Ecopipam Meets Primary and Secondary End Points in Phase 3 Study for Tourette Syndrome

Frederick Munschauer, MD

(Credit: Emalex Biosciences)

New topline data from the phase 3 D1AMOND study (NCT05615220) showed that Emalex Biosciences’ ecopipam, an investigational dopamine-1 receptor antagonist, met its primary and secondary end points among patients with Tourette syndrome (TS). The company noted that it plans to meet with the FDA and other global health authorities to discuss a potential new drug application submission for ecopipam in TS later this year.¹

For the primary efficacy end point, measured by the time to relapse among pediatric patients, results indicated that 41.9% of those randomized to ecopipam experienced a relapse, compared with 68.1% of those on placebo (hazard ratio, 0.5 [0.3-0.8]; P = .0084). As for the secondary efficacy end point, which assessed time to relapse in both pediatric and adult participants after randomization, findings showed that 41.2% of patients in the ecopipam group relapsed, compared with 67.9% in the placebo group (hazard ratio, 0.5 [0.3-0.8]; P = .0050).

"Everyone at Emalex and our partners, including the physician investigators, are thrilled with the results from our registrational Phase 3 study. It’s very difficult to design and conduct clinical studies for this indication and not many compounds have succeeded in late-stage trials," Frederick Munschauer, MD, chief medical officer at Emalex Biosciences, told NeurologyLive^® in a recent interview. "We now have two successful adequate and well-controlled clinical studies that we believe will support marketing authorization applications. Our first registrational trial established the efficacy of ecopipam in Tourette syndrome with a favorable safety profile. This second registrational trial supports that efficacy and confirms the durability of the treatment effect over a longer trial period. We were also heartened to see that the tolerability and safety profile was similar between the two registrational trials."

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In the phase 3 study, researchers enrolled 167 pediatric and 49 adult patients with TS across study sites in the US, Canada, and the European Union. Participants who showed significant improvement in vocal and motor tics after a 12-week open-label treatment with ecopipam were then randomly assigned to either continue ecopipam or switch to a placebo during a 12-week double-blind withdrawal phase.

"If approved, ecopipam would become the first and only new class of FDA-approved medicine to treat Tourette syndrome in 56 years. Haloperidol, a D2 receptor antagonist, was first approved for Tourette in 1969. Aripiprazole and Pimozide followed afterward but are the same class of medicine," Munschauer added. "Existing treatments inadequately control the symptoms of Tourette and some are associated with unacceptable side effects that limit utilization."

TS is a long-term neurodevelopmental disorder that begins in childhood and is marked by motor and vocal tics. The condition is linked to both higher mortality rates and considerable health challenges. For most individuals, TS significantly affects daily physical activities and social interactions. In terms of safety outcomes in the phase 3 trial, ecopipam was generally well tolerated and the most common adverse events related to ecopipam therapy were somnolence (10.2%), insomnia (7.4%), anxiety (6.0%), fatigue (5.6%), and headache (5.1%).

“Tourette syndrome, for many, is a serious disease associated with physical, psychological, and social difficulties that cumulatively adversely affect children in their formative years. There is a clear need for new treatments with demonstrated efficacy and better safety and tolerability than current medications," Munschauer said to NeurologyLive. "We look forward to publishing our full results and working with the FDA, and other health authorities, to discuss applications for marketing approval. We expect to submit an NDA to the US Food and Drug Administration by the end of 2025 and plan to submit ex-US marketing authorization applications in 2026. Our ultimate hope is to bring a new therapy to people suffering from this serious neurodevelopmental disease."

REFERENCES
1. Emalex Biosciences’ Lead Candidate Meets Primary and Secondary Endpoints in Phase 3 Tourette Syndrome Study. News Release. Emalex Biosciences. Published February 25, 2025. Accessed February 25, 2025. https://emalexbiosciences.com/news/emalex-biosciences-lead-candidate-meets-primary-and-secondary-endpoints-in-phase-3-tourette-syndrome-study/