Teva Submits NDA for Ecopipam, Potential First New Tourette Syndrome Treatment in Over a Decade

Teva Pharmaceutical announced the submission of a New Drug Application (NDA) to the FDA for ecopipam, a first-in-class selective dopamine D1 receptor (D1R) antagonist for pediatric Tourette syndrome (TS).¹ If approved, ecopipam would be the first new FDA-approved treatment for TS in more than a decade and the first non-antipsychotic pharmacotherapy ever approved for the condition, addressing a mechanism distinct from the D2 receptor blockade underlying all currently approved options.

“The NDA submission for ecopipam is a significant milestone for a potential first-in-class treatment option in pediatric Tourette syndrome,” Eric Hughes, MD, PhD, Executive Vice President, Global R&D and Chief Medical Officer of Teva, said in a statement.¹ “This reflects the momentum in our innovative pipeline through our recent acquisition of this important asset, and advances our Pivot to Growth strategy and commitment to bringing differentiated medicines for patients.”

The submission is supported by phase 3 data published in JAMA Neurology earlier this year.² The double-blind, placebo-controlled, randomized withdrawal trial (NCT05615220) enrolled 216 participants across 77 sites in 12 countries, including the US, Canada, and multiple European countries, between January 2023 and February 2025. Eligible participants were 6 years or older with a TS diagnosis and a Yale Global Tic Severity Scale Total Tic Score (YGTSS-TTS) of 20 or greater at baseline.

Trial Design

The trial used a 12-week open-label period followed by a 12-week double-blind, randomized withdrawal period. During the open-label period, all 216 participants received ecopipam titrated to a target dose of 1.8 mg/kg per day. Participants achieving at least 25% improvement in YGTSS-TTS at both weeks 8 and 12 were randomized 1:1 to continue ecopipam or taper to placebo for the 12-week double-blind period.

Of the 216 enrolled, 167 (77.3%) were pediatric participants. A total of 104 participants were randomized to the double-blind period (51 ecopipam, 53 placebo), comprising 90 pediatric participants (the primary analysis population) and 14 adults (exploratory). The primary endpoint was time to relapse in the pediatric population, with relapse defined as 50% or greater loss of YGTSS-TTS improvement, initiation of additional TS medications, or hospitalization for worsening symptoms.

Efficacy Results

Ecopipam met its primary endpoint. In the pediatric population, the drug significantly reduced relapse risk compared with placebo (hazard ratio [HR], 0.47; 95% CI, 0.26-0.84; P = .008). Relapse occurred in 68.1% of placebo-treated pediatric participants versus 41.9% of those who continued ecopipam. Median time to relapse was 4.0 weeks for placebo, while the median was not reached for ecopipam because more than half of participants maintained improvement through week 24.

The secondary endpoint, time to relapse in the overall population (ages 6 and older), also showed a significant treatment effect (HR, 0.47; 95% CI, 0.28-0.81; P = .005), with relapse in 67.9% of placebo-treated versus 41.2% of ecopipam-treated participants. In the small exploratory adult-only subgroup (n = 14), the effect was directionally consistent (HR, 0.51; 95% CI, 0.11-2.30) but did not reach statistical significance (P = .37), reflecting limited statistical power in this subgroup.

Exploratory endpoints supported the primary findings. The least-squares mean difference in YGTSS-TTS change from randomization to end of treatment was −5.1 points favoring ecopipam (95% CI, −8.8 to −1.4; P = .009), with significant differences also favoring ecopipam on motor and phonic subscales and both Clinical Global Impression of Tourette Syndrome scales (P ≤ .03 for all). During the open-label period, mean YGTSS-TTS improvement from baseline was 47.5% in pediatric participants and 38.9% in adults among those completing week 12.

Safety

Ecopipam was generally well tolerated. Across the full 216-participant open-label cohort, 68.1% reported at least one adverse event, most mild or moderate. The most common were somnolence (11.1%), anxiety (9.7%), headache (9.7%), insomnia (8.8%), tic (7.9%), and fatigue (6.5%).² Discontinuation due to AEs occurred in 15.7% of participants during the open-label period and in none of the ecopipam-treated participants during the double-blind period.

Notably, the trial found no clinically meaningful changes in body mass index, glycated hemoglobin, lipid levels, ECG measurements, or prolactin, and no drug-induced movement disorders were observed, a profile that contrasts with the metabolic and motor side effects associated with currently available antipsychotic therapies for TS. Serious adverse events occurred in 4 participants (2 possibly or probably treatment-related), and suicidal ideation rates were low and did not differ meaningfully between arms during the randomized withdrawal period.

Clinical and Regulatory Context

Only three medications currently carry FDA approval for TS: haloperidol, approved in the 1960s; pimozide, approved in 1984; and aripiprazole, approved in 2014, the most recent addition.⁴ All three work through dopamine D2 receptor blockade and carry risks of weight gain, metabolic disturbance, and drug-induced movement disorders, limitations that have driven high rates of treatment discontinuation. Behavioral therapy remains first-line, with alpha-2 adrenergic agonists such as clonidine and guanfacine and topiramate also used off-label before antipsychotics are considered.³

All currently approved TS medications work through dopamine D2 receptor blockade and carry risks of weight gain, metabolic disturbance, and drug-induced movement disorders. Ecopipam's mechanism, selective D1 antagonism, is based on the hypothesis that D1 receptor hypersensitivity contributes to the repetitive, compulsive behaviors characteristic of TS. The FDA has granted ecopipam both Orphan Drug and Fast Track designations for pediatric TS.

Limitations

The phase 3 trial enrolled a population with minimal racial and ethnic diversity (90.7% White), and the adult subgroup was small and not statistically powered. The randomized withdrawal design assessed only maintenance of efficacy among open-label responders, rather than treatment-naive efficacy, which may limit generalizability. Safety follow-up was limited to 24 weeks, and the NDA submission does not guarantee FDA approval.

REFERENCES
1. Teva submits NDA for ecopipam, a first-in-class investigational therapy for pediatric Tourette syndrome. News release. Teva Pharmaceutical Industries Ltd. June 18, 2026. Accessed June 18, 2026. https://ir.tevapharm.com/news-and-events/press-releases/press-release-details/2026/Teva-Submits-NDA-for-Ecopipam-a-First-in-Class-Investigational-Therapy-for-Pediatric-Tourette-Syndrome/default.aspx
2. Gilbert DL, Atkinson SD, Kim DJB, et al. Efficacy and safety of ecopipam for Tourette syndrome: a phase 3 randomized clinical trial. JAMA Neurol. Published online May 26, 2026. doi:10.1001/jamaneurol.2026.1431. https://jamanetwork.com/journals/jamaneurology/fullarticle/2849573
3. 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. https://doi.org/10.1212/WNL.0000000000007466
4. Highlights of prescribing information: Abilify (aripiprazole). US Food and Drug Administration. Accessed June 18, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021436s038,021713s030,021729s022,021866s023lbl.pdf