A clinical drug trial led by a Cincinnati Children’s researcher shows positive results in reducing tics for children and teens living with Tourette syndrome. Ecopipam (EBS-101) is an investigational, first-in-class dopamine-1 (D1) receptor antagonist developed by Emalex Biosciences, LLC. The Phase 2b clinical study (D1AMOND study) led by Donald Gilbert, MD, MS, a pediatric movement disorders and Tourette syndrome specialist at Cincinnati Children’s, showed a significant reduction in vocal and motor tics experienced by youth with Tourette syndrome who received ecopipam as part of the clinical trial. On average:

• Participants taking ecopipam improved their motor and vocal tic severity score from 35 to 24, a decrease of 30%, compared to a decrease of 19% on placebo.  

• 74% of participants taking ecopipam experienced a >25% reduction in tic severity, compared to 43% on placebo.  

“After decades of research in pediatric neurology and psychiatry, it is extremely gratifying to achieve positive and meaningful study results for a patient group that has such a high unmet medical need,” Gilbert says. “We are one step closer to a potentially life-changing therapy for a patient group who inspires and fuels our efforts.” 

Study Suggests Ecopipam Significantly Reduces Tics

The D1AMOND study was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study evaluating the efficacy and safety of ecopipam. The trial included 153 children ages 6 to 18 who participated in a 12-week treatment course at 63 sites across the US, Canada , and Europe.  

Participants were randomly divided into two groups:  

• 74 received ecopipam tablets at a dose of 2 mg/kg/day. 

• 75 received placebo tablets. 

Study medication was titrated to the target dose over four weeks and then maintained for an eight-week treatment period.  Researchers rated the severity of participants’ tics using two common tic rating scales at the beginning of the study and again three months later: The first test Yale Global Tic Severity Score-Total Tic Score (YGTSS-TTS) measures the motor and vocal tics. The second test Clinical Global Impression of Tourette Syndrome Severity (CGI-TS-S) looks at overall tic symptoms and severity of tic-related impairment. After three months, researchers found that the group taking ecopipam had statistically significant and clinically meaningful results. Those on ecopipam had fewer and less severe tics and were doing better overall on both test scores. Results were presented at the American Academy of Neurology’s 74th annual meeting in April 2022. 

“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 says. “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.” 

Future Investigation Needed to Determine Long-term Results

Ecopipam is the first drug for Tourette syndrome to target the D1 receptor instead of the D2 receptor, Gilbert says. All Food and Drug Administration-approved medications currently on the market target the D2 receptor. 

“Previous research suggests problems with dopamine, a neurotransmitter in the brain, may be linked to symptoms of Tourette syndrome,” Gilbert says. “D1 dopamine receptors play a key role.”  

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.  A limitation of the clinical trial is its three-month length. While the standard for this type of study, Gilbert says it’s important to learn if symptom improvements persist longer. 

“Our results demonstrate that ecopipam deserves more study as a viable treatment option for Tourette syndrome in young people in the future,” he says. Cincinnati Children’s will be a site for a phase III study, expected to begin enrolling children and adults with Tourette syndrome later this year.

Chemically, ecopipam is a synthetic benzazepine derivative.