Long-term Austedo Safely Leads to Reductions in Chorea: 3-year Data
Switching from Xenazine to Austedo also found to be safe and effective
Long-term treatment with Austedo (deutetrabenazine) safely led to sustained reductions in chorea for people with Huntington’s disease, including those who had switched from treatment with Xenazine (tetrabenazine).
That’s according to about three years of follow-up data in the Phase 3 ARC-HD trial (NCT01897896), a study jointly conducted by Austedo’s developer, Teva Pharmaceuticals, and the Huntington Study Group.
Not only do the data support Austedo’s long-term tolerability and effectiveness, but they highlight that patients switching from Xenazine can do so safely.
“These data provide important insight into the long-term use of [Austedo] for the treatment of chorea associated with Huntington’s disease, which can have a significant functional impact on people’s lives,” Samuel Frank, MD, the study’s first author, said in a Teva press release. Frank is an associate professor of neurology and director of the Huntington’s Disease Society of America Center of Excellence at Beth Israel Deaconess Medical Center, in Boston.
“Results of this study add to the safety and tolerability profile and support [Austedo] as a treatment choice for this progressive condition,” Frank added. “We are deeply grateful to the researchers, patients and their families who played an integral role in this study.”
The findings were detailed in the study “The Safety of Deutetrabenazine for Chorea in Huntington Disease: An Open‑Label Extension Study,” published in the journal CNS Drugs.
Chorea, marked by involuntary, abrupt, and irregular movements, “is one of the most striking physical manifestations of Huntington’s Disease that occurs in approximately 90% of HD [Huntington’s disease] patients,” said Eran Harary, MD, Teva’s senior vice president and global head of specialty R&D.
Oral Austedo approved in the US in 2017 for Huntington’s-related chorea
Austedo, an oral treatment, has been approved in the U.S. since 2017 for chorea in Huntington’s patients. It works by suppressing VMAT2, a molecule involved in the release of dopamine — a brain signaling molecule whose abnormally high levels have been implicated in Huntington’s chorea — between nerve cells.
While its mechanism of action is similar to Lundbeck Pharmaceuticals’ Xenazine, a first-generation, oral VMAT2-suppressor approved for Huntington’s chorea, it is broken down more slowly in the body, thereby prolonging its effects.
Austedo’s approval was backed by data from the Phase 3 First-HD trial (NCT01795859), which enrolled 90 adults with Huntington’s. Data showed that Austedo, taken three times a day for three months, led to significant reductions in Huntington’s-associated chorea compared with a placebo.
After completing First-HD, and undergoing a one-week washout period, 82 participants entered an open-label Phase 3 study called ARC-HD, in which all received Austedo twice a day for up to three years.
In addition to these so-called “rollover” patients, ARC-HD also recruited 37 Huntington’s patients who had been on a stable dose of Xenazine for at least two months. These patients, dubbed the “switch” group, were transitioned overnight to Austedo.
Results of this study add to the safety and tolerability profile and support [Austedo] as a treatment choice for this progressive condition
ARC-HD trial enrolls 119 patients
Overall, 119 ARC-HD participants were followed for a mean of 116 weeks (little over two years) in the rollover group and 124 weeks (nearly 2.5 years) in the switch group.
Austedo doses were increased for the first eight weeks to reach an optimal dose, ultimately reaching a daily maintenance dose of 6–72 mg. Across both groups, the mean daily dose of Austedo was 45.7 mg at the final study visit.
Throughout the three-year ARC-HD study, compliance rates for taking the medication remained over 90%, with an overall median compliance of 97% in the rollover group and 93% in the switch group.
Chorea was assessed with the Unified Huntington’s Disease Rating Scale (UHDRS) total maximal chorea scores, with higher scores reflecting a greater degree of the movement disorder.
Results showed that chorea scores were significantly decreased in both groups after eight weeks of treatment in the ARC-HD trial. But this reduction was more pronounced in the rollover group, whose scores dropped by 4.5 points compared with 2.1 points in the switch group.
No new safety concerns identified with Austedo
As previously reported, this meant that Austedo effectively lessens chorea and to a greater extent than Xenazine.
UHDRS total motor scores were also decreased in both groups after eight weeks, reflecting improvements in overall motor function.
Notably, in both groups, reductions in chorea were generally maintained for the duration of follow-up, while motor scores increased again during follow-up.
Austedo had a safety profile comparable to that observed in the First-HD study, with no new safety concerns identified.
Around 70% of patients in either group experienced an adverse event that could have been related to Austedo treatment. Common adverse events included fall (38%–43%), depression (22%–32%), anxiety (27%–35%), insomnia (16%–23%), and sleepiness (20%–30%).
These findings highlight that in Huntington’s patients, “including those who previously benefited from [Xenazine], chorea control can be maintained and improved through long-term use of twice-daily [Austedo], with favorable safety and tolerability,” the researchers wrote.
Harary added: “As a disease that can have significant functional impact on patients’ and caregivers’ lives, we’re proud to share these new data to provide valuable insights for this community of patients and for those who provide care to them each day.”