Ozanimod Treatment Results in Higher Rates of No Evidence of Disease Activity vs Interferon ß-1a

Ludwig Kappos, MD

In a post hoc analysis of the phase 3 RADIANCE trial (NCT02047734) and its open-label extension DAYBREAK (NCT02576717), a higher proportion of patients with relapsing multiple sclerosis (MS) achieved no evidence of disease activity status 3 or 4 (NEDA-3 and NEDA-4) following treatment with oral ozanimod (Zeposia; Bristol Myers Squibb) vs intramuscular interferon ß-1a (IFN).¹

At months 12 and 24 of RADIANCE, investigators observed NEDA-3 rates of 31.2% and 24.6% (P <.05) for ozanimod-treated patients vs 26.9% and 17.0% for those on IFN, respectively. In DAYBREAK, rates were 16.2% (P <.05), 13.4% (P <.05), and 10.7% with continuous ozanimod at months 12, 24, and 36, respectively, compared with rates of 9.8%, 8.6%, and 7.4% for those on/transitioned from IFN.

These findings were presented at the 2022 American Academy of Neurology (AAN) Annual Meeting, April 2-7, in Seattle, Washington, by lead investigator Ludwig Kappos, MD, professor of neurology, University Hospital Basel, Switzerland. “We see the effects in the first year were repeated over time, and that a significant number of patients remained disease activity free under these quite strict criteria,” he told NeurologyLive^®. "Those who had evidence of disease activity mainly had this through MRIs, so through lesions that occurred in their regularly repeated and standardized assessments."

Ozanimod, a sphingosine-1 phosphate (S1P) receptor, has been FDA-approved to treat relapsing forms of MS since March 2020. In this analysis, NEDA-3 was defined as no new gadolinium-enhancing lesions, no new/enlarging T2 lesions, no relapses, and no progression on Expanded Disability Status Scale (EDSS) scores from baseline. Achieving NEDA-4 required NEDA-3 status plus annualized whole brain volume loss of less than 0.4%.

For those on continuous ozanimod, 21.5% and 14.0% (P <.05) of patients achieved NEDA-4 in RADIANCE at months 12 and 24, respectively, compared with rates of 16.3% and 7.8% for those on IFN. The therapeutic effect continued to show greater results than IFN in DAYBREAK, with NEDA-4 rates of 10.0%, 10.4%, and 10.3% in months 12, 24, and 36 vs rates of 5.9%, 6.2%, and 6.3% for those on/transitioned from IFN, respectively.

Rebaselining to month 12 resulted in greater rates of achieving NEDA-3 and NEDA-4 for patients on continuous ozanimod vs those who transitioned from IFN. After rebaselining, NEDA-3 rate at RADIANCE month 24 was 52.6% (P <.05), and DAYBREAK months 12, 24, and 36, rates were 33.1% (P <.05), 26.3% (P <.05), and 21.3% in ozanimod-treated patients, respectively. In those same trials, those NEDA-3 rates were 33.4%, 20.5%, 17.4%, and 14.8% for those on/transitioned from IFN. Rebaselined rates of NEDA-4 were 33.5% (P <.05), 20.0% (P <.05), 16.7%, and 14.1% for continuous ozanimod and 19.7%, 11.7%, 11.2%, and 11.0% for those on/transitioned from IFN, respectively.

RADIANCE was a multicenter, double-blind, double-dummy study that randomized patients with MS in a 1:1:1 fashion to either daily ozanimod 1.0 mg or 0.5 mg or weekly intramuscular IFN 30 μg, with annualized relapse rate (ARR) as the primary end point. After 24-months of treatment, adjusted ARRs were 0.17 (95% CI, 0.14-0.21) for ozanimod 1.0 mg, 0.22 (95% CI, 0.18-0.26) with ozanimod 0.5 mg, and 0.28 (95% CI, 0.23-0.32) for IFN, with rate ratios vs IFN of 0.62 (95% CI, 0.51-0.77; P <.0001) and 0.79 (95% CI, 0.65-0.96; P = .0167) for the ozanimod 1.0 mg and 0.5 mg groups, respectively.²

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REFERENCES
1. Kappos L, Comi G, Selmaj K, et al. Evaluating no evidence of disease activity in patients with relapsing multiple sclerosis: post hoc analysis of the phase 3 RADIANCE and open-label extension studies of ozanimod. Presented at: 2022 AAN Annual Meeting; April 2-7; Seattle, Washington. Abstract 0839

2. Cohen JA, Comi G, Selmaj K, et al. Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (RADIANCE): a multicenter, randomized, 24-month, phase 3 trial. Lancet Neuro. 2019;18(11):1021-1033.