Objective: To evaluate the long-term safety and activity of ecopipam (ECO) in the treatment of children and adolescents with Tourette syndrome (TS).

Background: D2 antagonists  treat Tourettes Syndrome in pediatric patients but carry safety limitation, notably metabolic adverse events (AEs), weight gain and the risk of extra-pyramidal symptoms (EPS). ECO is in development for the treatment of TS in pediatric patients.  In previous Phase 2 studies in adult and pediatric TS patients, ECO demonstrated clinical meaningful activity and was well-tolerated with no evidence of metabolic AEs or EPS.

Method: This was an open-label, single-arm extension study (OLE) in pediatric patients with TS who had previously completed a double-blind Phase 2 crossover proof of concept study (1) which enrolled patients aged > 7 and < 18, with both motor and vocal tics (minimum YGTSS-TTS of 20 at Baseline). . The primary endpoint of this OLE study was the change from Baseline to 12 months on the YGTSS-TTS. The key secondary endpoints were the change from Baseline to month 12 on the CGI-I and CGI-S. Safety was assessed by labs, AEs and the Children’s Depression Inventory (CDI).

Results: Patients (n=26 mean age of 13.4), were enrolled with a mean exposure of 366 days. ECO treatment resulted in significant improvement from Baseline to 12 months on the YGTSS-TTS (mean change -11.8, 95% CI -17.1 to -6.5; p=0.0003). Significant improvement was also seen at 3, 6 and 9 months. On the CGI-I, 80% of patients were much or very much improved from Baseline to 12 months (p<0.0001). The CGI-S also showed a significant improvement from Baseline to 12 months (p=0.001). The most frequently related AEs were suicidal ideation (3 of 26), decreased appetite, depressed mood, and irritability (seen in 2 of 26). Most adverse events were mild to moderate in severity and one patient experienced a serious adverse event of anxiety. Four subjects (15.4%) experienced non-severe AEs that led to discontinuation. There were no extra-pyramidal or metabolic adverse events. CDI was stable over time.

Conclusion: Ecopipam demonstrated sustained, one-year reduction in motor and phonic tics in pediatric TS patients, with no extra-pyramidal side effects or weight gain.

References: 1 Gilbert DL et al. Selective D1 receptor antagonism: clinical trial of a novel treatment for Tourette Syndrome. Movement Disorders 2018. 33: 1272-1280

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MDS Abstracts - https://www.mdsabstracts.org/abstract/long-term-safety-and-activity-of-ecopipam-eco-a-selective-d1-antagonist-during-treatment-of-pediatric-patients-with-tourette-syndrome/