Zeposia’s long-term use doesn’t affect heart health, Phase 3 trials show
No major heart rate or echocardiogram changes over year or more of treatment
Long-term use of Zeposia (ozanimod) did not adversely affect the heart of relapsing multiple sclerosis (MS) patients treated for one or two years in Phase 3 clinical trials, with no clinically significant changes in cardiac function reported.
Data on people enrolled in the two studies were retrospectively evaluated, as the therapy can affect heart rate. A similar finding came from an analysis of a Zeposia trial in people with ulcerative colitis, an inflammatory bowel disease.
The study, “Long-Term Cardiac Safety of Ozanimod in a Phase 3 Clinical Program of Ulcerative Colitis and Relapsing Multiple Sclerosis,” was published in the journal Gastroenterology & Hepatology.
Oral Zeposia, an S1P receptor modulator, can slow a person’s heart rate
MS is caused by the immune system mistakenly attacking the myelin sheath, the fatty protective coating around nerve fibers that is essential for efficient nerve cell communication. The resulting inflammation further damages myelin and its producing cells, as well as nerve cells, disrupting neurological signaling and leading to disease symptoms.
Zeposia, approved to treat relapsing forms of MS, is a sphingosine 1-phosphate (S1P) receptor modulator. It works by binding to S1P receptors on inflammatory immune cells and “trapping” them inside lymph nodes — the immune organs where those cells are matured and stored. This prevents inflammatory cells from entering the central nervous system, the brain and spinal cord.
But treatment with S1P modulators can raise cardiovascular issues, including a slow heart rate (bradycardia) and delays in atrioventricular conduction, the passage of blood from the heart’s atria (upper chambers) to the ventricles (lower chambers) before they contract.
Researchers retrospectively evaluated Zeposia’s effects over time on cardiac health in people with relapsing MS enrolled in the Phase 3 SUNBEAM (NCT02294058) and RADIANCE (NCT02047734) clinical trials.
In both studies, patients randomized to oral Zeposia were treated daily at a dose of 0.92 mg (standard) or a lower dose of 0.46 mg. Their cardiac function was monitored by an echocardiogram (ECG) given at an initial screening as a baseline or study start measure, and again 15 days and one year later. An ECG also was given those in RADIANCE trial after two years of treatment.
ECG uses sound waves to create images of the heart and can show blood flow through the heart and its valves.
Continuous one- and two-year treatment with Zeposia was not associated with clinically significant changes in ECG results or heart rate, the study reported.
Among the 882 MS patients evaluated, a treatment-related adverse cardiac event was reported in 30 people (3.4%), including bradycardia in seven patients (0.8%). Two were hospitalized for serious treatment-related heart issues, but their nature was not given.
“The rate of treatment-emergent cardiac AEs [adverse events] was 3.5% in patients with a history of cardiovascular disease vs 3.4% in those without,” the scientists wrote.
The therapy’s cardiac safety was also assessed in people with ulcerative colitis who participated in the Phase 3 True North trial (NCT02435992). Results again showed that the treatment, at a 0.92 mg dose, was not associated with clinically significant changes in ECG results or heart rate.
The mean change in heart rate, observed between baseline and one-year measures, was a reduction of one beat per minute. Treatment-emergent cardiac events also were more common in ulcerative colitis patients with a history of cardiovascular disease than those without it (3.5% vs. 0.6%, respectively).
“In all of the studies, continuous treatment with ozanimod did not lead to clinically significant changes in ECG results or heart rate,” the researchers concluded.
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