IBD is a group of conditions characterized by inflammation in the digestive tract, estimated to affect more than 3.5 million people in the U.S., European Union, and Japan. Two major types of IBD are ulcerative colitis and Crohn’s disease, which usually cause symptoms such as pain, weigh loss, fatigue, and diarrhea.
Treatment for IBD often focuses on reducing inflammation and disease symptoms. Pfizer’s PF-00547659 is a monoclonal antibody that targets the adhesion molecule MAdCAM-1, expressed in the endothelial cells from the gastrointestinal tract, as well the spleen, nasal tissue, bladder, lung, and uterus.
Because MAdCAM-1 binds to proteins expressed on the surface of lymphocytes that cause inflammation, PF-00547659 is able to inhibit the translocation of this lymphocytes from the bloodstream to the intestine.
Pfizer’s PF-00547659 was evaluated in more than 700 patients in Phase 1 and Phase 2 clinical trials. TURANDOT and OPERA are two randomized, multicenter, double-blind, placebo-controlled studies that evaluated the safety and efficacy of PF-00547659 in ulcerative colitis and Crohn’s disease patients, respectively.
Particularly in ulcerative colitis patients who failed to respond at least one previous treatment, PF-00547659 increased the remission rates and mucosal healing at week 12, when compared to patients receiving placebo. In patients with moderate to severe Crohn’s disease, PF-00547659 treatment showed an increased response, although not significant, compared to placebo.
Previous studies had demonstrated that non-selective blockade of the molecule that binds to MAdCAM-1 in lymphocytes led to the appearance of opportunistic infections, such as progressive multifocal leukoencephalopathy (PML), known to attack the central nervous system, possibly due to reduced immune surveillance.
The TOSCA safety study evaluated PF-00547659 in patients with moderate to severe Crohn’s disease with prior treatment with both immunosuppressants (azathioprine, 6-MP or methotrexate) and anti-TNF, to address whether it increased PML susceptibility. The study results demonstrated that the amount of lymphocytes in the cerebrospinal fluid did not change after PF-00547659 treatment, and there was no evidence of PML.
Phase 3 trials are expected to begin after consultation with global health authorities.
“This licensing transaction fits with Shire’s commitment to advancing research and development in select specialty areas, including areas of unmet patient need for gastrointestinal conditions such as IBD,” said Howard Mayer, Shire’s head of Clinical Development in a press release. “We look forward to continuing the development of PF-00547659, a biologic that will benefit from our experience in IBD and across the gastrointestinal space.”