Long-Term Gains with Austedo in Tardive Dyskinesia

Deutetrabenazine (Austedo) showed maintained efficacy for tardive dyskinesia (TD) symptoms over a 3-year period, researchers reported.

In an open-label extension study of two 12-week clinical trials, 73% patients on deutetrabenazine maintained treatment success 3 years after initial dosing based on Clinical Global Impression of Change (CGIC), reported Robert Hauser, MD, MBA, of the University of South Florida Parkinson’s Disease and Movement Disorders Center in Tampa, Florida, at the virtual Psych Congress.

By the end of the first year, of the 249 that stayed on the drug at an average dose of 38.7 mg a day, the mean change from baseline in Abnormal Involuntary Movement Scale (AIMS) score was -4.8. This equated to a total of 66% of patients achieving “treatment success” — defined as “very much improved” or “much improved” on the CGIC.

And by the end of the second year, of the 194 patients that stayed on treatment — now at an average dose of 39.3 mg per day — the mean change from baseline AIMS score was -5.4 with 65% of these patients achieving success.

By the end of the third year, the 160 patients that stayed on deutetrabenazine at an average dose of 39.4 mg per day, the average drop in AIMS score was 6.6 with 73% experiencing treatment success. Additionally, 67% achieved an improvement of 50% or more in AIMS score, while 42% achieved a 70% or greater improvement.

“Overall, results from this analysis showed that patients with TD who received long-term treatment with deutetrabenazine achieved sustained improvement in AIMS score and treatment response rates that were indicative in clinically meaningful long-term benefits,” Hauser stated during an online presentation of the poster.

FDA approved for adults with TD in August 2017, deutetrabenazine works by inhibiting the vesicular monoamine 2 transporter (VMAT2) pathway involved in regulating dopamine levels in the brain. The treatment also holds another indication for the treatment of chorea association with Huntington’s disease.

For this single-arm, open-label extension study, any patients who participated in one of the two pivotal clinical studies could participate. Following a 1-week washout period, 337 patients were started on 12 mg per day and were then titrated to once per week for 6 weeks. This included 227 participants who previously received the study treatment in the clinical trial and 110 who had received placebo. The maximum dose of deutetrabenazine allowed was 48 mg per day or 36 mg per day for patients already receiving a strong CYP2D6 inhibitor.

At baseline, the average total motor AIMS score was 10.7 and 75% were receiving a dopamine-receptor antagonist.

In a related Psych Congress poster presentation, more data from the 3-year, open-label extension study showed that patients with a higher baseline AIMS score saw even greater treatment responses.

Looking again at the 337 in the post-hoc analysis, 273 had a baseline AIMS score of less than 14. On the other hand, 64 patients had an AIMS score of 14 or higher.

Comparing these two groups, those who had more severe TD movements at baseline saw an average 11-point drop in AIMS score by week 145 versus a drop of 5.1 points for those with less severe disease. This equated to an average 60.1% drop in AIMS score for those with baseline scores of 14-plus versus a 55.9% drop for those with baselines scores under 14.

By the end of the 3-year extension, 73% of those with more severe movements achieved a 50% or greater improvement in AIMS score versus 65% of those with less severe movements at baseline.

“Among patients with the most severe tardive dyskinesia movements, treatment with deutetrabenazine was associated with more robust and clinically meaningful reductions in AIMS score and a lower likelihood of withdrawal from the treatment,” said Nayla Chaijale, PhD, of Teva Pharmaceuticals in West Chester, Pennsylvania during an virtual oral presentation.

Disclosures

The study was funded by Teva Pharmaceutical Industries. Co-authors are company employees.

Hauser disclosed multiple relevant relationships with industry including Teva Pharmaceuticals. Co-authors disclosed multiple relevant relationships with industry.

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