Ozanimod Controls MS Disease Activity Regardless of Age

WEST PALM BEACH, Fla. — Clinical and radiologic measures of disease activity remained stable or improved for relapsing multiple sclerosis (RMS) patients in all age groups over 7 to 8 years of continuous treatment with ozanimod (Zeposia).

“Regardless of age category, the adjusted annualized relapse rate was below 0.2 in the phase III parent trials and remained low in the DAYBREAK open-label extension in patients treated with continuous ozanimod,” said Jeffrey Cohen, MD, of the Cleveland Clinic in Ohio, in a poster presentation at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) forum.

A total of 2,257 RMS patients in the parent SUNBEAM and RADIANCE trials participated in the open-label DAYBREAK extension study. By age category, the number of patients treated continuously with 0.92 mg ozanimod from the start of the phase III trials included 118 people ages 25 or younger, 268 people ages 26 to 35, 313 people ages 36 to 50, and 62 people ages 50 and older.

Patients continually taking ozanimod, an oral sphingosine 1-phosphate (S1P) receptor 1 and 5 modulator, had consistently lower rates of relapse and almost always had numerically lower rates of relapse than those who originally received interferon beta-1a before being switched to ozanimod, Cohen said.

“We also noted that even the patients who started the trial on interferon, when they switched to ozanimod in the open-label extension, they basically caught up to the people who were on ozanimod the entire length of the phase III trials and the extension,” he told MedPage Today.

There were similar relationships on age for the number of gadolinium-enhancing lesions, which averaged 0.6 per scan throughout the open-label extension, Cohen added. The number of new or enlarging T2 lesions per scan was reduced as patients got older, he said.

“This is something that has been observed in relapsing multiple sclerosis over time,” Cohen noted. A decline in these lesions may be part of declining immune activity as people age, he suggested. Long-term treatment also may interrupt the cascade of molecular inflammatory events that can cause nerve injury, he noted.

Ozanimod was approved to treat RMS in 2020 based on data from the pivotal SUNBEAM and RADIANCE studies, which showed lower relapse rates with ozanimod compared with interferon beta-1a. Patients who completed SUNBEAM and RADIANCE were eligible to enroll in the open-label extension of ozanimod 0.92 mg.

Cohen explained that while the relapses and appearance of new lesions remained low overall in the extension study, the team wanted to determine whether those rates diminished with age.

The findings should be reassuring to clinicians who are treating older patients with ozanimod for long durations, noted Patrick Vermersch, MD, PhD, of University Hospital Lille in France, who wasn’t involved with the study.

“When you treat long-term with these immune-modulating agents, there is always a concern that the risk of infections can occur, and the risk would be greater in an older patient,” Vermersch told MedPage Today. “We did not see this occur in patients in the DAYBREAK study.”

In a companion study presented at the meeting, Cohen and colleagues reported that the final analysis of the DAYBREAK extension study showed that treatment with 0.92 mg ozanimod controlled disease activity for longer than previously reported — a mean of 60.9 months, with some patients having been on treatment for 117.2 months (i.e., nearly 10 years).

“Ozanimod was generally well tolerated, with 78.2% of participants completing the study,” Cohen said. “Ozanimod demonstrated sustained efficacy with a low annualized relapse rate of 0.098, low numbers of new or enlarging T2 lesions of an average of less than 1 new or enlarging lesion per scan at 60 months, and mean number of gadolinium-enhancing lesions on brain MRI of an average of about 0.24 lesions per scan at 60 months.”

The safety findings were consistent with phase III trials and the established safety profile of ozanimod, Cohen noted.

“While we rarely would start a patient on interferons or glatiramer acetate these days but rather on disease-modifying agents, it is still good that we have this data to show there is an advantage to the use of these newer agents such as ozanimod,” he said.