Sustained Reductions of Brain Atrophy Observed With S1P Modulator Ozanimod

New long-term data from the phase 3 open-label DAYBREAK trial (NCT02576717), an extension study, showed that treatment with ozanimod (Zeposia; BMS) resulted in reductions in brain volume loss (BVL) that were sustained for up to 5 years in patients with relapsing multiple sclerosis (MS). Brain atrophy, the gradual loss of brain volume, is a common and progressive feature of MS that accelerates with disease progression.¹

The analysis included 2257 patients with relapsing MS who previously completed either of the phase 3 SUNBEAM (NCT02294058) or RADIANCE (NCT2047734) trials. RADIANCE, the first of the 2 studies, was a 24-month, double-blind, double-dummy study that assessed the safety and efficacy of ozanimod, a sphingosine 1-receptor modulator (S1P), versus interferon-beta-1a. SUNBEAM was similar in design; however, it lasted only 12 months instead. Both trials were used as supportive data for ozanimod’s approval in 2019.

Presented at the 40th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held September 18-20 in Copenhagen, Denmark, patients who received continuous ozanimod 0.92 mg demonstrated stable and low rates of whole brain volume (WBV) through month 60 of the open-label extension (OLE; annualized least square mean [LSM] percent change from parent baseline: RADIANCE, –0.27; SUNBEAM: –0.35). Compared with those who switched from interferon-beta-1a, patients who received continuous ozanimod had statistically significantly (nominal P <.05) lower LSM percent reductions in WBV through OLE month 48 in RADIANCE and OLE month 60 in SUNBEAM.

Led by Jeffrey Cohen, MD, director of the clinical neuroimmunology fellowship at Cleveland Clinic, the study showed that switching from interferon-beta-1a to ozanimod reduced rates of WBV loss. Overall, investigators reported annualized LSM percent changes of –0.48 from RADIANCE baseline to the end of the 24-month double-blind period, and changes of –0.19 from OLE baseline to OLE month 24. Notably, a similar pattern was observed in patients from SUNBEAM and for annualized LSM percent change in thalamic volume (TV).

READ MORE: Remyelinating Effects Seen With Cladribine in Relapsing Multiple Sclerosis

In the analysis, those originally assigned to interferon-beta-1a demonstrated high annualized LSM percent reductions in cortical grey matter volume (CGMV), with changes of –1.02 at month 12 in SUNBEAM and –0.59 in RADIANCE. Despite these data, results showed that this trend reversed 12 months after switching to ozanimod in the OLE (annualized LSM percent increase relative to OLE baseline: SUNBEAM, 0.10; RADIANCE, 0.20), with low annualized LSM percent CGMV loss observed thereafter.

Ozanimod is an S1P-modulating therapy that specifically targets S1P1 and S1P5 receptors. In the original phase 3 studies, treatment with ozanimod 0.92 mg/day for up to 24 months resulted in significant reductions in clinical relapses and lesions counts on MRI and slowed brain volume loss relative to intramuscular interferon-beta-1a. Overall, ozanimod was considered well tolerated, with fewer treatment-emergent adverse events (TEAEs) leading to discontinuation than interferon-beta-1a.

Earlier this year, at the 2024 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, February 29 to March 2, in West Palm Beach, Florida, data from DAYBREAK continued to highlight ozanimod’s impact on measures of disease activity and progression. After 72 months of treatment, the adjusted annualized relapse rate (ARR) was 0.098 (95% CI, 0.082‒0.117) and 67% of patients were relapse-free. In addition, investigators observed that 3- and 6-month confirmed disability progression occurred in 17.2% and 15.2% of patients, respectively. Notably, adjusted mean number of new/enlarging T2 lesions per scan (range, 0.789-0.932) and adjusted mean number of gadolinium-enhancing (GdE) lesions (0.062-0.077) were similar at 60 months.²

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REFERENCES
1. Cohen J, Arnold D, DeLuca J, et al. Whole Brain, Cortical Grey Matter, and Thalamic Volume Changes During 5–7 Years of Ozanimod in Relapsing MS: Final Results From the DAYBREAK Open-Label Extension Study. Presented at ECTRIMS Congress; September 18-20, 2024; Copenhagen, Denmark. ABSTRACT 1623/141
2. Selmaj KW, Steinman L, Comi G, et al. Long-term Safety and Efficacy of Ozanimod in Relapsing Multiple Sclerosis: Final Analysis of the DAYBREAK Open-label Extension Study. Presented at ACTRIMS Forum 2024; February 29 to March 2; West Palm Beach, Florida. P090.