Novel drug promising for paediatric Tourette syndrome

The experimental drug ecopipam helps minimize motor and phonic tics in children and adolescents with Tourette syndrome, in addition to being safe and well tolerated, according to the results of a phase 2b trial presented at the 2022 American Academy of Neurology’s Annual Meeting (AAN 2022).

After 3 months of treatment, the tic symptoms were fewer and less severe among children on ecopipam (n=74) than those on placebo (n=75), said one of the investigators, Dr Donald Gilbert of the Cincinnati Children’s Hospital Medical Center in Ohio, US, and a Fellow of the AAN.

The Yale Global Tic Severity Score - Total Tic Score (YGTSS-TTS; 0–50) decreased by 30 percent (from 35 at baseline to 24 at week 12) in the active treatment arm as opposed to 19 percent (from 35 to 28) in the control arm (least square [LS] mean difference, –3.44, 95 percent confidence interval [CI], –6.09 to –0.79; p=0.011). [Mahableshwarkar A, et al, AAN 2022]

The findings were consistent and favoured ecopipam in the subgroups of children aged 6–11 years (LS mean difference, –4.95, 95 percent CI, –9.99 to 0.10; p=0.054) and 12–17 years (LS mean difference, –3.37, 95 percent CI, –6.51 to –0.24; p=0.035).

In a test that assessed the overall effectiveness of the drug, the ecopipam arm likewise showed a greater improvement in the Clinical Global Impression of Tourette Syndrome Severity (CGI-TS-S; 1–100) at week 12. The average CGI-TS-S score decreased by 32 percent (from 68 to 46) as compared with a decrease of 20 percent (from 66 to 54) in the control arm (p=0.001).

Gilbert noted that there were 26 (34 percent) patients on ecopipam and 16 (21 percent) on placebo who developed treatment-related adverse events (AEs), such as headache (9.2 percent), fatigue (6.6 percent), somnolence (6.6 percent), and restlessness (5.3 percent). None of the patients experienced metabolic or movement-related AEs or treatment-related serious AEs.

“Our results are exciting, because they suggest ecopipam shows promise as a treatment for reducing the number, frequency, and severity of the tics young people experience with Tourette syndrome,” Gilbert said in a statement. “That’s especially true because many people with the disease who are taking the medications currently available still have debilitating symptoms or experience weight gain or other side effects.”

Ecopipam is an investigational first-in-class selective dopamine-1 (D1) receptor antagonist developed for the treatment of Tourette syndrome in paediatric patients and childhood-onset fluency disorder or stuttering in adults. 

The drug works by selectively blocking the activity of the neurotransmitter dopamine at the D1 receptor. D1-receptor super-sensitivity has been postulated to be a mechanism for the repetitive and compulsive behaviours associated with Tourette syndrome. [tinyurl.com/y359zu6n]

“Dopamine receptors are found in the central nervous system. When they receive dopamine, they create signals for various mental and physical functions like movement. Different receptors help control different functions,” Gilbert explained.

“While ecopipam is still in the testing phase, it is the first drug to target the D1 receptor instead of the D2 receptor, which is the one targeted by medications currently on the market. Our results demonstrate that ecopipam deserves more study as a viable treatment option for Tourette syndrome in young people in the future,” he stated.

Gilbert, however, acknowledged that the 3-month duration of the current trial was a limitation, pointing out that while the duration is standard for the trials of the same type, it will be necessary to establish whether or not symptom improvements persist longer.