Promising phase II results for ozanimod in MS

By Eleanor McDermid

The selective sphingosine 1-phosphate receptor (S1PR) inhibitor ozanimod significantly reduces lesion activity in patients with relapsing-remitting multiple sclerosis (MS), shows a phase II study published in The Lancet Neurology.

Ozanimod inhibits only S1PR1 and S1PR5, in contrast with the nonselective fingolimod, which modulates S1PR1, S1PR3, S1PR4 and S1PR5. This should, in theory, reduce unwanted off-target effects caused by interactions with, in particular, S1PR3, say Jeffrey Cohen (Cleveland Clinic, Ohio, USA) and RADIANCE study co-authors.

They add that the low peak plasma dose of ozanimod also reduces the risk of cardiac effects on first administration, in addition to which the team introduced the drug slowly, beginning at 0.25 mg/day and titrating up to the full dose of 0.5 or 1.0 mg/day on day 8.

At the time of first administration, the team noted a "mild blunting of the normal circadian increase in heart rate". The most notable cardiac side effect was orthostatic hypotension, which occurred in 4-5% of ozanimod-treated patients, but also in 2% of the placebo group - mostly during the first day when orthostatic blood pressure was monitored hourly.

Other adverse effects were mostly mild or moderate, and none of the four serious events were thought to be related to treatment. Events thought at least possibly related to treatment occurred in 13% of the placebo group, and 22% and 18% of the 0.5 and 1.0 mg ozanimod groups, respectively.

Patients using other S1PR inhibitors were excluded from the study, and washout periods were required for those using drugs other than interferon beta or glatiramer acetate.

Treatment continued for 24 weeks, and the 88 patients taking placebo had a cumulative average of 11.1 gadolinium-enhancing lesions on four magnetic resonance imaging scans during the last 12 weeks of treatment. By contrast, the 87 and 83 patients taking, respectively, 0.5 and 1.0 mg ozanimod had an average of just 1.5 active lesions.

Likewise, ozanimod treatment reduced the cumulative number of new and enlarging T2 lesions, from 9.0 with placebo to an average of 1.4 with the 0.5 mg dose and 0.8 with the 1.0 mg dose.

In a linked commentary, Per Soelberg Sørensen (Copenhagen University Hospital Rigshospitalet, Denmark) describes the findings as "promising" but cautions that the study is "rather small".

"Only efficacy and safety results of phase 3 trials will determine whether ozanimod has a more favourable risk-benefit profile than fingolimod and could be classified as a first-line drug by [the European Medicines Agency]."

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