12-Month Extension Data Highlights Ecopipam as an Effective Option for Tourette Syndrome

Donald L. Gilbert, MD, MS

Data from an open-label extension (OLE) of a phase 2b study recently published in Movement Disorders showed that treatment with investigational ecopipam (Emalex Biosciences) was safe and effective in patients with Tourette syndrome (TS) over a 12-month period. The findings, which showed reduced TS symptom severity and improved quality of life (QOL) in children and adolescent patients, further support the development of the dopamine-1 receptor antagonist as a treatment for TS.¹

The study featured 121 patients (6-11 y: 32.2%; 12-18 y: 67.8%) on at least 1 dose of ecopipam at 1.8 mg/kg/day who previously completed a phase 2b randomized, placebo-controlled, 12-week trial. Of these, 80 (66.1%) completed the study. Throughout the 12-month OLE, ecopipam continued to show a safe and tolerable profile, with the most common adverse events being nasopharyngitis (14.0%) and anxiety (9.0%), most of which were mild or moderate in nature.

Led by Donald L. Gilbert, MD, MS, a pediatric neurologist at Cincinnati Children’s Hospital Medical Center, additional safety findings showed that AEs of special interest were found in nearly one-fifth (19.8%) of the cohort. Dose reductions caused by AEs were observed in 6 patients (100 mg to 75 mg [n = 3]; not determined [n = 2];75 mg to 12.5 mg [n = 1]), all of whom received placebo during the phase 2b trial. Notably, suicidal ideation was reported in 3 patients (2.5%); however, no suicidal behavior was identified during the study. Among these patients, dose changes were not deemed necessary by the study investigators.

Over the 12-month extension, there were no significant changes in glycated hemoglobin (mean change, 0.03 [SD, 0.31]; P = .60), total cholesterol (0.2 [SD, 0.7] mmol/L; P = 0.14), triglycerides (0.09[SD, 0.64] mmol/L; P = 0.46), diastolic blood pressure (0.9 [SD, 10.0]mm Hg; P = 0.44), or systolic blood pressure (0.3 [SD, 11.5] mmHg; P = 0.85). Notably, patients treated with ecopipam showed no significant change in body mass index z-score (mean change, 0.05 [SD, 0.43]; P = .35) over that time.

Patients on the investigational agent also showed no notable changes in several other safety assessments, including Abnormal Involuntary Movement Scale, which looks at movement disorders involving the extremities, face, mouth and trunk, as well as Barnes Akathisia Rating Scale, which focuses on drug-induced akathisia. In addition, there were no changes in Children’s Depression Rating Scale-Revised, and Pediatric Anxiety Rating Scale over the 12-month time period.

In addition to demonstrating a well-tolerated profile, treatment with ecopipam led to significant improvements in YGTSS-TT across all time points of the OLE (P <.0001), with treated patients demonstrating a mean 40.3% reduction during the 12-month period. Of note, the significant improvements in YGTSS-TT were found in both patients who started on ecopipam and those who switched from placebo. In addition, significant mean improvements from baseline in the C&A-GTS-QOL total score were observed through month 12 (P < 0.001 at all timepoints), with a mean change of 8.0 (SD, 16.2) at month 12.

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The study had several limitations, including the absence of a control arm, exclusion of adults with Tourette syndrome (TS), and limited racial and ethnic diversity. Additionally, only one-third of participants were aged 6 to 11, possibly due to lower motivation in this age group, less exposure to prior treatments, and a preference among caregivers and providers to try first-line therapies before enrolling in investigational studies.

Ecopipam most recently showed promise in a phase 3 study dubbed D1AMONDs (NCT05615220), with results that may lead to a potential new drug application submission for ecopipam. In the study, 41.9% of pediatric patients with TS randomized to ecopipam experienced a relapse compared with 68.1% of those on placebo (hazard ratio, 0.5 [0.3-0.8]; P = .0084). For the secondary efficacy end point, which assessed time to relapse in both pediatric and adult participants after randomization, findings showed that 41.2% of patients in the ecopipam group relapsed, compared with 67.9% in the placebo group (hazard ratio, 0.5 [0.3-0.8]; P = .0050).

Frederick Munschauer, MD

At the time, Frederick Munschauer, MD, chief medical officer at Emalex Biosciences, told NeurologyLive® that "We now have two successful adequate and well-controlled clinical studies that we believe will support marketing authorization applications. Our first registrational trial established the efficacy of ecopipam in Tourette syndrome with a favorable safety profile. This second registrational trial supports that efficacy and confirms the durability of the treatment effect over a longer trial period. We were also heartened to see that the tolerability and safety profile was similar between the two registrational trials."

In the phase 3 trial, 167 pediatric and 49 adult patients with TS were enrolled across sites in the US, Canada, and the European Union. Following a 12-week open-label period with ecopipam, participants who experienced significant improvement in motor and vocal tics were randomized to either continue ecopipam or switch to placebo for a 12-week double-blind withdrawal phase. Ecopipam was generally well tolerated, with the most commonly reported adverse events being somnolence (10.2%), insomnia (7.4%), anxiety (6.0%), fatigue (5.6%), and headache (5.1%).

REFERENCES
1. Gilbert DL, Kim DJB, Miller MM, et al. Safety and Effect of 12-Month EcopipamTreatment in Pediatric Patients with Tourette Syndrome. Movement Disorders. Published online May 12, 2025. doi:10.1002/mdc3.70091
2. Emalex Biosciences’ Lead Candidate Meets Primary and Secondary Endpoints in Phase 3 Tourette Syndrome Study. News Release. Emalex Biosciences. Published February 25, 2025. Accessed June 13, 2025. https://emalexbiosciences.com/news/emalex-biosciences-lead-candidate-meets-primary-and-secondary-endpoints-in-phase-3-tourette-syndrome-study/