Ecopipam phase 3 data demonstrates reduced Tourette relapse risk in youth

A phase 3 trial of ecopipam (Emalex Biosciences), an investigational dopamine D1 receptor antagonist, suggests continued treatment may reduce relapse risk among children and adolescents with Tourette syndrome who initially respond to therapy, according to an announcement from Cincinnati Children’s Hospital Medical Center and Emalex Biosciences.¹

“I hope this will be the first drug approved specifically for Tourette syndrome in the US,” said Donald Gilbert, MD, MS, principal investigator of the 77-site trial and a pediatric movement disorders specialist at Cincinnati Children’s. “There are 3 other drugs that are approved by the US FDA, but they are all antipsychotics that were initially approved for treating schizophrenia. This drug works in the brain a totally different way.”¹

The findings, described in a recent JAMA Neurology publication cited in the announcement, are expected to support a planned FDA submission by Emalex. Ecopipam is not currently FDA approved, but it has received Orphan Drug and Fast Track designations for pediatric Tourette syndrome.¹

Tourette syndrome is a chronic neurodevelopmental disorder characterized by motor and vocal tics, typically emerging in childhood. The disorder affects an estimated 1% of school-aged children and is more common among boys.¹ Current management includes education, behavioral therapy such as comprehensive behavioral intervention for tics, and pharmacotherapy when tic severity causes functional impairment, pain, psychosocial distress, or interference with school or activities.²

The phase 3 study used a randomized-withdrawal design. All 216 participants, including 167 children and adolescents, first received open-label ecopipam for 12 weeks. Investigators then randomized 104 participants, including 90 pediatric patients, to continue ecopipam or switch to placebo for another 12 weeks to assess maintenance of tic improvement.¹

According to the announcement, participants who continued ecopipam had a 50% lower risk of relapse compared with those who received placebo. Adverse events were described as generally mild to moderate and consistent with earlier studies. The release did not provide absolute relapse rates, detailed adverse-event frequencies, or subgroup results by age, tic severity, or comorbid psychiatric diagnoses.¹

Ecopipam’s proposed role differs mechanistically from currently approved tic medications. Haloperidol, pimozide, and aripiprazole are FDA-approved options for tics associated with Tourette syndrome and act primarily through dopamine D2 receptor pathways.¹,³ These agents can be effective, but their use in children is limited by adverse effects that may include sedation, weight gain, extrapyramidal symptoms, Parkinsonism, akathisia, and, rarely, tardive dyskinesia.²,³

By contrast, ecopipam targets the dopamine D1 receptor. The theoretical appeal is tic reduction without some D2 receptor–mediated adverse effects, although the comparative safety profile will require full review of the phase 3 data and, if submitted, FDA assessment. Earlier phase 2 data published in Pediatrics reported that ecopipam was superior to placebo for tic reduction over 12 weeks, according to the current announcement.¹,⁴

“Overall, the patients taking ecopipam got significant help with their tics, didn’t gain weight, and didn’t develop other movement disorders,” Gilbert said. “That’s an exciting combination that could make pediatricians more willing to prescribe treatment and families more willing to consider medication.”¹

For clinicians, the phase 3 results are most relevant to children and adolescents who respond to initial ecopipam treatment and are candidates for ongoing pharmacologic therapy. The randomized-withdrawal design supports maintenance of response, but it does not answer all questions about first-line comparative efficacy, long-term safety, durability beyond 24 weeks, or how ecopipam would perform against behavioral therapy, alpha-2 agonists, or antipsychotics in routine practice.

The study was funded by Emalex Biosciences and included authors affiliated with Emalex, Bittman Biostat, Paragon Biosciences, Cincinnati Children’s, and Boston Children’s Hospital.¹ Participants have been allowed to continue treatment after the trial, and an expanded access program is available for eligible patients who lack access to approved therapies or have experienced treatment failure, tolerability concerns, or safety issues with existing options.¹

Next steps include regulatory submission and review. Until FDA action occurs, ecopipam remains investigational, and clinicians should interpret the findings in the context of the published trial details, existing guideline recommendations, and the individual burden of tics and comorbidities for each patient.

References

1. Cincinnati Children’s Hospital Medical Center. New med to manage Tourette syndrome shows promise in phase III clinical trial. PRNewswire. Published May 22, 2026. Accessed May 26, 2026. https://www.prnewswire.com/news-releases/new-med-to-manage-tourette-syndrome-shows-promise-in-phase-iii-clinical-trial-302782064.html

2. Pringsheim T, Okun MS, Müller-Vahl K, et al. Practice guideline recommendations summary: treatment of tics in people with Tourette syndrome and chronic tic disorders. Neurology. 2019;92(19):896-906. doi:10.1212/WNL.0000000000007466

3. US Food and Drug Administration. Abilify (aripiprazole) Prescribing Information. US Food and Drug Administration. Updated January 2025. Accessed May 26, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/021436s046s050lbl.pdf

4. Gilbert DL, Dubow JS, Cunniff TM, Wanaski SP, Atkinson SD, Mahableshwarkar AR. Ecopipam for Tourette Syndrome: A Randomized Trial. Pediatrics. 2023;151(2):e2022059574. doi:10.1542/peds.2022-059574