Real-world study backs approved chorea treatment’s use in Huntington’s
Switching from older drug after treatment gap shows best results
Written by |
A real-world study shows that the approved chorea treatment Austedo (deutetrabenazine) reduces involuntary movements in adults with Huntington’s disease and is generally well tolerated in clinical settings.
According to the researchers, most patients experienced a decrease in the severity of their chorea — involuntary muscle movements that can be a symptom of Huntington’s — after reaching a stable treatment dose. Further, greater effects were seen among individuals who switched to Austedo from the older approved chorea drug Xenazine (tetrabenazine) after a treatment gap.
Both Xenazine, sold in the U.S. by Lundbeck Pharmaceuticals, and Austedo, developed by Teva Pharmaceuticals, are widely used for treating chorea in people with Huntington’s.
“Altogether, these results support the tolerability and chorea symptom [easing] due to [Austedo] for the treatment of patients with chorea associated with [Huntington’s disease], regardless of prior treatment,” the researchers wrote.
The study, “Real-world treatment patterns and outcomes of deutetrabenazine in patients with chorea associated with Huntington disease: A retrospective chart review study,” was published in the Journal of Huntington’s Disease. The work was funded by Teva Branded Pharmaceutical Products R&D, and five of the study’s 11 authors were employed by Teva companies. Another four authors work for a consulting firm paid by Teva Pharmaceuticals. The research was led by two scientists at the University of Alabama at Birmingham.
Huntington’s is caused by mutations in the HTT gene that result in the production of an abnormally long version of the huntingtin protein — essential for brain development and nerve cell survival — that is prone to forming toxic clumps in nerve cells. This leads to the loss of those cells and consequent disease symptoms, such as movement issues, including chorea.
Austedo has been approved for nearly a decade in the U.S. for treating chorea in adults with Huntington’s. It works by suppressing the activity of vesicular monoamine transporter 2 (VMAT2), a protein responsible for the transport of dopamine, a signaling molecule nerve cells use to communicate.
Clinical trials have shown that, compared with a placebo, Austedo can reduce chorea in Huntington’s patients. However, less is known about how it performs in real-world practice.
Researchers compared Austedo and Xenazine in real life
To learn more, the research team conducted a retrospective analysis of 80 people with Huntington’s-associated chorea. The patients, slightly more than half of whom were women, had a mean age of 52.1. Each had started Austedo as part of routine clinical practice at the University of Alabama at Birmingham between 2017 and 2021. All were followed up for 34.2 months, or nearly three years.
Slightly more than half (56%) had received treatment for chorea before the study’s starting point. Among those patients, 48% had taken Xenazine, another VMAT2 inhibitor, while 8% — six patients, who were excluded from the later calculations — had been on Austedo as part of a clinical trial. The researchers noted that discontinuation of Xenazine was usually due to low tolerability and/or a lack of effectiveness.
In the analysis, patients were grouped according to their previous treatment: 37 had not received either Xenazine or Austedo; 13 switched from Xenazine to Austedo after a treatment gap; and 24 switched directly from Xenazine to Austedo.
Patients started on a mean dose of Austedo of 15.3 mg/day, with 91% reaching a mean stable dose of 39.2 mg/day after about 16 months, or about 1.4 years. Almost all individuals (85%) who reached a stable dose of Austedo were also taking at least one other medication, more commonly antipsychotics (38%), the data showed.
A total of 50 patients had measures of total maximal chorea (TMC) score, a standardized tool to assess the severity and frequency of the symptom, both before starting Austedo and after reaching the last stable dose. Most of these individuals (84%) experienced a reduction in TMC score, which indicates less severe chorea. For 14%, the score increased, while in 2% it remained stable.
Overall, participants showed a 4.2-point reduction in TMC (from 12.0 to 7.8), with larger reductions (by 7.8 points) observed in participants who previously received Xenazine and switched to Austedo after a treatment gap.
According to researchers, this decrease is consistent with the decrease observed in the Phase 3 trial that supported Austedo’s approval for Huntington’s-associated chorea.
This real-world study shows that [Austedo] is associated with [reductions] in chorea associated with [Huntington’s] and is generally well tolerated, including in patients with prior [Xenazine] exposure.
Austedo was generally well tolerated, with one-third of the participants experiencing at least one adverse event. The most common adverse events were sedation, sleepiness, and fatigue, reported in 18% of participants. Five patients (6%) stopped Austedo due to adverse events or tolerability concerns.
According to the researchers, “this real-world study shows that [Austedo] is associated with improvements in chorea associated with [Huntington’s] and is generally well tolerated, including in patients with prior [Xenazine] exposure.”
Among the seven participants who discontinued Xenazine due to lack of effectiveness, five experienced a reduction in chorea, with a mean TMC score reduction of 3.7 points, the data showed.
The researchers stressed that the study findings should be interpreted cautiously due to the low number of patients, as well as its restrospective, single-center design.
Still, the team noted that these results “highlight the real-world effectiveness of [Austedo] among patients in whom [Xenazine] was previously ineffective; however, further studies are warranted to confirm this finding.”
Leave a comment
Fill in the required fields to post. Your email address will not be published.