The FDA has given the nod to deutetrabenazine (Austedo, Teva Pharmaceutical Industries) for the treatment of patients with chorea associated with Huntington’s disease (HD). Deutetrabenazine is a vesicular monoamine transporter 2 (VMAT2) inhibitor for oral administration that binds to melanin-containing tissues. It is the first new treatment for Huntington’s chorea in almost a decade.
The FDA’s approval was based on results from a phase 3, randomized, placebo-controlled study that assessed the safety and efficacy of deutetrabenazine in reducing chorea in 90 ambulatory patients with HD.
Total Maximal Chorea Scores (TMCSs) for patients receiving deutetrabenazine improved by approximately 4.4 units from baseline to the maintenance period (the average of week 9 and week 12) compared with approximately 1.9 units in the placebo group. This treatment effect of –2.5 units was statistically significant (P < 0.0001). The maintenance endpoint was the mean of the TMCSs for the week-9 and week-12 visits. At the week-13 follow-up visit (one week after discontinuation of the study medication), the TMCSs of patients who had received deutetrabenazine returned to baseline.
The precise mechanism by which deutetrabenazine exerts its antichorea effects is unknown but is believed to be related to its effect as a reversible depleter of monoamines (such as dopamine, serotonin, norepinephrine, and histamine) from nerve terminals. The major circulating metabolites of deutetrabenazine are reversible inhibitors of VMAT2, resulting in reduced uptake of monoamines into synaptic vesicles and depletion of monoamine stores.
The labelling for deutetrabenazine includes a boxed warning regarding the potential for depression and suicidality.
A rare and fatal neurodegenerative disorder, HD affects more than 35,000 people in the United States. Chorea––involuntary, random, and sudden twisting and/or writhing movements––is one of the most striking physical manifestations of the disease and occurs in approximately 90% of patients.