ecopipam (PSYRX 101) / Paragon Biosci - LARVOL DELTA

QUESTIONS THAT MAKE YOU TIC: A TOURETTE'S DISORDER AND RELATED DISORDERS UPDATE (AACAP 2025) - "Cathy L. Budman, MD, will provide an overview of TD pharmacology and focus on new, promising interventions, including ecopipam and gemlapodect. This Symposium highlights novel, practical, clinically relevant advances in TD and related disorders' conceptualization and treatment interventions.TICD, TRIC, NI"

ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Inflammation • Mental Retardation • Movement Disorders • Psychiatry • Tic Disorders • Tourette Syndrome

Efficacy of Ecopipam on Motor and Phonic Tics in Tourette's Disorder: Data From a Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial (AACAP 2025) - "Ecopipam significantly improved both motor and phonic tics in children, adolescents, and adults with TD and was generally well tolerated.TD"

Clinical • P3 data • CNS Disorders • Fatigue • Insomnia • Mood Disorders • Movement Disorders • Pediatrics • Psychiatry • Sleep Disorder • Tourette Syndrome

Update on Pharmacology in Tourette's Disorder (AACAP 2025) - "There are only 3 pharmacological interventions FDA-approved for TD: pimozide, haloperidol, and aripiprazole, and as such, most treatments are used off-label...She will also describe recent trials that did not meet their primary end points (eg, deutetrabenazine, nabiximols), but may still hold promise for certain individuals/subgroups with TD... There is a great need for new medications for TD that are as effective for tics as antipsychotics, but without the potential short and long-term side effects associated with typical and atypical antipsychotics. Recently, new medications currently in Phase IIb and III trials are showing great promise!.TD, TICD, PPC"

CNS Disorders • Mental Retardation • Movement Disorders • Psychiatry • Tourette Syndrome

Efficacy and Safety of Ecopipam for Tourette Syndrome (TS): Results From a Phase 3, Randomized, Double-Blind, Placebo-Controlled Withdrawal Trial (MDS Congress 2025) - "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."

Clinical • P3 data • CNS Disorders • Insomnia • Mood Disorders • Movement Disorders • Psychiatry • Sleep Disorder • Tourette Syndrome

Determination of the Minimal Clinically Important Difference in the Yale Global Tic Severity Scale Total Tic Score in a Pediatric Population With Tourette Syndrome Receiving Pharmacotherapy (MDS Congress 2025) - " The study included data from 2 trials of the investigational drug ecopipam (1 randomized controlled trial and its open-label extension)... This analysis is the first to establish the MCID for YGTSS in a pediatric population with TS receiving pharmacotherapy. Whether using CGI-TS-S or CGI-TS-I as the anchor, a 25% reduction in YGTSS scores was an appropriate minimum threshold to define clinically meaningful improvement in this population. Results provide an objective threshold for classifying clinically meaningful improvement in children/adolescents receiving pharmacotherapy for TS in clinical practice."

Clinical • CNS Disorders • Movement Disorders • Tourette Syndrome

Large nesting expression in deer mice remains stable despite dopamine and adenosine modulation: insights into the psychobiology of compulsive-like rigidity (ECNP 2025) - "While selective serotonin reuptake inhibitors (SSRIs), e.g., escitalopram (ESC), are regarded as first line pharmacotherapy, treatment resistance remains a clinical dilemma. We show that NNB, as opposed to LNB, inflates over time irrespective of exposure (p = 0.0008), with LNB expression remaining stable. However, nesting inflation in NNB mice exposed to ecopipam trended towards being the least compared to all other treatment groups (0.05 > p 0.8). Collectively, our data support earlier findings that LNB is an evolutionary conserved behaviour borne from a neurobiological underpinning that drives maximal cortico-striatal activation."

Preclinical • CNS Disorders • Mood Disorders • Obsessive-Compulsive Disorder • Psychiatry

Combined inhibition of dopamine D1/D2 receptors induces cognitive and emotional dysfunction through oxidative stress and dopaminergic neuron damage. (PubMed, Front Behav Neurosci) - "In this study, we aimed to investigate the dose-dependent effects of co-DR1/2I (combined administration of dopamine receptor 1 inhibitor SCH39166 and dopamine receptor 2 inhibitor raclopride) on oxidative stress, learning, memory, emotion, and motor function in the substantia nigra, striatum, and hippocampus of mice...This is the first study to demonstrate that co-DR1/2I triggers cognitive and emotional dysfunction by exacerbating oxidative stress and dopaminergic neuronal damage, thereby advancing our understanding of the neurotoxic mechanisms of dopamine receptor antagonists. Future studies are needed to explore targeted antioxidant therapies and receptor-selective modulation strategies to reduce the side effects."

Journal • Alzheimer's Disease • CNS Disorders • Mental Retardation • Mood Disorders • Movement Disorders • Parkinson's Disease • Psychiatry

EBS-101-TD-391: A Study to Evaluate Long-term Safety of Ecopipam Tablets in Children, Adolescents and Adults With Tourette's Disorder (clinicaltrials.gov) - P3 | N=150 | Active, not recruiting | Sponsor: Emalex Biosciences Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Movement Disorders • Tourette Syndrome

EBS-101-TD-392: Expanded Access Program for Treatment With Ecopipam for Tourette's Disorder (clinicaltrials.gov) - P=N/A | N=0 | Temporarily Not Available | Sponsor: Emalex Biosciences Inc.

New trial • Tourette Syndrome

Tourette Syndrome and Tic Disorders. (PubMed, Continuum (Minneap Minn)) - "A first-in-class compound called ecopipam met the primary endpoint for tic reduction and was well-tolerated, and may be a promising new treatment for Tourette syndrome...Educating patients about the natural history and expected course of the disease is the most important first step in management. Choosing a treatment based on comorbidities, tic severity, and patient preference is crucial for a beneficial outcome."

Journal • Review • Infectious Disease • Movement Disorders • Novel Coronavirus Disease • Tic Disorders • Tourette Syndrome

Regulation of working memory switches from striatal dopamine D2-receptor to D1-receptor neurons under high cognitive load. (PubMed, PLoS Biol) - "Additionally, treatment with the D1R antagonist SCH39166, but not the D2R antagonist Sulpiride mitigates these impairments. Collectively, our findings propose a "relay" model wherein cognitive load-dependent WM control switches from DMS D2R- to D1R-neurons, offering nuanced, complementary, and inhibitory regulation of WM maintenance and retrieval. This study suggests potential strategies to enhance WM by promoting a suppressive state in DMS and to increase WM capacity through specific modulation of DMS D1R-neurons."

Journal • DRD2

Safety and Effect of 12-Month Ecopipam Treatment in Pediatric Patients with Tourette Syndrome. (PubMed, Mov Disord Clin Pract) - "Twelve months of ecopipam dosing was well tolerated during this study and no new adverse events were detected. Compared to baseline, significantly reduced TS symptom severity and improved QOL were observed in children and adolescents."

Journal • CNS Disorders • Depression • Developmental Disorders • Infectious Disease • Mood Disorders • Movement Disorders • Pediatrics • Psychiatry • Tic Disorders • Tourette Syndrome

Determining Clinically Meaningful Improvement in Children and Adolescents with Tourette Syndrome Receiving Pharmacotherapy. (PubMed, J Child Adolesc Psychopharmacol) - "Materials and Analyses used data from two clinical trials of ecopipam (a randomized controlled trial and its open-label extension)...Whether using CGI-TS-S or CGI-TS-I as the anchor, a 25% reduction in YGTSS scores was a generally appropriate minimum threshold to define clinically meaningful improvement in this population. Findings offer an objective threshold for classifying clinically meaningful improvement in children and adolescents receiving pharmacotherapy for TS in clinical practice."

Journal • Movement Disorders • Pediatrics • Tic Disorders • Tourette Syndrome

EBS-101-TD-391: A Study to Evaluate Long-term Safety of Ecopipam Tablets in Children, Adolescents and Adults With Tourette's Disorder (clinicaltrials.gov) - P3 | N=150 | Recruiting | Sponsor: Emalex Biosciences Inc. | Trial primary completion date: Nov 2024 ➔ Dec 2026

Trial primary completion date • Movement Disorders • Tourette Syndrome

D1AMOND: Ecopipam Tablets to Study Tourette's Disorder in Children, Adolescents and Adults (clinicaltrials.gov) - P3 | N=216 | Completed | Sponsor: Emalex Biosciences Inc. | Active, not recruiting ➔ Completed

Trial completion • Tourette Syndrome

Ecopipam Induced Hyperkalemia in an 18-Year-Old Male (NKF-SCM 2025) - "This case emphasizes the need for ongoing safety monitoring in the use of any investigational medication and identifies a potentially novel adverse effect associated with ecopipam.Conclusion This case highlights a novel adverse effect of ecopipam, an investigational Tourette Syndrome treatment, causing hyperkalemia due to renal tubular dysfunction. Monitoring renal function and serum potassium is crucial to mitigate risks, emphasizing the need for thorough safety assessments in clinical trials."

CNS Disorders • Congenital Adrenal Hyperplasia • Developmental Disorders • Endocrine Disorders • Hypotension • Movement Disorders • Nephrology • Psychiatry • Renal Disease • Tourette Syndrome

Changes in Metabolic Parameters and Determination of Minimal Clinically Important Difference in YGTSS-TTS Using Data From the Randomized Phase 2b and Open-Label Extension Studies of Ecopipam For Tourette Syndrome (AAN 2025) - "Ecopipam did not adversely affect parameters associated with an increased risk of metabolic syndrome. ROC analysis suggested that ≥25% reduction in YGTSS-TTS is an appropriate minimum threshold to define clinically meaningful improvement (MCID) in this patient population."

Clinical • P2b data • Metabolic Disorders • Movement Disorders • Tourette Syndrome

The Effect of Ecopipam and its Metabolites on Cardiac Repolarization, QTcF (AAN 2025) - "Design/A randomized, double-blind, placebo-controlled, 4-way crossover study with single doses of ecopipam 179.2 mg, ecopipam 537.6 mg, placebo, and open-label moxifloxacin 400 mg was conducted. A 10 msec increase in ΔΔQTcF can be ruled out at ecopipam 179.2 mg, the therapeutic dose. A 10 msec increase in ΔΔQTcF interval cannot be ruled out at the high clinical drug exposure (ecopipam 179.2 mg + a general UGT inhibitor), but the effect is small. After a 537.6 mg ecopipam dose, increases in the ΔΔQTcF interval up to 20.4 msec are predicted."

Tourette Syndrome • CYP3A4 • UGT1A9

SNX19 Interacts with Caveolin-1 and Flotillin-1 to Regulate D1R Endocytosis and Signaling. (PubMed, Biomedicines) - "In mouse RPTCs transfected with wild-type (WT) Snx19, fenoldopam (FEN), a D1-like receptor agonist, increased the colocalization of SNX19 with caveolin-1 and flotillin-1. FEN also increased the co-immunoprecipitation of SNX19 with caveolin-1 and flotillin-1, effects that were prevented by SCH39166, a D1-like receptor antagonist...Nocodazole, a microtubule depolymerization inhibitor, interfered with the FEN-mediated increase in the colocalization between SNX19 and D1R. SNX19 contains caveolin-1 and flotillin-1 binding motifs, which play an important role in D1R endocytosis and signaling."

Journal • CAV1 • FLOT1 • SNX

Food-effect Study of Ecopipam Pharmacokinetics (clinicaltrials.gov) - P1 | N=25 | Completed | Sponsor: Emalex Biosciences Inc. | Active, not recruiting ➔ Completed

Trial completion

D1 dopamine receptor antagonists as a new therapeutic strategy to treat autistic-like behaviours in lysosomal storage disorders. (PubMed, Mol Psychiatry) - "Neither risperidone nor methylphenidate improves ALBs in the MPS-IIIA mouse model, with the former showing increased cataleptic (extrapyramidal-like) side effects compared to littermate wild-type animals. In contrast, ecopipam, a D1 antagonist already used in the clinic for other neuropsychiatric disorders, rescues ALBs, cognition, D1 hyperactivity, and does not worsen neurodegenerative signs. These results align with recent evidence highlighting the clinical relevance of D1 antagonists for neuropsychiatric disorders and pave the way for their use in managing psychotic symptoms in neurodegenerative disorders such as dementia with Lewy bodies."

Journal • Alzheimer's Disease • CNS Disorders • Dementia • Hunter Syndrome • Inflammation • Lewy Body Disease • Lysosomal Storage Diseases • Mental Retardation • Metabolic Disorders • Psychiatry • Rare Diseases • Sleep Disorder • DRD2

Safety and Efficacy of Ecopipam in Patients with Tourette Syndrome: A Systematic Review and Meta-analysis. (PubMed, CNS Drugs) - "Ecopipam is effective in reducing the severity of tics in subjects with TS and has a good safety profile. However, only a limited number of studies were included in the review, with some having small sample sizes and short duration of follow-up."

Journal • Retrospective data • Review • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Movement Disorders • Psychiatry • Tourette Syndrome

Food-effect Study of Ecopipam Pharmacokinetics (clinicaltrials.gov) - P1 | N=25 | Active, not recruiting | Sponsor: Emalex Biosciences Inc. | Not yet recruiting ➔ Active, not recruiting

Enrollment closed

Emerging therapeutic approaches for Tourette syndrome and other tic disorders - a systematic review of current clinical trials. (PubMed, Eur Child Adolesc Psychiatry) - "Potential candidates include the dopamine D1 antagonist ecopipam, the phosphodiesterase inhibitor gemlapodect, and cannabis-based therapies. Despite the range of research activities underway, the overall landscape remains limited. In this report we will discuss the findings, current developments, and relevant aspects concerning future research including clinical, scientific, and patient perspectives."

Journal • Review • CNS Disorders • Developmental Disorders • Movement Disorders • Psychiatry • Tic Disorders • Tourette Syndrome • Transplantation

D1AMOND: Ecopipam Tablets to Study Tourette's Disorder in Children, Adolescents and Adults (clinicaltrials.gov) - P3 | N=196 | Active, not recruiting | Sponsor: Emalex Biosciences Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Tourette Syndrome