Sustained efficacy and safety of ozanimod demonstrated in the DAYBREAK open-label extension study

09 May 2024

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

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