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A modified version of a currently used drug for Huntington disease offers a promising efficacy and safety profile, according to a phase III study
Tetrabenazine is the only licensed drug for the symptoms of chorea — involuntary muscle jerks — associated with the disease. However, it has to be taken up to three times a day and its metabolism can be unpredictable and can cause side effects such as sedation, depression and anxiety.
Deutetrabenazine, a modified form, was found to effectively reduce the symptoms of chorea compared with placebo when taken twice daily. The rate of adverse events, including depression and anxiety, was not significantly different from the placebo group. Physical function remained roughly static in the deutetrabenazine group, while it declined slightly in the placebo group.
“I think this is an interesting study,” says Roger Barker, consultant neurologist specialising in Huntington disease at Addenbrooke’s Hospital, Cambridge. “The new agent is designed to reduce side effects and frequency of administration. This study shows it offers some benefits in terms of adverse effects as well as helping with chorea and [patients’] general overall health.”
Deutetrabenazine will be added to the available agents for chorea, including tetrabenazine and olanzapine, which is commonly used off-licence, he says.
“However, the real need in this disease is to find [an] effective disease modifying agent and/or therapies that help the non-motor aspects of the condition — especially the apathy and cognitive deficits that are so prevalent and disabling in Huntington disease,” adds Barker.
Researchers randomised 90 patients with Huntington disease to either deutetrabenazine or placebo for 12 weeks. In the deutetrabenazine group, symptoms of chorea improved from 12.1 to 7.7, compared with an improvement from 13.2 to 11.3 in the placebo group. The average difference between groups was –2.5 units (95% confidence interval –3.7 to –1.3) (P < 0.001). According to the Patient Global Impression of Change, treatment was deemed to be successful in 51% of patients in the deutetrabenazine group compared with 20% of patients in the placebo group, while according to the Clinical Global Impression of Change, treatment was successful in 42% and 13% of patients, respectively.
Deutetrabenazine has a similar chemical structure to tetrabenazine. However, in certain parts of its molecular structure, normal hydrogen has been replaced with a form of hydrogen called deuterium. It has a heavier mass and forms a stronger bond to carbon atoms, slowing down its metabolism in the body.
The authors of the study say this is the first time a deuterated drug has reached phase III clinical trials. They are positive about the results, saying that the improvement in chorea seen with deutetrabenazine is similar to that measured in the phase III study of tetrabenazine. But they caution that further research is needed to establish the clinical significance of the change.
The drug, which is manufactured by Teva, is currently under consideration for approval by the US Food and Drug Administration.