SAN DIEGO — Ozanimod was associated with stable or improved cognition in nearly 90% of patients who received the drug for relapsing-remitting multiple sclerosis (RRMS), a new study showed.

Results from the multicenter phase 3b trial found that 60% of patients had improved cognitive scores after 3 years of treatment compared with baseline. Of the remaining cases, about 28% showed stable cognitive function after treatment, and only 12% saw a decline.

Investigators said that’s important since about half of people with RRMS have cognitive decline upon diagnosis.

“You would expect about a third of individuals over a 3-year period to get worse. That’s a pretty significant difference,” lead investigator John DeLuca, PhD, senior vice president for Research and Training, Kessler Foundation, West Orange, New Jersey, told Medscape Medical News.

The findings were presented on February 5 at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2026.

Challenges of Decline in Cognition

Patients with RRMS often see declines in information processing speed, verbal learning, and visuospatial memory early in the disease process. These cognitive changes affect communication, attention, executive function — such as the ability to follow directions and complete tasks — and memory formation.

Previous studies have shown that those impairments in cognitive functioning are associated with a reduction in employment and decreased quality of life.

Despite the prevalence of cognitive impairment, no therapy is currently approved specifically to treat the condition in MS, noted DeLuca, who is also a professor of neurology at Rutgers New Jersey Medical School in Newark, New Jersey.

Ozanimod is an oral, second-generation sphingosine 1-phosphate receptor that can cross the blood-brain barrier. As previously reported by Medscape Medical News, 70% of patients treated with ozanimod remained relapse-free after 5 years of treatment.

The single-arm, longitudinal, open-label ENLIGHTEN trial evaluated changes in cognitive function after treatment with ozanimod. Researchers presented data following 1 year of treatment at ACTRIMS 2025. The new data include analysis of patients through year 3.

For the study, researchers recruited 188 patients aged 18-65 years (average age, 39.5 years; 78.7% female; 85.6% White, 10.6% Black; 11.2% Latino/Hispanic).

Participants had RRMS, ≤ 1 disease-modifying therapy (none within 1 month of enrollment), an Expanded Disability Status Scale score ≤ 3.5 at screening, no relapses within 30 days prior to screening, and ≤ 10 gadolinium-enhancing lesions on a baseline brain MRI scan.

Patients were placed on a 7-day dose escalation schedule, with 0.23 mg/d on days 1-4, 0.46 mg/d on days 5-7, and 0.92 mg/d from day 8 on.

Cognitive function was assessed with the Symbol Digit Modalities Test (SDMT), California Verbal Learning Test-Second Edition, and Brief Visuospatial Memory Test-Revised (BVMT-R).

Stable and Improved Cognition

Ozanimod was associated with preserved cognitive function on all three measures.

SDMT mean scores improved from 53.4 to 59.4 at 3 years (mean SD change, 14.7%; least squares [LS] mean change, 4.5).

Scores on the CLVT-II increased from 52.9 to 59.4 at 3 years (mean SD change, 13.2%; LS mean change, 5.2), while BVMT-R scores changed from 24.3 at baseline to 24.1 at 3 years (mean SD change, 3.5%; LS mean change, -0.7).

At 3 years, a total of 88% of participants had either improved or remained stable on the SDMT, and 59.6% had higher scores than they did when they started treatment.

Improved was defined as a ≥ 4-point or ≥ 10% increase relative to baseline; stable was a change from baseline between -4 and 4 points and a percentage change between -10% and 10%; and worsened was a ≥ 4-point or ≥ 10% decrease relative to baseline.

In a related study presented at ACTRIMS Forum 2026, also co-authored by DeLuca, brain volume tracked in ENLIGHTEN participants. Researchers found that annualized rates of brain volume loss were similar to healthy controls.

“If your patient early in disease is already showing cognitive problems — and especially if they’re showing problems on MRI, particularly gray matter volume loss — that should be a sign to say, ‘I need to be more aggressive,’” DeLuca said.

“Ozanimod has been shown to actually decrease the loss of brain volume and maintain cognitive function. So it could be one potential way to help patients who are at risk,” he added.

Limited, but Helpful

Commenting on the findings, Patricia K. Coyle, MD, professor and director of the Multiple Sclerosis Comprehensive Care Center, Stony Brook University, Stony Brook, New York, noted that the cognitive tests used in the cognition trial are brief and not comprehensive.

“These tests take like 10-15 minutes,” she told Medscape Medical News. “In in-depth cognitive function testing, you might go an hour, you might go 4 hours.”

She also noted that the SDMT, while widely used, is “falling out of favor” as a stand-alone measure, which makes the addition of the other two tests helpful.

The study’s biggest limitation, Coyle said, is the absence of a control group.

Still, the study is “a little bit of support for ozanimod. You choose your disease-modifying therapy in a context of a number of factors, but it’s a good thing to know that it was associated over 3 years with cognitive stabilization,” Coyle said.

Bristol Myers Squibb funded both studies. DeLuca disclosed having relationships with Biogen, Bristol Myers Squibb, Janssen, Novartis, the Consortium of Multiple Sclerosis Centers, EMD Serono, the Canadian Multiple Sclerosis Society, Genentech, National Institutes of Health, and the National Multiple Sclerosis Society. Coyle disclosed having multiple relationships with pharmaceutical companies, including Bristol Myers Squibb.