Austedo (deutetrabenazine) for the Treatment of Chorea, United States of America
Austedo™ (deutetrabenazine) is a vesicular monoamine transporter 2 (VMAT 2) inhibitor indicated for the treatment of chorea associated with Huntington's disease. The drug was discovered and developed by Teva Pharmaceutical Industries.
Teva's new drug application (NDA) for Austedo was accepted for review by the US Federal Drug Administration (FDA) in August 2015. Teva received a complete response letter (CRL) from the FDA to examine the blood levels of certain metabolites in the patients.
Teva resubmitted the NDA in October 2016 and received a Prescription Drug User Fee Act (PDUFA) goal date set for 3 April 2017.
FDA finally approved Austedo, the first deuterated product, in April 2017 and also gave orphan designation to the drug.
Teva plans to launch Austedo in the US market by the end of April 2017.
Huntington's disease (HD) is an unusual and inherited fatal neurodegenerative disorder that is caused by the death of nerve cells in the brain. Chorea is an involuntarily movement that occurs in 90% of HD patients, affecting their daily functionality and living activities.
The rare disorder affects movement, behaviour and cognition, while its early signs and symptoms include irritability, depression, small involuntary movements, trouble learning new information, and making decisions. It is estimated to affect more than 35,000 people in the US.
Austedo's mechanism of action
Austedo contains vesicular monoamine transporter 2 (VMAT 2) inhibitor, which works as reversible depletor of monoamines, including dopamine, serotonin, norepinephrine and histamine from the nerve terminals. It regulates the levels of dopamine, a neurotransmitter in the brain, and decreases the uptake of monoamines into synaptic vesicles and depletion of monoamine stores.
The drug is available in the form of tablets for oral administration.
Clinical trials on Austedo for Huntington's disease
The NDA filing for FDA Austedo was based on results obtained from two phase III clinical studies known as First-HD and ARC-HD. Results from First-HD, a placebo-controlled, randomised study, showed that chorea was reduced in HD patients treated with Austedo.
Results from ARC-HD, an open-label study, demonstrated that patients were able to safely convert from tetrabenazine, an approved HD treatment, to Austedo overnight with continued control of chorea.
FDA approval for the drug was based on the results obtained from the First-HD phase III clinical trial, which was a randomised, double-blind, placebo-controlled, multi-centre study. The study involved a total of 90 ambulatory patients suffering from manifest chorea associated with first HD, including 45 Austedo and 45 placebo patients. The trial continued for 12 weeks.
Study results demonstrated that patients treated with Austedo improved 4.4 units of maximal chorea scores from baseline to the maintenance period, compared to 1.9 units in the placebo group at week 12. The total maximum chorea scores of patients who had received Austedo at the week 13 follow-up visit retuned to baseline.
The most common adverse reactions found in the clinical study in patients administered with Austedo were somnolence, diarrhoea, dry mouth and fatigue.
Clinical trials on Austedo for other indications
Teva has conducted clinical trials on Austedo for the treatment of other indications, including moderate to severe tardive dyskinesia, and tics associated with Tourette syndrome.
FDA selected Austedo for the breakthrough treatment of tardive dyskinesia in November 2015 based on the results obtained from ARM-TD clinical study, which was a randomised, double-blind, placebo-controlled, parallel-group study.
The study involved 117 patients with moderate to severe tardive dyskinesia.