FDA Approves Extended-Release Deutetrabenazine for Huntington Disease Chorea, Tardive Dyskinesia

Article

Teva’s VMAT2 inhibitor was previously approved in a twice-daily formulation. The once-daily extended-release treatment, marketed as Austedo XR, is expected to be available later in 2023 in doses of 6 mg, 12 mg, and 24 mg.

Eric Hughes, MD, PhD, executive vice president of R&D and chief medical officer at Teva

Eric Hughes, MD, PhD

The FDA has given the go-ahead to deutetrabenazine (Austedo XR; Teva Pharmaceuticals) in a once-daily, extended-release formulation for the treatment of adults with tardive dyskinesia (TD) and chorea associated with Huntington disease (HD).1 Teva announced that the new formulation of the previously approved twice-daily therapy is anticipated to become available some time in 2023.

“The approval of Austedo XR is a reflection of our ongoing innovation for people living with TD and HD chorea,” Eric Hughes, MD, PhD, executive vice president of R&D and chief medical officer at Teva, said in a statement.1 “For some patients living with TD and HD, treatment adherence can be a challenge that this new once-daily dosing option can help to address.”

Deutetrabenazine is a vesicular monoamine transporter 2 (VMAT2) inhibitor with 3 years’ worth of data for both indications. In October 2022, Teva announced the findings from its phase 3 open-label, single-arm, 2-cohort, multicenter, ARC-HD extension study (NCT01897896) which demonstrated that treatment with deutetrabenazine was safe and improved and maintained chorea in patients with HD over a 3-year treatment period.2,3

Treatment with deutetrabenazine resulted in a mean Total Maximal Chorea (TMC) score decrease of –4.5 points (SD, 3.1; 95% CI, –5.2 to –3.7) for those who completed the double-blind First-HD trial (NCT01795859), termed the rollover cohort (n = 82), and a decrease of –2.1 points (SD, 3.3; 95% CI, –3.1 to –1.0) for those who converted overnight from a stable tetrabenazine dose (switch arm, n = 37) from baseline to week 8. In both the rollover and switch cohorts, mean motor scores decreased from baseline by –7.1 points (SD, 7.3; 95% CI, –8.8 to –5.5) and –2.4 points (SD, 8.7; 95% CI, –5.4 to 0.5), respectively.2,3

ARC-HD lead investigator Samuel Frank, MD, an associate professor of neurology and director of the HDSA Center of Excellence at Beth Israel Deaconess Medical Center, said in a statement2 at the time that, "These data provide important insight into the long-term use of deutetrabenazine for the treatment of chorea associated with Huntington’s disease, which can have a significant functional impact on people’s lives. Results of this study add to the safety and tolerability profile and support deutetrabenazine as a treatment choice for this progressive condition."

Similarly, in August 2021, the findings of a 3-year post hoc analysis of patients who completed the ARM-TD or AIM-TD studies (NCT02195700; NCT02291861) showed that long-term treatment with deutetrabenazine was well-tolerated and associated with sustained improvement in total motor Abnormal Involuntary Movement Scale (AIMS) score, treatment success, and improved quality of life in both older and younger patients with tardive dyskinesia (TD).4

At the conclusion of the 3-year period, both the younger (n = 119; <55 years) and older (n = 218; ≥5 years) subgroups experienced reductions of –6.7 points (standard error [SE], 0.62) and –6.5 points (SE, 0.47), respectively, in total motor AIMS score. These reductions were observed early and were sustained at week 145 for both the younger (percent change, –61.4%; SE, 4.10) and older group (–54.6%; SE, 3.01). Furthermore, 76% of younger participants and 62% of older participants achieved at least 50% improvement in total motor AIMS score from baseline.4

The new extended-release formulation is expected to be available in 3 tablet strengths: 6 mg, 12 mg, and 24 mg. All 3 can be administered with or without food. Teva noted that these provide an “updated regimen which may result in a decreased pill count for patients compared to the twice-daily formulation.

“Today’s approval marks an exciting milestone for patients with TD and HD chorea,” Sven Dethlefs, PhD, the executive vice president of North America Commercial at Teva, said in a statement.1 “Our commitment to patients suffering with these diseases is unwavering and we will continue our mission to address the needs of patients with neurodegenerative disorders.”

REFERENCES
1. Teva Announces FDA Approval of AUSTEDO® XR (deutetrabenazine) Extended-Release Tablets, a New Once-Daily Formulation of AUSTEDO® (deutetrabenazine) Tablets. News release. Teva. February 17, 2023. Accessed February 17, 2023. https://www.businesswire.com/news/home/20230217005357/en/Teva-Announces-FDA-Approval-of-AUSTEDO%C2%AE-XR-deutetrabenazine-Extended-Release-Tablets-a-New-Once-Daily-Formulation-of-AUSTEDO%C2%AE-deutetrabenazine-Tablets
2. Teva announces results from 3-year study assessing the safety and tolerability of Austedo (deutetrabenazine) tablets for the treatment of chorea associated with Huntington’s disease. News release. October 18, 2022. Accessed February 17, 2023. https://www.businesswire.com/news/home/20221018005197/en/Teva-Announces-Results-from-3-Year-Study-Assessing-the-Safety-and-Tolerability-of-AUSTEDO%C2%AE-deutetrabenazine-Tablets-for-the-Treatment-of-Chorea-Associated-with-Huntington%E2%80%99s-Disease
3. Frank S, Testa C, Edmondson MC, et al. The safety of deutetrabenazine for chorea in Huntington disease: an open-label extension study. CNS Drugs. 2022;36(11):1207-1216. doi:10.1007/s40263-022-00956-8
4. Sajatovic M, Finkbeiner S, Wilhelm A, et al. Deutetrabenazine in younger and older patients with tardive dyskinesia. Am J Geriatr Psychiatry. 2021;30(3):360-371. doi:10.1016/j.jagp.2021.08.003
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