On February 1, Bristol-Myers Squibb (BMS) announced that the US Food and Drug Administration (FDA) has accepted Zeposia (ozanimod)'s Supplemental New Drug Application (sNDA) for the treatment of moderate to severely active ulcerative colon in adults Inflammation (UC). After submitting the priority review voucher, the US FDA set the target date for the approval of the Prescription Drug User Fee Act (PDUFA) as May 30, 2021.
According to BMS, the sNDA submitted to the US FDA is based on the positive results of the True North study (NCT02435992), which is a pivotal, multi-center, randomized, double-blind, placebo-controlled phase 3 trial that evaluated Zeposia 1 mg against previous Induction and maintenance therapy for adult patients with moderate to severely active UC, and safety.
During the induction period, cohort 1 had a total of 645 patients who were randomly assigned to receive Zeposia (n=429) or placebo (n=216) in a 2:1 ratio, of which 94% and 89% of the patients completed the induction period. At the beginning of the study, the average age of the patients was 42 years, 60% were men, and the average course of the disease was 7 years; the patient characteristics of each treatment group were well balanced. Patients in cohort 1 were treated once a day for 10 weeks. Cohort 2 is an open-label group with 367 patients. The patients received Zeposia treatment once a day for 10 weeks.
In the maintenance phase, patients in cohort 1 or cohort 2 who had a clinical response in the 10th week of the induction period were randomly assigned to the Zeposia group (n=230) or placebo group (n=227) at a ratio of 1:1, and received Treatment up to 52 weeks. Among them, 80% and 54.6% of the patients were treated with Zeposia and placebo, and completed the study. Patients who discontinued treatment due to adverse events caused by treatment included 3 patients who received Zeposia treatment and 6 patients who received placebo treatment; disease recurrence (13.5% in the Zeposia group and 33.9% in the placebo group) was the most discontinued treatment. Common causes. Patients in the placebo group who achieved clinical efficacy at the 10th week of the induction period continued to use the placebo in the blind maintenance period.
In the induction phase cohort 1 and the maintenance phase re-randomized patient group, about 30% of the patients had a history of TNF inhibitor exposure.
All eligible patients have been included in an open-ended extended trial, which is ongoing, to evaluate the long-term efficacy of Zeposia in the treatment of moderate to severe active UC.
The primary endpoint of the study was the proportion of patients in clinical remission based on the comprehensive clinical and endoscopic scores (3-component Mayo score) at the 10th week of the induction period and the 52nd week of the maintenance period. Secondary endpoints included the proportion of patients who achieved clinical efficacy at weeks 10 and 52, the proportion of patients with endoscopic improvement (endoscopy score ≤1) at weeks 10 and 52, and the mucosal membrane at weeks 10 and 52 The proportion of patients who healed, and the proportion of patients who had clinical remission at week 52, week 10. In this study, mucosal healing was defined as an improvement in endoscopic histological remission.
The results showed that True North reached two main clinical endpoints. Compared with placebo, the clinical remission results in the 10th week induction period and the 52nd week maintenance period were highly statistically and clinically significant. At the same time, the overall safety observed in this study is consistent with the known safety of Zeposia in the approved label.
Zeposia is an oral sphingosine 1-phosphate (S1P) receptor modulator that binds to S1P receptors 1 and 5 with high affinity. The drug reduces the ability of lymphocytes to drain from lymph nodes and reduces the number of circulating lymphocytes in the peripheral blood. The mechanism of action of Zeposia in the treatment of UC is unclear, but it may be related to the reduction of lymphocyte migration to the inflamed intestinal mucosa. At present, BMS continues to evaluate the long-term efficacy of Zeposia in the treatment of moderate to severe active UC in an open expansion trial, and evaluates the drug's therapeutic effect on moderate to severely active Crohn's disease in the phase 3 clinical trial project YELLOWSTONE .
Zeposia was approved by the US FDA in March 2020 for the treatment of relapsing multiple sclerosis (RMS) in adults. The European Commission approved Zeposia in May 2020 for the treatment of adult patients with relapsing-remitting multiple sclerosis (RRMS) with active disease with clinical or imaging features. In December 2020, the European Medicines Agency accepted Zeposia's application for marketing authorization for the treatment of moderate to severe adult UC.