Reduction in lesion activity seen as early as 8 weeks

Patients diagnosed with relapsing multiple sclerosis begin to get relief from radiological symptoms as early as the first visit to the clinic after being prescribed ozanimod, researchers suggested at the 2021 virtual meeting of the American Academy of Neurology.

In the post hoc analysis of the RADIANCE study, Patrick Vermersch, MD, PhD, vice-dean of the faculty at the University of Lille, France, reported, “Nominally significant reductions in number of gadolinium enhancement and new and/or enlarging T2 lesions were observed beginning at week 8 for ozanimod 0.92 mg compared with placebo.”

He noted that week eight represented the earliest available magnetic resonance imaging (MRI) timepoint available in the study. Definitive separation from placebo was observed by week 12, he said in his poster presentation.

Statistically, Vermersch noted that the confidence intervals were wide in the placebo group and overlapped with those of ozanimod at all time points in the study, except for the measurements at week 20.

At 24 weeks, researchers reported they could observe no obvious changes in T2 volume or in whole brain atrophy in the overall sample.

The substudy of RADIANCE was undertaken, Vermersch explained, in order to estimate the onset of action of ozanimod. “Knowledge of the onset of action by MRI for disease-modifying therapies in relapsing multiple sclerosis is important for treatment monitoring,” he noted.

To do that, he and colleagues analyzed monthly MRI scans in the 24-week, phase II, randomized, double-blind, placebo-controlled study of ozanimod 0.46 mg/day and 0.92 mg/day in relapsing multiple sclerosis. The study included 248 patients diagnosed with relapsing multiple sclerosis.

In performing the study, the research team acquired MRI scans from patients at baseline, and then at weeks 8, 12, 16, 20, and 24.

“In this post hoc analysis, onset of action was estimated for reduction in number of gadolinium-enhancing lesions—which was the primary outcome,” Vermersch reported. Secondary outcome measures included the number of new/enlarging T2 lesions; T2 lesion volume; the number of new un-enhancing T1 lesions (also referred to as black holes); and whole brain atrophy rate.

The researchers defined “onset of action” as the earliest time point at which a nominally significant difference (P<0.05) in the rate ratio of the least square means and 95% confidence intervals between ozanimod 0.92 mg and placebo occurred and was sustained.

In commenting on the study, Aseff Harel, MD, assistant professor of neurology at Lenox Hill Hospital, Northwell Health, New York City, told BreakingMED, “This study shows that ozanimod is a fast-acting agent, and that on MRI, they were able to see benefits as early as eight weeks after the start of therapy.

“While this is not surprising, it is important to know this from the standpoint of clinical guidance,” Harel said. “It’s important to know when to expect improvement. At eight weeks, there was a minimal improvement that could be observed, but by 12 weeks, the differences were clear cut between ozanimod and placebo treated patients.”

He suggested that this study would be helpful if there were still active lesions on MRI after three months of therapy in some patients to determine whether ozanimod was not working as well as expected. At that point, if there was still activity, then the clinician “might want to try something better with that patient.”

In general, he said, “at the 12-week mark of treatment, we expect to see a substantial effect on brain lesion activity, and that is similar to what we have seen with other drugs used to treat multiple sclerosis.”

Ozanimod 0.92 mg was approved by the FDA in March 2020 for treatment of relapsing forms of multiple sclerosis, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.

The oral medication is dosed once daily. Ozanimod is a sphingosine-1-phosphate receptor modulator. The drug blocks the capacity of lymphocytes to egress from lymph nodes, reducing the number of lymphocytes in peripheral blood. The mechanism by which ozanimod exerts therapeutic effects in multiple sclerosis is unknown but may involve the reduction of lymphocyte migration into the central nervous system. It can be administered without genetic testing.

  1. By eight weeks—or the first time an MRI is performed post-baseline—reduction in brain lesion activity is seen with ozanimod therapy.

  2. This study was presented at a medical meeting, and its findings should be taken with caution until its publication in a peer-reviewed journal.

Edward Susman, Contributing Writer, BreakingMED™

The study was supported by Bristol-Myers Squibb.

Vermersch disclosed relationships with Biogen, Merck, Sanofi, Novartis, Roche, Teva, and Celgene.

Harel disclosed no relationships with industry.

Cat ID: 167

Topic ID: 98,167,728,791,730,131,36,167