The FDA has approved Bristol Myers Squibb’s Zeposia (ozanimod) 0.92mg for the treatment of adults with moderately to severely active ulcerative colitis (UC). Zeposia (ozanimod) is a sphingosine 1-phosphate (S1P) receptor modulator that binds with high affinity to S1P receptors 1 and 5. Zeposia reduces the capacity of lymphocytes to migrate from lymphoid tissue, reducing the number of circulating lymphocytes in peripheral blood. The mechanism by which Zeposia exerts therapeutic effects in ulcerative colitis is unknown but may involve the reduction of lymphocyte migration into the intestines. Zeposia, an oral medication taken once daily, is the first and only S1P receptor modulator approved for patients with moderately to severely active UC.
“Despite the availability of approved therapies, there is still unmet need and an opportunity to deliver additional treatment options to help patients better manage their disease,” said Adam Lenkowsky, general manager and head, US, Cardiovascular, Immunology and Oncology, Bristol Myers Squibb. “We’re thrilled that our pursuit of transformative science in immunology may benefit patients in their ulcerative colitis treatment by introducing a new option that has a different mechanism of action than available therapies. Zeposia combines disease control through lasting remission and demonstrated safety in a once-daily pill.”
The approval is based on data from True North, a pivotal Phase 3 trial evaluating Zeposia as an induction and maintenance therapy versus placebo in adult patients with moderately to severely active UC. During induction at Week ten (Zeposia n=429 versus placebo n=216) the trial met its primary endpoint of clinical remission (18% versus 6%, p<0.0001) as well as key secondary endpoints, including clinical response (48% versus 26%, p<0.0001), endoscopic improvement (27% versus 12%, p<0.0001) and endoscopic-histologic mucosal improvement (13% versus 4%, p<0.001) for Zeposia versus placebo, respectively.
During maintenance at Week 52 (Zeposia n=230 versus placebo n=227) the trial met its primary endpoint of clinical remission (37% versus 19%, p<0.0001) as well as key secondary endpoints, including clinical response (60% versus 41%, p<0.0001), endoscopic improvement (46% versus 26%, p<0.001), corticosteroid-free clinical remission (32% versus 17%, p<0.001) and endoscopic-histologic mucosal improvement (30% versus 14%, p<0.001) for Zeposia versus placebo, respectively. Decreases in rectal bleeding and stool frequency subscores were observed as early as Week two (i.e., one week after completing the required seven-day dosage titration) in patients treated with Zeposia.
“In True North, Zeposia demonstrated efficacy for endpoints such as clinical remission, endoscopic and histological mucosal improvement and safety. All are very relevant considerations for patients with ulcerative colitis,” said Dr Michael Chiorean, co-director of IBD Center, Swedish Medical Center, Seattle, Washington. “Zeposia has the potential to be an important new treatment option for adult patients with moderate to severe ulcerative colitis.”
“Ulcerative colitis can be debilitating and unpredictable for the people living with this chronic inflammatory bowel disease,” said Michael Osso, President & CEO of the Crohn’s & Colitis Foundation. “The approval of this new oral treatment is welcome news for our community and provides hope to many patients who are looking for new options to achieve symptom relief and remission.”
Bristol Myers Squibb is continuing to evaluate Zeposia in an open-label extension trial, which is ongoing and designed to assess the longer-term profile of Zeposia for the treatment of moderately to severely active ulcerative colitis. The company is also investigating Zeposia for the treatment of moderately to severely active Crohn’s disease in the ongoing Phase 3 YELLOWSTONE clinical trial program.
The European Medicines Agency (EMA) validated Bristol Myers Squibb’s Marketing Authorization Application for Zeposia for the treatment of adults with moderately to severely active ulcerative colitis in December 2020. A regulatory decision from the EMA is expected in the second half of 2021.