Investigational Drug Lowers Tourette Relapse Risk in Kids

Children and adolescents with Tourette syndrome had a lower risk of relapses with investigational ecopipam, a phase III randomized withdrawal study showed.

Compared with placebo, ecopipam reduced relapse risk in 90 pediatric participants up to 24 weeks (HR 0.47, 95% CI 0.26-0.84, P=0.008), according to Donald Gilbert, MD, MS, of Cincinnati Children’s Hospital Medical Center in Ohio, and co-authors.

The effect appeared to be similar among 14 adult Tourette syndrome patients but was not significant (HR 0.51, 95% CI 0.11-2.30, P=0.37), the researchers reported in JAMA Neurology.

The study included a 12-week open-label period and a 12-week double-blind, randomized withdrawal period for participants who had clinically meaningful tic reductions.

During the open-label and double-blind phases, the most common side effects of ecopipam were somnolence (11.1%), anxiety (9.7%), headache (9.7%), insomnia (8.8%), tics (7.9%), and fatigue (6.5%). Suicidal ideation adverse events were reported in five participants (2.3%) during the open-label period and one participant (1.9%) in the placebo group during the randomized withdrawal period, the researchers said.

The drug did not have a clinically meaningful effect on weight, metabolic parameters, or psychiatric scale measures and did not appear to induce movement disorders, Gilbert and colleagues observed.

“Ecopipam maintained clinically meaningful Tourette symptom improvements and was well tolerated for up to 24 weeks,” they wrote. “Adverse events primarily affected the central nervous system.”

The trial follows a phase IIb study that showed pediatric Tourette syndrome patients had less tic severity over 12 weeks based on Yale Global Tic Severity Scale Total Tic Score (YGTSS-TTS) changes.

Tourette syndrome typically presents between ages 3 and 8 years with motor and phonic tics. Clinical courses vary, but peak tic severity commonly occurs between ages 8 and 12. Behavioral therapies are recommended as first line treatment.

Ecopipam is a first-in-class selective dopamine D1 receptor antagonist. Currently, initial pharmacotherapy for tics often involves an alpha-2 adrenergic agonist followed by topiramate as a subsequent treatment option, Gilbert and co-authors noted.

“Antipsychotics, currently the only approved medications for Tourette syndrome, are efficacious, but the risk of weight gain, adverse metabolic changes, and drug-induced movement disorders is a barrier to treatment,” they pointed out.

The phase III withdrawal study was conducted from 2023 to 2025 and included Tourette patients ages 6 years and older. During the open-label phase, ecopipam was titrated over 3 to 4 weeks to a target daily dose of 1.8 mg/kg. Responders who achieved at least 25% improvement on the YGTSS-TTS at weeks 8 and 12 were randomized to either continue ecopipam treatment or taper to placebo for the 12-week double-blind period.

The primary endpoint for pediatric participants — and an exploratory endpoint for adults — was time to relapse, defined as losing at least 50% of the YGTSS-TTS improvement gained during the open-label period.

The trial enrolled 216 participants in the open-label ecopipam period; most were pediatric and male. Of these, 43 pediatric and eight adult participants were randomized to receive ecopipam in the double-blind period; 47 pediatric and six adult participants were randomized to receive placebo. Pediatric patients had a mean age of 14.

Relapses occurred in 18 pediatric participants (41.9%) in the ecopipam group and 32 pediatric participants (68.1%) in the placebo group.

A secondary endpoint that combined pediatric and adult participants showed relapses occurred in 41.2% of the ecopipam group compared with 67.9% of the placebo group.

The study’s limitations included minimal racial and ethnic diversity. Safety assessments were restricted to 24 weeks, Gilbert and colleagues acknowledged. A small sample size resulted in low statistical power for the adult subgroup analysis, which was not pre-specified.

Drug developer Emalex Biosciences, recently acquired by Teva Pharmaceuticals, plans to submit a new drug application for ecopipam to the FDA later this year.