FDA approves Austedo for Huntington’s chorea

The US Food and Drug Administration (FDA) has approved Austedo (deutetrabenazine) for the treatment of chorea associated with Huntington’s disease.

The drug, manufactured by Teva, is a deuterated form of tetrabenazine, a small molecule vesicular monoamine 2 transporter (VMAT2) inhibitor, which is already approved by the FDA for the same indication.

Austedo is the first deuterated product to be approved by the FDA. It contains a substituted “heavy hydrogen” isotope deuterium at two key locations in the molecule that result in it being metabolised more slowly and therefore lasting longer in the bloodstream and reducing variability in blood levels between patients.

Austedo’s efficacy was assessed in a randomised placebo-controlled trial involving 90 ambulatory patients with chorea associated with Huntington’s disease. Following eight weeks titration, the average chorea score on the Unified Huntington’s Disease Rating Scale during a four-week maintenance period was compared to baseline.

Results showed that total chorea scores (where the maximum score was 28) decreased by a mean of 4.4 points with Austedo versus 1.9 points with placebo.

The drug’s mechanism of action is thought to be related to decreasing the uptake of monoamines, such as dopamine and serotonin, into synaptic vesicles and depleting monoamine stores.

The most common adverse events in clinical trials were somnolence, diarrhoea, dry mouth, fatigue, urinary tract infection and insomnia. The prescribing information carries a boxed warning for depression and suicidality, due to an increased risk of these seen during clinical trials.

The FDA rejected Teva’s initial marketing application in May 2016, stating they needed additional information about certain blood metabolites seen in people who had taken the drug.

The FDA accepted a resubmitted application in October 2016.