New data from the phase 3 DAYBREAK open-label extension trial indicates that ozanimod (Zeposia; BMS) provides sustained reductions in brain volume loss (BVL) over five years in patients with relapsing multiple sclerosis (MS). Brain atrophy, a hallmark of MS, accelerates with disease progression, making these findings clinically significant.
The analysis included 2257 patients with relapsing MS who had previously participated in the phase 3 SUNBEAM and RADIANCE trials. RADIANCE, a 24-month study, and SUNBEAM, a 12-month study, evaluated ozanimod against interferon-beta-1a, leading to ozanimod’s approval in 2019.
ECTRIMS Presentation
At the 40th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), researchers presented data showing that patients receiving continuous ozanimod 0.92 mg maintained stable and low rates of whole brain volume (WBV) loss through month 60 of the open-label extension. The annualized least square mean (LSM) percent change from parent baseline was -0.27 in RADIANCE and -0.35 in SUNBEAM. Patients who continuously received ozanimod had statistically significantly lower LSM percent reductions in WBV compared to those who switched from interferon-beta-1a (nominal P < .05).
Impact on Brain Volume Loss
Led by Jeffrey Cohen, MD, the study highlighted that switching from interferon-beta-1a to ozanimod reduced the rate of WBV loss. The annualized LSM percent changes were -0.48 from RADIANCE baseline to the end of the 24-month double-blind period, and -0.19 from OLE baseline to OLE month 24. A similar trend was observed in patients from SUNBEAM and for annualized LSM percent change in thalamic volume (TV).
Cortical Grey Matter Volume
Patients initially on interferon-beta-1a showed 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. However, this trend reversed 12 months after switching to ozanimod in the OLE, with annualized LSM percent increases relative to OLE baseline of 0.10 in SUNBEAM and 0.20 in RADIANCE. Low annualized LSM percent CGMV loss was observed thereafter.
Ozanimod Mechanism and Prior Findings
Ozanimod, an S1P-modulating therapy, targets S1P1 and S1P5 receptors. The original phase 3 trials demonstrated that ozanimod 0.92 mg/day for up to 24 months significantly reduced clinical relapses and lesion counts on MRI, while also slowing brain volume loss compared to intramuscular interferon-beta-1a. Ozanimod was generally well-tolerated, with fewer treatment-emergent adverse events (TEAEs) leading to discontinuation than interferon-beta-1a.
Long-Term Efficacy
Data presented at the 2024 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum further supported ozanimod’s impact on 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. Additionally, 3- and 6-month confirmed disability progression occurred in 17.2% and 15.2% of patients, respectively. The 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) remained consistent at 60 months.
