#ECTRIMS2018 – Additional Analysis on Ozanimod Demonstrates Its Potential to Treat Relapsing MS

Additional analysis of clinical data from Celgene’s investigational agent ozanimod continues to demonstrate its potential to benefit patients with relapsing multiple sclerosis (MS).

Findings from the Phase 3 SUNBEAM and RADIANCE Part B trials were discussed at the 34^th Congress of the European Committee for Treatment and Research In Multiple Sclerosis (ECTRIMS), held Oct. 10-12, in Berlin, Germany.

Ozanimod is an orally available compound designed to inhibit the migration of immune cells involved in inflammatory processes that promote damage to nerve fibers and to the myelin sheaths that protect them — a hallmark of MS).

The SUNBEAM study (NCT02294058) enrolled 1,346 patients with relapsing MS, who were randomized to receive once-daily 0.92 or 0.46 mg ozanimod  — equivalent to 1 mg and 0.5 mg ozanimod HCI formulation  — or once-weekly intramuscular injection of the approved therapy Avonex (interferon beta-1a, marketed by Biogen), for at least 12 months.

Previous results showed that ozanimod could reduce the relapse rate and the number of brain lesions in these patients.

Now, a post-hoc analysis of the data revealed that treatment with ozanimod for a year could promote significant changes in patients’ cognitive processing speed, compared to Avonex.

Ozanimod-treated patients showed a 1.6-point change and a 1.2-point change with 1 mg and 0.5 mg of the drug, respectively, in cognitive processing speed, as determined through the Symbol Digit Modalities Test (SDMT).

Also, more patients experienced clinically meaningful improvements in processing speed (assessed as a four-point or higher improvement in SDMT score) upon treatment with ozanimod than with Avonex after a year of treatment.

“Slowed cognitive processing, which is common in multiple sclerosis, often impairs quality of life for people living with this chronic condition,” Bruce Cree, MD, PhD, professor at the University of California San Francisco (UCSF) Weill Institute for Neurosciences and researcher of the study, said in a press release.

“The findings from these new analyses suggest that, when compared to interferon [Avonex], ozanimod has a beneficial effect on processing speed,” said Cree, also clinical research director at the UCSF MS Center.

The results were presented at ECTRIMS 2018 in the poster presentation “Ozanimod-treated patients exhibited improvements in cognitive processing speed in the phase 3 SUNBEAM trial of relapsing multiple sclerosis (RMS).”

The potential of this investigational therapy was also evaluated in patients with relapsing-remitting multiple sclerosis (RRMS) in the two-part pivotal RADIANCE (NCT02047734) trial.

Researchers have now reviewed the effects of ozanimod based on pooled clinical data from both SUNBEAM and RADIANCE part B trials. The new analysis covered 2,659 patients with relapsing MS who were treated with once-daily 1 or 0.5 mg ozanimod, or once-weekly Avonex, for one to two years.

Results showed that treatment with higher and lower doses of ozanimod reduced by 42% and 26%, respectively, the annualized relapse rates compared to Avonex.

While approximately 96% of the confirmed relapses required steroid treatment or hospitalization, treatment with the investigational agent was found to reduce relapse rates requiring such approach by 43% (1 mg) and 26% (0.5 mg) in relation to Avonex.

In addition, the proportion of ozanimod-treated patients with relapses requiring steroids or hospitalization was of 20.1% and 23.3% in the higher- and lower-dose groups, whereas in the Avonex group was of 30.7%.

“These data support the potential of ozanimod as an effective oral treatment to reduce the rate of relapse, including severe relapse, in patients with relapsing MS,” researchers wrote.

In addition, in a total of 1,392 patients with early relapsing MS, data revealed that treatment with ozanimod efficiently reduced annualized relapse rates (0.149 in 1-mg group, and 0.200 in 0.5-mg group), compared with Avonex (0.285).

Ozanimod also significantly reduced the number and prevented the occurrence of new magnetic resonance imaging (MRI)-detectable brain lesions in early relapsing MS patients.

The mean number of brain lesions after one year were reduced in patients treated with ozanimod (0.263 in the 1-mg group, and 0.458 with 0.5 mg), compared with Avonex (0.656). Also, the count of enlarged or new lesions was found to have been reduced in both tested doses (2.952 in the 1-mg group, and 3.744 with 0.5 mg), compared with Avonex (4.633).

Similar effects were seen in patients with more advanced disease.

These findings were reported in two presentations at ECTRIMS titled “Ozanimod reduces rates of annualised relapse requiring steroids or hospitalisation versus interferon β-1a: pooled results from two multicentre, randomised, double-blind, phase 3 studies in relapsing multiple sclerosis (SUNBEAM and RADIANCE),” and “Impact of ozanimod on early and advanced relapsing multiple sclerosis: annualised relapse rate and MRI endpoints from two randomised, multicentre, double-blind, Phase 3 studies (SUNBEAM and RADIANCE).”

Together, “these analyses provide additional encouraging data for ozanimod in relapsing MS, from its potential to influence cognitive processing to showing results in patients with either early or more advanced forms of the disease,” said Jay Backstrom, MD, chief medical officer for Celgene.

“Ozanimod has the potential to offer the MS community a new oral option for the treatment of relapsing multiple sclerosis, and we continue to work with regulatory bodies in the U.S. and E.U. in our efforts to bring this treatment to patients,” Backstrom said.

Earlier this year, Celgene announced that the U.S. Food and Drug Administration requested more information to accept the new drug application submitted by the company for ozanimod as a treatment for relapsing MS.