Treatment with SHP647 (also known as PF-00547659) significantly decreased remission rates in a Phase 2 clinical trial of patients with ulcerative colitis, a type of inflammatory bowel disease (IBD). The drug is licensed by Shire and was originally designed by Pfizer.
Results of this trial were published in The Lancet with the title, “Anti-MAdCAM antibody (PF-00547659) for ulcerative colitis (TURANDOT): a phase 2, randomised, double-blind, placebo-controlled trial.”
The two major types of IBD are ulcerative colitis and Crohn’s disease, which usually cause symptoms such as pain, weight loss, fatigue, and diarrhea.
SHP647 is a monoclonal antibody that inhibits a molecule called MAdCAM-1, which is expressed in surface cells from the gastrointestinal tract. This binding blocks the translocation of lymphocytes (the immune system’s cells participate in inflammation) from the bloodstream to the intestine, thereby preventing inflammation.
The Phase 2 TURANDOT study (NCT01620255) was a randomized, multicenter, double-blind, placebo-controlled study investigating the safety and efficacy of SHP647 in ulcerative colitis patients. The trial enrolled 357 patients who were assigned to either receive SHP647 in four different doses – 7.5 mg, 22.5 mg, 75 mg, and 225 mg – or a placebo.
The study’s primary endpoint was the number of patients achieving disease remission at week 12. Results showed that remission rates at week 12 were higher in patients treated with 22.5 mg (12 of 72 patients, or 16.7%), followed by those treated with 75 mg (11 of 71 patients, or 15.5%). Remission rates were significantly greater than the placebo group in three of the four SHP647 treatment groups.
The treatment was well-tolerated, with less than 5% of patients discontinuing it due to adverse effects. More studies with larger treated patient populations during a longer period are needed, however, to fully investigate SHP647’s safety, study authors said.
“The TURANDOT trial is the first study to investigate a new biologic, an anti-MAdCAM antibody, as a potential treatment for ulcerative colitis, a chronic intestinal disease with high unmet need,” Séverine Vermeire, MD, the trial’s lead investigator, said in a news release. “These statistically significant results demonstrate the role that cell adhesion plays in ulcerative colitis and suggest that inhibition of cell adhesion mediated by MAdCAM may result in a potential treatment for patients suffering with this disease.”
“For patients with ulcerative colitis, there is a critical need for new treatment options,” Philip Vickers, PhD, Shire’s global head of research and development, said. “In line with Shire’s commitment to researching and developing therapeutic advances for patients with GI conditions, we are encouraged by the statistically significant results of the TURANDOT trial and the potential for our anti-MAdCAM antibody to become an important therapeutic option for patients with ulcerative colitis.”
Shire plans to begin a pivotal Phase 3 trial for SHP647 in the second half of 2017.