A proof‐of‐concept study with SOM3355 (bevantolol hydrochloride) for reducing chorea in Huntington's disease

Aims The study's aim is to investigate the efficacy and safety of SOM3355 (bevantolol hydrochloride), a β1‐adrenoreceptor antagonist with recently identified vesicular monoamine transporter type 2 inhibitory properties, as a repositioned treatment to reduce chorea in Huntington's disease (HD). Methods A randomized, placebo‐controlled proof‐of‐concept study was performed in 32 HD patients allocated to 2 arms of 4 sequential 6‐week periods each. Patients received placebo and SOM3355 at 100 and 200 mg twice daily in a crossover design. The primary endpoint was improvement by at least 2 points in the total maximal chorea score in any active drug period compared with the placebo period. Results The primary endpoint was met in 57.1% of the patients. Improvements ≥3, ≥4, ≥5 and ≥6 points vs. placebo treatment were observed in 28.6, 25.0, 17.9 and 10.7% of the patients, respectively. A mixed‐model analysis found a significant improvement in the total maximal chorea score of −1.14 (95% confidence interval, −2.11 to −0.16; P = .0224) with 200 mg twice daily SOM3355 treatment compared with placebo treatment. These results were paralleled by Clinical and Patient Global Impression of Change ratings (secondary endpoints). An elevation in plasma prolactin levels by 1.7–1.9‐fold was recorded (P