The approval represents the first and only oral sphingosine 1-phosphate receptor modulator indicated for adults with moderately to severely active ulcerative colitis.
Officials with the FDA have approved ozanimod (Zeposia) as the first and only oral treatment indicated for adults with moderately to severely active ulcerative colitis.
Ozanimod is an oral sphingosine 1-phosphate (S1P) receptor modulator, which could present a new treatment method for ulcerative colitis, according to a press release from Bristol Myers Squibb. The mechanism of action for ozanimod is unknown, although investigators believe that it may work by reducing lymphocyte migration into the intestines. By targeting the S1P receptors on lymphocytes, the drug subsequently reduces the number of lymphocytes in peripheral blood, according to the release.
“Ulcerative colitis can be debilitating and unpredictable for the people living with this chronic inflammatory bowel disease,” said Michael Osso, president and CEO of the Crohn’s and Colitis Foundation, in a press release. “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.”
The approval is based on findings from True North, a pivotal phase 3 trial that evaluated ozanimod as an induction and maintenance therapy in adults with moderately to severely active ulcerative colitis. Trial participants received either ozanimod 0.92 mg or a placebo and received treatment with oral aminosalicylates and/or corticosteroids prior to and during the induction period.
At study entry, the mean age of participants was 42 years, 60% were male, and the mean disease duration was 7 years. A total of 30% of patients had previously failed or were intolerant to tumor necrosis factor (TNF) blockers, 63% of whom received at least 2 biologics, including TNF blockers.
During induction at week 10, the trial met its primary endpoint of clinical remission (18% versus 6%) as well as key secondary endpoints including clinical response (48% versus 26%), endoscopic improvement (27% versus 12%), and endoscopic-histologic mucosal improvement (13% versus 4%).
During maintenance at week 52, the trial also met its primary endpoint of clinical remission (37% versus 19%), as well as the key secondary endpoints of clinical response (60% versus 41%), endoscopic improvement (46% versus 26%), corticosteroid-free clinical remission (32% versus 17%), and endoscopic-histologic mucosal improvement (30% versus 14%). Investigators also noted decreases in rectal bleeding and stool frequency subscores as early as week 2 in patients treated with ozanimod.
“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 Michael Chiorean, MD, AGAF, FASGE, co-director of the IBD Center at the Swedish Medical Center in Seattle, Washington, in the press release. “Zeposia has the potential to be an important new treatment option for adult patients with moderate to severe ulcerative colitis.”
Ozanimod is contraindicated in patients who experienced myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization, or class III/IV heart failure in the past 6 months. It is also contraindicated in patients who have the presence of Mobitz type II second-degree or third-degree atrioventricular block, sick sinus syndrome, or sino-atrial block, unless the patient has a functioning pacemaker.
The drug also has several warnings and precautions, including increased risk of infections, bradyarrhythmia and atrioventricular conduction delays, liver injury, fetal risk, increased blood pressure, respiratory effects, macular edema, and posterior reversible encephalopathy syndrome. The most common adverse reactions in clinical trials included liver test increased, upper respiratory infection, and headache.
“Despite the availability of approved therapies, there is still unmet need and an opportunity to delivery additional treatment options to help patients better manage their disease,” said Adam Lenkowsky, general manager and head of the US Cardiovascular, Immunology, and Oncology division at Bristol Myers Squibb, in the press release. “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.”
US Food and Drug Administration Approves Bristol Myers Squibb’s Zeposia (Ozanimod), an Oral Treatment for Adults with Moderately to Severely Active Ulcerative Colitis [news release]. Bristol Myers Squibb; May 27, 2021. https://news.bms.com/news/details/2021/U.S.-Food-and-Drug-Administration-Approves-Bristol-Myers-Squibbs-Zeposia-ozanimod-an-Oral-Treatment-for-Adults-with-Moderately-to-Severely-Active-Ulcerative-Colitis1/default.aspx. Accessed June 1, 2021.