Ozanimod produces favorable long-term cardiac safety profile in UC, MS
SAN DIEGO — Minimal long-term cardiac safety findings were reported with ozanimod treatment in patients with ulcerative colitis and relapsing multiple sclerosis, according to research presented at Digestive Disease Week 2022.
“Ozanimod is a newly approved, oral sphingosine-1-phosphate (S1P) receptor modulator that specifically targets S1P1 and S1P5 and prevents lymphocyte migration to the intestines. It's approved in the U.S. and in Europe for the treatment of moderately to severely active UC as well as relapsing multiple sclerosis,” Millie Dascomb Long, MD, MPH, of the University of North Carolina at Chapel Hill, said. “S1P1 receptors play an important role in regulating cardiac function. ... A previous analysis demonstrated that the first dose administration in ozanimod had minimal effect on cardiac function.”
Seeking to evaluate the long-term cardiac safety profile of continuous ozanimod 0.92 mg treatment, Long and colleagues analyzed patients from the phase 3 UC True North trial as well as pooled results from the multiple sclerosis (MS) SUNBEAM and RADIANCE trials.
In the True North trial, patients in the first cohort received either double-blind ozanimod or placebo and patients in the second cohort received open-label ozanimod during induction; patients who had a clinical response at 10 weeks continued to the maintenance period. Researchers performed ECGs at screening, day 1, week 10 and week 52, and they monitored heart rate at every visit.
In the MS trials, researchers monitored ECGs at screening, baseline, day 15 and study conclusion and heart rate every 3 months until the end of the study period.
According to study results, continuous ozanimod use did not correlate with any clinically significant changes in heart rate or ECG among patients enrolled in the UC trial. Although incidence of cardiac-related treatment-emergent adverse events remained low during induction, 1.3% of patients (3/230 patients) experienced adverse events during the maintenance period. Further, researchers observed higher incidence among patients with a prior history of cardiovascular disease (3.5%) vs. those without (0.6%).
In the MS studies, Long and colleagues observed no clinically significant change in heart rate or ECGs associated with long-term ozanimod use. In addition, incidence of cardiac-related adverse events was similarly low among patients with (3.5%) vs. without (3.4%) a prior history of CVD.
“In both of these trials, both UC and MS, clinically significant changes in heart rate were infrequent and manageable, and slight increases in blood pressure were observed. The symptoms tended to stabilize over time and the occurrences of hypertension were infrequent and manageable,” Long concluded. “Ozanimod does not increase the risk for thromboembolic events, cardiovascular death, myocardial infarction or stroke.”
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Long MD, et al. Abstract 15. Presented at: Digestive Disease Week; May 21-24, 2022; San Diego (hybrid meeting).
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