Non-Whites Underrepresented in MS DMT Trials, Stroke Risk in PD-Related Genes, Phase 2a ADv Study Initiated

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This week Neurology News Network covered a study that discussed the lack of non-White patients with MS in pivotal DMT trials, genetically associated vascular risks in patients with Parkinson disease, and the initiation of the phase 2a ADv study, which will evaluate the investigational agent CY6463 in patients with Alzheimer disease with vascular pathology.

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

Despite the documented differences in disease course and outcomes between White people with multiple sclerosis (PWMS) and Black and Hispanic PWMS, a systematic review of phase 3 trials for FDA-approved disease-modifying therapies (DMTs) showed that data specific to these groups were heavily underreported in these settings. When data was available for race or ethnicity, non-White PWMS were significantly underrepresented. Senior author Leorah Freeman, MD, PhD, and colleagues aimed to evaluate representation of non-White groups in phase 3 trials by combing through PubMed’s database from 1995 to June 2020. A total of 44 phase 3 trial publications, representing 45 trials that were pivotal in the clinical pathway of a chosen FDA-approved DMT, were reviewed. Of the studies identified, 37.8% (n = 17) did not report data related to race or ethnicity and 31.1% (n = 14) only reported race and ethnicity as a percentage of White participants only. Furthermore, only 31.1% (n = 14) reported the racial and ethnic breakdown of its participants using 2 or more races. Investigators also found that none of the patient- or healthcare professional (HCP)-facing websites reported information on race and ethnic representation in their pivotal trial results sections.

Research examining genetically associated vascular risks among patients with Parkinson disease (PD) showed that those with LRRK2-associated PD were at a significantly increased risk of ischemic stroke as well as represented the highest proportion of strokes among other PD-related genes. Previously, it had been documented that PD was associated with an increased stroke risk, however, there were limited data on whether this varied among specific PD-related genes. Using multivariate logistic regression and Cox regression analyses that controlled for sex, age, and vascular risk factors, the prevalence of ischemic stroke differed among groups. Despite no differences in coronary artery disease (CAD), the LRRK2-PD represented the highest cases of stroke (13.8%), followed by PRKN-PD (8.6%) and sPD (5.6%). Relative to controls, LRRK2-PD had a significantly increased risk of stroke, compared to other PD cohorts, where no difference was observed.

Patient dosing has begun for the randomized, placebo-controlled phase 2a ADv study evaluating CY6463, an investigational central nervous system (CNS)-penetrant agent developed by Cyclerion, in patients with Alzheimer disease with vascular pathology. Approximately 30 participants with a confirmed AD pathology will be randomized to either oral once-daily CY6463 or placebo over a 12-week dosing period. Investigators will assess safety, tolerability, and pharmacokinetics, as well as explore the agent’s impact on various disease-relevant pharmacodynamic biomarkers and cognitive performance. Patients included in the study must be 65 years of age or older, have Mini-Mental State Examination score of 20-26, and have at least 2 cardiovascular risk factors. Additionally, eligible patients have had findings of mild-to-moderate subcortical small-vessel disease on MRI scan and have not changed their concomitant or chronic medications for at least 4 weeks prior to receiving CY6463.

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