Apitegromab Continues Positive Efficacy in SMA, Alzheimer Disease Risk Reduced Through Lifestyle Factors, Depressive Trajectories Predict Stroke Risk

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Welcome to this special edition of Neurology News Network. I’m Marco Meglio.

Recently announced 24-month results from the phase 2 TOPAZ trial showed that nonambulatory patients with types 2 and 3 spinal muscular atrophy (SMA) had sustained and continued improvement with apitegromab (SRK-015; Scholar Rock), a muscle-directed therapy, when used in conjunction with nusinersen (Spinraza; Biogen).1 Following 24 months of treatment with apitegromab, investigators documented a 4.0-point change in Hammersmith Functional Motor Scale Expanded (HFMSE), the primary end point, in the pooled ambulatory patient cohort, an increase from 3.6 points observed at the 12-month mark. Additionally, after excluding those with scoliosis surgery (n = 3), the mean change from baseline increased to 4.4 points (95% CI, 2.0-6.9) at the end of the 24-month period. "The 24-month results provide long-term data and evidence, underscoring the findings of the 12-month primary treatment period of the TOPAZ trial in which patients receiving apitegromab experienced sizable motor function gains," George Nomikos, MD, PhD, senior vice president of Clinical Sciences, head of Muscle Therapeutic Area, Scholar Rock, said in a statement.¹ "This durability and continued increase in motor function support the transformative potential of apitegromab for patients suffering with SMA."

A composite lifestyle score created using five factors—tobacco smoking, alcohol consumption, leisure-time physical activity (LTPA), sleep hours, and diet quality—showed that healthy lifestyles were associated with a reduced risk of Alzheimer disease and related dementias (ADRD), independent of sociodemographic factors and health conditions.1In a population-based cohort of mostly low-income Black and White Americans, individuals had each lifestyle factor scored as either 0 (unhealthy), 1 (intermediate), or 2 (healthy) based on health guidelines, with a composite score summing all scores. At the conclusion of the analysis, those with at least 7 points of the composite score (out of 10) showed a 32% reduced risk compared to those with 0 to 3 points. Similarly, those with 5 to 6 points had a 22% reduced risk as well. Although not necessarily a completely new finding, the study investigators, including senior author Danxia Yu, PhD, assistant professor, Vanderbilt School of Medicine, concluded that the data "support the impact of achievable, healthy lifestyles on preventing ADRD that could potentially benefit everyone to eventually reduce the health burdens and disparities posed by ADRD."

Findings from the Health and Retirement Study showed that those with depressive symptom trajectories characterized by consistently high symptoms are at an increased risk for stroke onset; however, decreasing symptom trajectories over time did not show an increased stroke risk. In the main analysis, compared with individuals with consistently low depressive symptoms—the reference group—individuals with consistently high depressive symptoms had a higher risk for incident stroke (adjusted HR, 1.18; 95% CI, 1.02-1.36). Similarly, individuals with increasing (adjusted HR, 1.31; 95% CI, 1.10-1.57) and fluctuating (adjusted HR, 1.21; 95% CI, 1.01-1.46) depressive symptoms had a higher risk for incident stroke compared with the reference group. In the study, no evidence of effect modification by sex, nor race and ethnicity, were observed on the interactions between depressive symptom trajectories and incident stroke.

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