Ozanimod Shows Long-Term Safety, Efficacy in Open-Label Extension

September 18, 2020
Marco Meglio
Marco Meglio

Marco Meglio, Associate Editor for NeurologyLive, has been with the team since October 2019. Follow him on Twitter @marcomeglio1 or email him at mmeglio@neurologylive.com

Along with being generally well tolerated, ozanimod was able to help most patients become relapse free without disability progression.

Interim analysis from an open-label extension of patients with relapsing forms of multiple sclerosis (RMS) enrolled in the DAYBREAK study (NCT02576717) showed an association between ozanimod (Zeposia; Bristol Myers Squibb) and low annualized relapse rate (ARR) and low counts of new or enlarging T2 and gadolinium-enhancing (GdE) lesions over time.1

Presented at MS Virtual 2020, the 8th Joint ECTRIMS-ACTRIMS meeting, September 11–13, 2020, senior author Bruce Cree, clinical research director, UCSF Multiple Sclerosis Center, and professor of clinical neurology, USCF Weill Institute for Neurosciences, and colleagues aimed to characterize the long-term safety and efficacy of ozanimod in patients with RMS in this ongoing open-label extension trial.

At Months 24 and 36, 79% and 75% of participants, respectively, were relapse free. A cohort of 2492 participants with a mean ozanimod exposure of 35.4 months (range, 0.03–50.2) revealed an adjusted ARR of 0.112 (95% CI, 0.093–0.135).

Participants within the trial were eligible if they had completed any phase 1, 2, or 3 trial of ozanimod previously. Investigators calculated number of new/enlarging T2 and GdE magnetic resonance imaging (MRI) brain lesions for the subset of patients who entered the open-label extension from an active-controlled phase 3 trial.

Regardless of parent-trial treatment group mean number of new/enlarging T2 lesions per scan at 24 hours was similar (range, 1.57–1.90), as well as the mean number of GdE lesions at month 24 (range, 0.2–0.4). Confirmed disability progression (CDP) was observed in 10.8% and 8.6% of participants at 3- and 6-months, respectively.

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Available data on safety measures from 2039 participants showed that 81.8% of the population had a treatment-emergent adverse event (TEAE). Additionally, 9.5% of patients had a serious TEAE (SAE) and 56 (2.2%) discontinued due to a TEAE. Researchers also noted that similar rates of TEAEs and SAEs occurred when assessed by the parent-trial treatment group.

Nasopharyngitis (17.9%), headache (14%), upper respiratory tract infection (9.9%), and lymphopenia (9.6%) were among the most common TEAEs observed within the extension period. There were no serious opportunistic infections and exposure-adjusted incidence rates of TEAEs and SAEs decreased over time.

Ozanimod, an oral sphingosine 1-phosphate (S1P) receptor modulator was approved by the FDA for the treatment of adults with RMS, including clinically isolated syndrome, relapsing-remitting MS, and active secondary progressive MS in March.2

The approval of ozanimod was based off data from the phase 3 SUNBEAM (NCT02294058) and RADIANCE part B (NCT01628393) trials that included more than 2600 adults. The randomized, active-controlled studies compared ozanimod to interferon beta-1a (IFNß1a; Avonex) on the primary end point of ARR.

Bristol Myers Squibb announced the commercial launch and availability of ozanimod in June, making it the first and only S1P on the market that required no first dose observation.3

1. Selmaj K, Steinman L, Comi G, et al. Long-term safety and efficacy of ozanimod in relapsing multiple sclerosis in DAYBREAK: an open-label extension study of ozanimod phase 1–3 trials. Presented at MS Virtual 2020 Joint ECTRIMS-ACTRIMS meeting; September 11–13, 2020. Abstract P0217.
2. U.S. Food and Drug Administration Approves Bristol Myers Squibb’s ZEPOSIA® (ozanimod), a New Oral Treatment for Relapsing Forms of Multiple Sclerosis [news release]. Briston Myers Squibb Company. March 26, 2020. finance.yahoo.com/news/u-food-drug-administration-approves-103000096.html
3. Bristol Myers Squibb Announces Commercial Launch and Availability of ZEPOSIA® (ozanimod), a New Oral Treatment for Relapsing Forms of Multiple Sclerosis [news release]. Princeton, NJ; Published June 1, 2020. Accessed June 8, 2020. news.bms.com/press-release/corporatefinancial-news/bristol-myers-squibb-announces-commercial-launch-and-availabil