S1P Receptor Modulator May Boost Cognitive Processing Speed in Early MS

Treatment with ozanimod (Zeposia) led to clinically meaningful improvement in cognitive processing speed among people with early relapsing multiple sclerosis (RMS), an ad hoc interim analysis of the phase IIIb ENLIGHTEN trial showed.

After 1 year, nearly half — 47.4% — of early RMS patients had an increase of at least 4 points or 10% from baseline in Symbol Digital Modalities Test (SDMT) scores, reported Robert Naismith, MD, of Washington University in St. Louis, in a poster presentation at the joint meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and the American Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).

Nearly a quarter (25.9%) of study participants remained stable in their cognitive function, and a quarter (26.7%) worsened, defined as a decrease of at least 4 points or 10% in SDMT scores from baseline.

“Cognitive dysfunction occurs early in MS, and is one of the most disabling symptoms,” Naismith told MedPage Today. “The ability of disease-modifying therapies to stabilize or improve cognition is important for maintaining quality of life for our patients.”

Ozanimod, an oral sphingosine-1-phosphate (S1P) receptor modulator, was approved to treat RMS in 2020, based on data from the pivotal SUNBEAM and RADIANCE studies comparing ozanimod against interferon beta-1a (Avonex). The drug also is approved to treat ulcerative colitis.

In SUNBEAM, ozanimod 0.92 mg improved SDMT scores — a component of a secondary endpoint — compared with interferon.

“Based on the encouraging results of ozanimod on cognitive processing speed in the phase III SUNBEAM trial, the Symbol Digit Modalities Test was further explored as a primary endpoint in ENLIGHTEN,” Naismith noted. “The 3-year ENLIGHTEN study includes patients diagnosed very recently, as we know cognitive complaints begin early in MS.”

ENLIGHTEN is an ongoing single-arm efficacy and safety study of 185 people with early RMS who received one or more doses of ozanimod 0.92 mg. The trial started in January 2020 and data cutoff was February 2023.

The primary endpoint was the proportion of patients with an increase in SDMT score of at least 4 points or 10% from baseline. The SDMT is a series of symbol/digit substitution tasks; participants must match the appropriate symbol to the paired numerical digit using a key. Scores depend on the correct number of responses given in 90 seconds, with higher scores indicating faster cognitive processing speed.

The SDMT was administered orally in ENLIGHTEN. A change of 4 or more points on the SDMT is considered clinically important.

At baseline, mean age was 39.5 and 78% of participants were female. Most (86%) were white and 11% were Black. Mean years since MS symptom onset was about 4 years, and 70.3% had not previously been treated with a disease-modifying therapy.

Median Expanded Disability Status Scale (EDSS) score was 2 at baseline, and mean SDMT score was 53.9. About a third of participants were relapse-free in the previous 12 months.

ENLIGHTEN participants had little clinical or radiologic evidence of disease activity during the first year of ozanimod treatment. The annualized relapse rate was 0.2 (95% CI 0.1-0.4), and 91.9% of patients were free of gadolinium-enhancing lesions at month 12 (95% CI 84.2%-96.0%).

COVID-19 was the most frequent treatment-emergent adverse event through February 2023, with other adverse events largely consistent with those reported in the phase III ozanimod studies.

“The results suggest that ozanimod may improve cognitive processing speed in nearly half of patients when initiated in early relapsing multiple sclerosis,” Naismith noted. “It will be interesting to see how these patients do over longer intervals as more data become available.”

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