Inflammatory Bowel Disease
Inflammatory bowel disease (IBD) is a group of inflammatory and autoimmune conditions that affect the colon and small intestine, typically resulting in severe abdominal pain, weight loss, vomiting and diarrhea. The most common forms of the disease are ulcerative colitis and Crohn’s disease, which are estimated to affect four million people or more in the United States, Europe and Japan.
There are a variety of therapies currently available for patients that suffer from IBD, including agents such as prednisolone, mesalazine, corticosteroids and the more recently developed anti-TNFα therapies. Unfortunately, for many patients these agents are only effective transiently, while in some patients they fail to work at all. Chronic IBD can be a severely debilitating condition, and advanced cases may require surgery to remove the affected region of the bowel and may also require temporary or permanent colostomy or ileostomy. In many cases, surgery does not achieve a permanent cure, and patients suffer a return of the disease.
Working with our collaborators, our research has shown that administration of MultiStem may provide significant benefits in preclinical models of inflammatory-mediated damage to the gastrointestinal (GI) tract. In studies where animals were treated with donor-derived immune cells to induce inflammatory damage in the GI and other organ systems, among animals that were subsequently treated with MultiStem, a significant reduction in inflammatory damage and accelerated healing was observed.
In 2011, we initiated a Phase 2 clinical trial involving administration of MultiStem for the treatment of ulcerative colitis(UC), the most common form of IBD. We and our partner Pfizer selected this as our initial clinical target in the IBD area because the underlying disease tends to be more homogeneous than for Crohn’s disease, and it allows for endoscopic evaluation to determine whether or not the lesions in the colon are healing and the patient is improving.
The Phase 2 study was conducted at clinical centers in the United States and Europe as a randomized, double blind, placebo controlled study that enrolled 108 patients. Eligible patients had moderate-to-severe active UC with a Mayo score of 6 to 12 points and endoscopic score of at least 2 (as measured by modified Baron score) despite prior treatment with corticosteroids, immunosuppressants, or anti-TNF agents. The mean disease duration for patients enrolled in the efficacy stage of the study was 10 years and the other baseline characteristics confirm a patient population with advanced ulcerative colitis. In the study, subjects underwent baseline endoscopic evaluation and then received treatment with either MultiStem or placebo and were then evaluated over several months. After eight weeks, a second endoscopic evaluation was conducted, followed by re-randomization of patients, a second treatment with either MultiStem or placebo, and a subsequent clinical assessment at 16 weeks. Patient follow-up continued for 12 months. Following conclusion of patient enrollment, completion of the final clinical assessment (16 weeks post treatment for the last subject enrolled) and analysis of the initial data, initial results from the study were announced. The results of the trial demonstrated consistent safety, but a single administration of MultiStem was insufficient to achieve a substantial and durable benefit in patients with longstanding chronic and advanced Ulcerative Colitis.
Our partnership with Pfizer concluded in July, 2015.