New research highlights ecopipam's effectiveness in reducing Tourette syndrome symptoms and relapse risk in children, offering a promising treatment alternative.
New findings from a phase 3 randomized withdrawal trial suggest that continued treatment with ecopipam (Emalex Biosciences), an investigational dopamine D1 receptor antagonist, significantly reduces the risk of symptom relapse in children and adolescents with Tourette syndrome (TS).1 The therapy, previously shown to reduce tics with a
The data were presented at the
In the pediatric population (ages 6 to <18 years), continued ecopipam use resulted in a 50% risk reduction for relapse compared with placebo (HR, 0.5; 95% CI, 0.3-0.8; P = .008), based on time from randomization to relapse—defined as a 50% or greater reduction in the YGTSS-TTS score achieved at week 12 of the open-label phase. A similar 50% reduction in relapse risk was observed in the overall randomized cohort, which included both pediatric and adult participants (HR, 0.5; 95% CI, 0.3-0.8; P = .005).
In total, the trial enrolled 216 patients aged 6 years and older with TS, who entered a 12-week open-label phase with ecopipam titrated up to a target dose of 1.8 mg/kg/day. At weeks 8 and 12, patients who achieved a 25% or greater improvement from baseline on the Yale Global Tic Severity Scale Total Tic Score (YGTSS-TTS) were randomized into a 12-week double-blind withdrawal phase to continue ecopipam or switch to placebo.
Of the 104 participants randomly assigned to groups, 90 were pediatric patients. Among those assigned to continue ecopipam (n = 51), 84.3% were under the age of 18 years, and 72.5% were male. In the placebo group (n = 53), 88.7% were pediatric and 66.0% were male.
Adverse events (AEs) reported during the 24-week study period were generally mild to moderate and consistent with previous trials. The most commonly reported AEs in patients treated with ecopipam were somnolence (11.1%), anxiety (9.7%), headache (9.7%), insomnia (8.8%), worsening of tics (7.9%), and fatigue (6.5%). No serious safety concerns were noted by Tomczak et al.
Currently, the pharmacologic treatments for TS—including antipsychotics and dopamine receptor antagonists—carry various risks including weight gain, metabolic syndrome, and drug-induced movement disorders. Ecopipam’s distinct mechanism as a selective dopamine D1 receptor antagonist offers a potential alternative that avoids many of these complications.
During the first Stuttering Treatment and Research Society (STARS) meeting, founder Gerald Maguire, MD, sat down to discuss the limited but evolving treatment landscape, ways clinicians can help treat comorbidities in patients with stuttering, and the importance of distinguishing stuttering from anxiety disorders.
“This phase 3 trial provided confirmatory evidence that clinically meaningful improvements in TS symptoms were maintained with continued ecopipam treatment, which was generally well tolerated,” Tomczak et al concluded.1
Earlier this year, open-label extension (OLE) data from the aforementioned phase 2b study showed that treatment with investigational ecopipam was safe and effective in TS over a 12-month period, showing reduced TS symptom severity and improved quality of life (QOL) in children and adolescent patients.2 The OLE data included 121 patients administered at least 1 dose of ecopipam at 1.8 mg/kg/day who previously completed the phase 2b randomized, placebo-controlled, 12-week trial. Of these, 80 (66.1%) completed the OLE.
Throughout the 12-month period, ecopipam continued to show a safe and tolerable profile, with the most common AEs being nasopharyngitis (14.0%) and anxiety (9.0%), most of which were mild or moderate in nature. Additional safety findings showed that AEs of special interest were found in nearly one-fifth (19.8%) of the cohort.
Dose reductions caused by AEs were reported for 6 patients (100 mg to 75 mg, n = 3; 75 mg to 12.5 mg, n = 1; not determined, n = 2), all of whom received placebo during the phase 2b trial. Notably, suicidal ideation was reported in 3 patients (2.5%), though no suicidal behavior was reported, and no dose changes for these patients were deemed necessary.
Over the 12-month extension, there were no significant changes in glycated hemoglobin (mean change, 0.03; SD, 0.31; P = .60), total cholesterol (0.2 mmol/L; SD, 0.7; P = 0.14), triglycerides (0.09 mmol/L; SD, 0.64; P = 0.46), diastolic blood pressure (0.9 mm Hg; SD, 10.0; P = 0.44), or systolic blood pressure (0.3 mm Hg; SD, 11.5; P = 0.85). Notably, those treated with ecopipam reported no significant changes in body mass index z-score (mean change, 0.05; SD, 0.43; P = .35).
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