Highlights from

AAN 2019

American Academy of Neurology annual meeting

Philadelphia, USA 4-10 May 2019

T-type-calcium channel modulator in essential tremor

A randomised study achieved proof-of-concept for CX-8998 in essential tremor. Key pivotal study design parameters including primary and secondary efficacy endpoints, patient population, dose and titration scheme, were identified [1]. Further studies are needed to evaluate its efficacy.

CX-8998 is a potent, selective, and state-dependent small molecule modulator of T-type calcium channels. T-type calcium channels play a critical role in the generation of tremor-related oscillations. CX-8998 was evaluated in a double-blind, placebo-controlled study of 95 patients with moderate to severe essential tremor who had inadequate response to standard of care anti-tremor medications. They were randomised to either CX-8998 (titrated to 10 mg BID) or placebo for 28 days. The study's primary endpoint was centrally video-rated TETRAS (The Essential Tremor Rating Assessment Scale) Performance Subscale.

Due to methodological issues this endpoint did not reach significance in the CX-8998 group. However, there were significant improvements in investigator-rated TETRAS Performance Subscale (P=0.017), TETRAS-ADL (Activities of Daily Living; P=0.049), TETRAS total score (P=0.007), and Clinician Global Impression of Improvement (P=0.001). The significant differences on TETRAS-ADL were confirmed by Goal Attainment Scaling (P=0.034) and supported by the Patient's Global Impression of Change (P=0.089). In a subset of patients, digital spirography using an app that measures and monitors motor performance was qualified as a digital marker.

  1. Papapetropoulos S, et al. AAN 2019, S4.008.

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