The Food and Drug Administration (FDA) has approved Austedo (deutetrabenazine tablets; Teva) for the treatment of chorea associated with Huntington’s disease. Austedo, a vesicular monoamine transporter 2 (VMAT2) inhibitor, is the first deuterated product approved by the FDA.
The approval was based on a Phase 3 randomized, placebo-controlled trial which included 90 ambulatory patients (87 completed the study) with manifest chorea associated with Huntington’s disease. Treatment duration was 12 weeks, including an 8-week dose titration period and a 4-week maintenance period, followed by a 1-week washout. The primary efficacy endpoint was the Total Maximal Chorea Score, an item of the Unified Huntington’s Disease Rating Scale (UHDRS); chorea was rated from 0–4 (0 representing no chorea) and was scored for seven different parts of the body (range: 0–28).
Total Maximal Chorea Scores for patients receiving Austedo improved by approximately 4.4 units from baseline to the maintenance period (average of Week 9 and Week 12), compared to approximately 1.9 units in the placebo group. The treatment effect of –2.5 units was statistically significant (P<0.0001). At the Week 13 follow-up visit (1 week after discontinuation of the study medication), the Total Maximal Chorea Scores of patients who had received Austedo returned to baseline.
While the exact mechanism by which deutetrabenazine exerts its anti-chorea effects is unknown, it is believed to be related to its effect as a reversible depletor of monoamines (such as dopamine, serotonin, norepinephrine, and histamine) from nerve terminals. The major circulating metabolites (α-dihydrotetrabenazine [HTBZ] and β-HTBZ) of deutetrabenazine, are reversible inhibitors of VMAT2, resulting in decreased uptake of monoamines into synaptic vesicles and depletion of monoamine stores.
The prescribing information for Austedo includes a boxed warning regarding depression and suicidality. Clinicians should monitor patients for the emergence or worsening of depression, suicidality, or unusual changes in behavior and should use caution if treatment is being considered for those with a history of depression or prior suicide attempts. Austedo is contraindicated in patients who are suicidal, and in patients with untreated or inadequately treated depression.
Austedo will be supplied in 6mg, 9mg, and 12mg tablets in 60-count bottles. The product is expected to be available within the next three weeks.
For more information call (888) 483-8279 or visit TevaPharm.com.