Category: Huntington's Disease
Objective: Proof-of-concept phase IIa study assessing bevantolol (SOM3355) efficacy and safety in reducing chorea in Huntington’s disease (HD).
Background: Bevantolol hydrochloride, a β1‐adrenoceptor antagonist used in hypertension, was identified by artificial intelligence screening among potential candidates as a vesicular monoamine transporter type 2 (VMAT2) inhibitor. Bevantolol was selected by in vitro functional studies to be repositioned to treat dyskinetic movements such as chorea in HD.
Method: A double-blind, randomized, crossover, placebo-controlled study was conducted in 32 patients with HD, who were randomly assigned to 2 arms of 4 sequential 6-week periods, in which they received placebo and bevantolol at 100 and 200 mg BID in a crossover design. The primary endpoint was defined as improvement of at least 2 points in the total maximal chorea (TMC) sub-score of the Unified Huntington’s Disease Rating Scale (UHDRS) in any active drug period compared with the placebo period.
Results: More than half of the patients (57.1%) had improvements in the TMC score of at least 2 points compared with placebo in any period with bevantolol, thus reaching the primary endpoint. Even more clinically significant TMC improvements of 3, 4, 5, and 6 points compared with placebo were seen with bevantolol in 28.6%, 25.0%, 17.9%, and 10.7% of the patients, respectively. Mixed-model analysis comparing the different periods showed significant improvement in the TMC score with bevantolol 200 mg BID compared with placebo (P = 0.0224), as confirmed in ratings of Clinical Global Impression of Change (CGIC) and Patient Global Impression of Change (PGIC). Mild elevations in plasma prolactin levels were recorded with bevantolol (P < 0.005), consistent with the profile of VMAT2 inhibition. Bevantolol was well tolerated with only mild or moderate adverse events, most of them expected due to the β1‐adrenoceptor antagonist effects on the cardiovascular system.
Conclusion: This study confirms that bevantolol reduces chorea in patients with HD and has a good safety profile.
To cite this abstract in AMA style:
J. Gamez, M. Calopa, E. Muñoz, A. Ferré, O. Huertas, K. Mcallister, N. Reig, C. Scart-Grès, R. Insa, J. Kulisevsky. Proof-of-concept study testing bevantolol (SOM3355) as treatment of chorea in Huntington’s disease [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/proof-of-concept-study-testing-bevantolol-som3355-as-treatment-of-chorea-in-huntingtons-disease/. Accessed June 15, 2025.« Back to MDS Virtual Congress 2021
MDS Abstracts - https://www.mdsabstracts.org/abstract/proof-of-concept-study-testing-bevantolol-som3355-as-treatment-of-chorea-in-huntingtons-disease/