomarker learnings from this study will be applied to the planned Phase 3 part of the program.
The primary endpoints of Intrepid include evaluations of endoscopic response and clinical remission based on loose stool frequency and abdominal pain scores.The primary endpoints of Expedition include evaluations of endoscopic response and clinical remission based on loose stool frequency and rectal bleeding. In both programs, patients who previously received standard biologic therapy (biologic-intolerant or -refractory) and those who were never treated with biologic therapy (biologic-naïve) will be enrolled. Patients who received conventional therapies, such as corticosteroids or immunomodulators, will also be included.
i Feldman, P. A., Wolfson, D., & Barkin, J. S. (2007). Medical Management of Crohn’s Disease. Clinics in Colon and Rectal Surgery, 20(4), 269–281. https://doi.org/10.1055/s-2007-991026
ii Facts about Inflammatory Bowel Diseases. (2011, May 1) CCFA. https://www.crohnscolitisfoundation.org/resources/facts-about-inflammatory.html. Retrieved on Sept. 18, 2018.
iii Lichtenstein, Gary R. et al. (2018). “ACG Clinical Guideline: Management of Chron’s Disease in Adults.” The American Journal of Gastroenterology, 113, 481–517
iv Sands, Bruce E. et al. (2017). Efficacy and Safety of MEDI2070, an Antibody Against Interleukin 23, in Patients with Moderate to Severe Crohn’s Disease: A Phase 2a Study. Gastroenterology, Volume 153, Issue 1, 77 – 86.e6
(Source: Allergan plc)
Filed Under: Drug Discovery