Relapsing multiple sclerosis (RMS) is the most common phenotype of multiple sclerosis (MS) characterized by episodes of transient exacerbations of neurological disability.¹ Ozanimod is a sphingosine 1-phosphate (S1P) receptor 1 and 5 modulator.² Its effect on RMS have been studied in multiple clinical trials, and it has been approved for the treatment of adults with RMS in many countries.² At the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2024, results from DAYBREAK, the long-term extension study of the safety and efficacy of ozanimod was reported.² Ozanimod was found to be well-tolerated and demonstrated sustained efficacy.²

MS is a chronic autoimmune disease that affects the central nervous system (CNS).³ It is characterized by inflammation, demyelination and axonal loss.³ It is the most frequent cause of neurological disability in young people, affecting around 2.8 million people worldwide, resulting in high consumption of healthcare resources and incur significant costs.^1,3,4 The most common phenotype of MS is RMS.¹ Patients with RMS experience transient episodes of exacerbations of neurological disability.¹ Immunomodulatory therapies and corticosteroids are the most common prevention and management strategies.¹ However, the effects of current treatments are limited and there is a continuous search for more efficient therapies.¹

S1P is a phospholipid involved in the migration of lymphocytes and other physiological processes.⁵ There are 5 types of S1P receptors, and it was found that the antagonism of S1P₁ prevents the release of immune cells from lymph nodes, while modulation of S1P₅ may be neuroprotective.⁵ Ozanimod is an immunomodulator that selectively targets the S1P₁ and S1P₅ receptors.² Previously, in RADIANCE, a phase 3 study conducted over a period of 2 years, ozanimod was found to be an effective therapy for RMS.⁶ However, longer-term effectiveness and safety data were required to establish the long-term effectiveness and safety of ozanimod.⁶

To investigate the long-term safety and efficacy of extended ozanimod exposure, the DAYBREAK trial, an open-label extension trial of ozanimod was conducted.² Patients who completed the phase 1 RPC01-1001, phase 2 RADIANCE, phase 3 RADIANCE, or phase 3 SUNBEAM trials were eligible for the DAYBREAK trial, resulting in the enrollment of 2,494 patients who had received ozanimod 0.92 mg daily.² The mean exposure to ozanimod during the study was 60.9 months.²

Ozanimod demonstrated sustained efficacy with a low adjusted annual relapse rate (ARR) of 0.098 among all patients.² At months 60 and 72, 69% and 67% of participants were relapse-free, respectively.² In addition, the adjusted mean number of new or enlarging T2 lesions per scan at month 60 was low and similar across different parent trial groups.² Only 17.2% of participants had 3-month disability progression and 15.2% had 6-month disability progression within the DAYBREAK open-label extension period.²

Safety results were also evaluated in DAYBREAK, showing that ozanimod was generally well-tolerated.² A total of 89.0% of patients had treatment-emergent adverse events (TEAEs), of which 15.3% were serious, leading to 3.9% of patients discontinuing study drug due to a TEAE.² The rates of TEAEs were similar across the parent trial treatment groups.² Notably, 14.8% of patients had absolute lymphocyte counts <0.2x10⁹/L.² 1.8% had developed treatment-emergent malignancies and 64% of participants had an infection, of which 4.3% were serious.²

In conclusion, the DAYBREAK trial successfully investigated the long-term efficacy and safety of ozanimod. It found that ozanimod demonstrated sustained efficacy with low ARR, low numbers of new/enlarging lesions, and control of disease progression.² It was well-tolerated with a high percentage of patients completing the study.² The safety findings were consistent with previous studies and were able to establish the safety profile of ozanimod.²