Tuesday, April 16, 2024

Ecopipam for Tourette syndrome

Ecopipam reduced the number of tics and the level of daily interference they cause in children and adolescents with Tourette syndrome, according to the results of a re-analysis of the phase 2b D1AMOND study presented in April at the AAN Annual Meeting in Denver.

“If this finding is confirmed in future studies, we could tell kids and their parents that this medication cuts down on both the number of different tics and how much they interfere on a daily basis," said Donald L. Gilbert, MD, FAAN, professor of pediatrics and neurology at Cincinnati Children's Hospital Center, who presented the findings.

The findings provide more specificity on how ecopipam works in Tourette syndrome, building on previously reported results of the international, multicenter D1AMOND study in which 153 children with the condition were randomized to ecopipam or placebo. The study found that patients treated with ecopipam had a significant reduction in tic scores based on the Yale Global Tic Severity Scale at 12 weeks compared with placebo without the common side effects, such as weight gain, seen with conventional drugs used in this setting.

These conventional drugs block the dopamine D2 receptor, whereas ecopipam is the first in its class to block the dopamine D1 receptor. Dr. Gilbert said if phase 3 clinical trial results confirm the efficacy of ecopipam to treat unwanted or involuntary movements, “there may be more ways in the future to down-modulate dopamine signaling via other receptors in ways that may help our patients function better."

By providing more specificity on how ecopipam affects tics, Gilbert and colleagues hope to offer clearer communication to children and their parents on what they can expect with the drug if approved.

“When you are treating a neurologic condition for which the clinical outcome is rated on a scale, it may be helpful to think about what that scale is actually capturing," said Dr. Gilbert. “Can the improvement on the scale be re-analyzed in a way that allows for simple communication about possible “bad to good" benefits?"

Dr. Gilbert and colleagues did just that in their reanalysis. They recategorized each child's Yale Global Tic Severity Scale scores from the original number (1 to 5 for each tic characteristic subscale) into “bad" (representing a rating of 3 to 5) or “good" (rating from 0 to 2) for each tic characteristic. For each category, they then calculated how likely it was for the score on ecopipam to go from “bad" at baseline to “good" at 12 weeks and compared this with outcomes for those on placebo.

They found that ecopipam was associated with a greater probability of going from a bad to a good score for the number of tics and level of daily interference compared with placebo. When looking at motor tics only, the largest reductions statistically were in intensity scores following by number, frequency, and daily interference. For vocal tics, the largest reduction was seen in complexity scores.

Dr. Gilbert cited the fact that fewer kids who start with vocal tic subscores in the “bad" range as one challenge to doing a re-analysis of the data as “it would take a larger number of kids in a study to get an accurate estimate of “bad to good" changes for vocal tics."

Jeremiah M. Scharf, MD, PhD, a behavioral neurologist and director of the Tic Disorders Unit at Massachusetts General Hospital, said the findings were encouraging because they offer more positive information about ecopipam as a promising medication for people with Tourette syndrome.

“This is certainly the type of medication we would be interested in using if medication is required," said Dr. Scharf, who was not involved with the study. He stressed that front-line behavioral therapy is not always sufficient for children with Tourette syndrome, and a gap exists in available medical treatment, given the major side effects seen with the current dopamine D2 receptor blockers.

“This is very exciting for our field," he said, adding, however, that “ultimately, it's the phase 3 trial where the rubber meets the road."


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