Objective: To assess the motor and non-motor effects of mevidalen in patients with Lewy Body Dementia (LBD) as measured by the MDS-UPDRS.
Background: Mevidalen is a novel positive allosteric modulator of D1 receptor (D1PAM). D1 receptor activation improves cognitive and motor function and enhances wakefulness in preclinical and clinical models. The Phase 2, 12-week PRESENCE study was designed to evaluate the symptomatic effect of mevidalen for treatment of cognition and other domains relevant to LBD including motor function, sleep, mood and apathy.
Method: Participants (N=344) with LBD, aged 40-85 years, and with a Hoehn and Yahr score of 0-4 and a Montreal Cognitive Assessment score of 10-23 were randomized 1:1:1:1 to mevidalen 10 mg, 30 mg, or 75 mg, or placebo once-daily. The primary cognition outcome was CDR-CoA. Secondary outcomes included change from baseline to Week 12 in the MDS-UPDRS total score (sum of Parts I-III) and change in both the MDS-UPDRS Part II (motor experiences of daily living) and Part III (motor exam) scores. Analyses were also pre-specified for the Part I items of fatigue, daytime sleepiness, hallucinations, depressed mood and apathy, and the Part IV items of motor fluctuations and dyskinesias.
Results: While mevidalen did not improve the primary cognitive outcome, there was dose-dependent improvement in the MDS-UPDRS total score. Compared to placebo, least square mean changes for mevidalen 10, 30 and 75 mg were -6.58 (p=0.026), -7.56 (p=0.014) and -10.77 (p<0.001), respectively. There was a dose-dependent improvement in MDS-UPDRS Part II at the 30 and 75 mg doses (p=0.014 and p<0.001, respectively) and Part III, at the 75 mg dose (p=0.032). Individual item analysis revealed improvements in the Part I items of fatigue and daytime sleepiness at all doses, improvement in multiple items in Part II, improvement in the Part III bradykinesia items (all doses) and rigidity items (30 mg dose); and a dose-dependent worsening of dyskinesias items in Part IV, significant for mevidalen 75 mg.
Conclusion: Mevidalen, which harnesses a novel mechanism of action, resulted in symptomatic improvement of motor and select non-motor symptoms of parkinsonism associated with LBD, and avoided worsening of non-motor symptoms associated with traditional dopaminergic therapy.
To cite this abstract in AMA style:K. Biglan, L. Munsie, K. Svensson, P. Ardayfio, M. Pugh, J. Sims, M. Brys. Motor and non-motor effects of mevidalen in Lewy Body Dementia as measured by the Movement Disorder Society’s Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/motor-and-non-motor-effects-of-mevidalen-in-lewy-body-dementia-as-measured-by-the-movement-disorder-societys-unified-parkinsons-disease-rating-scale-mds-updrs/. Accessed December 7, 2023.
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MDS Abstracts - https://www.mdsabstracts.org/abstract/motor-and-non-motor-effects-of-mevidalen-in-lewy-body-dementia-as-measured-by-the-movement-disorder-societys-unified-parkinsons-disease-rating-scale-mds-updrs/