Continued use of a drug called ecopipam can cut the risk of relapse in half for children battling tics caused by Tourette syndrome (TS).
That’s the key finding published in JAMA Neurology describing the results of a recently completed phase III clinical trial of the first drug designed to help children with this condition. Next, the drug maker Emalex Biosciences plans to seek approval from the U.S. Food and Drug Administration to take the new medicine to market.
The principal investigator for the 77-site clinical trial was Donald Gilbert, a movement disorders expert with the Division of Neurology at Cincinnati Children’s.
“I hope this will be the first drug approved specifically for Tourette syndrome in the US,” Gilbert said.
“There are three 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.”
TS is a chronic neurodevelopmental disorder, most often appearing before age 10, and occurring more commonly among boys. The condition is known for uncontrolled motor and vocal tics, such as blinking, shrugging, or grunting. TS affects about 1% of school-aged children.
For years, clinicians have prescribed various treatments to help control tics, including behavioural therapies, medications, and, in severe cases, deep brain stimulation. Currently, the only FDA-approved drugs to manage tics are haloperidol (Haldol), pimozide (Orap), and aripiprazole (Abilify). All of these medications disrupt the function of dopamine via “D2” receptors in the brain that can trigger excessive neuronal activity, which in turn can lead to tic movements and sounds.
The downside of these drugs have been side effects including weight gain, shakiness, stiffness, and Parkinson-like symptoms such as drooling, falling, or walking problems. In rare cases, longer term medication use results in tardive dyskinesia (TD), another movement disorder noted for causing people to repeatedly protrude their tongues.
The investigational compound ecopipam acts against the dopamine D1 receptor instead of the D2 receptor. This difference, experts say, results in a treatment that significantly reduces the risk of tics while also causing fewer side effects. Gilbert has been involved with studying this drug since its early days.
A major step forward occurred in 2023, when results of a phase II study were published in Pediatrics. This showed that ecopipam was superior to placebo in reducing tics over 12 weeks.
To assess benefit for up to 24 weeks, the phase III study started with 12 weeks of open label treatment for 216 participants (including 167 children and teens). Then, to see whether tic improvement was maintained, 104 participants (90 paediatric) were randomised to receive either ecopipam or placebo for 12 additional weeks.
Those who continued ecopipam showed a 50% risk reduction for relapse compared with those receiving the placebo. Meanwhile, adverse events were generally mild to moderate and consistent with previous, smaller-scale trials.
“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 paediatricians more willing to prescribe treatment and families more willing to consider medication.”
While the clinical trial is over, participants have been allowed to continue taking the drug.
Some patients not involved in the study also have been able to start receiving ecopipam through an Expanded Access Program. This allows physicians to request the medication for eligible patients who either lack access to other approved medications or have tried them only to experience treatment failure, tolerability or safety issues.
Ecopipam has not been approved by the U.S. Food and Drug Administration but has received Orphan Drug and Fast Track designation for the treatment of paediatric patients with Tourette syndrome.