Zygel (cannabidiol gel) / Paragon Biosci - LARVOL DELTA

Long-term safety and tolerability of transdermal cannabidiol gel in children and adolescents with Fragile X syndrome (ZYN2-CL-017): an interim analysis of an ongoing open-label extension study. (PubMed, J Neurodev Disord) - P2/3 | "Interim analysis results of the ongoing OLE in children, adolescents, and young adults with FXS demonstrated that ZYN002 has a favorable long-term safety profile and is generally well tolerated. Clinically meaningful changes in behaviors from baseline continued to be observed during the OLE. These findings support further study of ZYN002 in patients with FXS."

Clinical • Journal • Dermatology • Fragile X Syndrome • Genetic Disorders • Pain

Efficacy and Safety of Topical 5% Cannabidiol Plus Myrcene for the Treatment of Vestibulodynia: A Multi-Centric Randomized Controlled Trial. (PubMed, Biomedicines) - " This was a randomized double-blind trial involving patients who applied a 5% cannabidiol gel with myrcene or a placebo to their vulvar vestibule for 60 days, assessing changes in dyspareunia, pain, and vestibular cotton swab test scores on a 0-10-point VAS scale...It desensitizes transient vanilloid receptor potential channels subtype 1, which are found in peripheral C-fiber nociceptors and mast cells. The results also suggest that myrcene, a terpene found in cannabis, can inhibit peripheral sensitization exerted by cannabidiol."

Journal • Neuralgia • Pain • Women's Health

Drug Interaction Study of ZYN002 Transdermal Gel and Probe Substrates (clinicaltrials.gov) - P1 | N=28 | Recruiting | Sponsor: Harmony Biosciences Management, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open

Effect of an Experimental Cannabidiol Gel on Tooth Sensitivity (clinicaltrials.gov) - P1 | N=75 | Not yet recruiting | Sponsor: Universidade Federal do Para

New P1 trial

RECONNECT: Clinical Study of Cannabidiol in Children, Adolescents, and Young Adults With Fragile X Syndrome (clinicaltrials.gov) - P3 | N=250 | Active, not recruiting | Sponsor: Zynerba Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Fragile X Syndrome • Genetic Disorders • FMR1

Drug Interaction Study of ZYN002 Transdermal Gel and Probe Substrates (clinicaltrials.gov) - P1 | N=28 | Not yet recruiting | Sponsor: Harmony Biosciences Management, Inc.

New P1 trial

Long-term Safety and Effectiveness of ZYN002 Cannabidiol Transdermal Gel in the Treatment of Irritability-Related Behavioral Symptoms in Children and Adolescents with Fragile X Syndrome: Update to Open-Label Extension Study (ZYN2-CL-017) (S31.007). (PubMed, Neurology) - P2/3 | "Dr. Nomikos has received personal compensation for serving as an employee of Harmony Biosciences."

Clinical • Journal • Behavior Disorders • Fragile X Syndrome • Genetic Disorders • Pain

Long-term Safety and Effectiveness of ZYN002 Cannabidiol Transdermal Gel in the Treatment of Irritability-Related Behavioral Symptoms in Children and Adolescents with Fragile X Syndrome: Update to Open-Label Extension Study (ZYN2-CL-017) (AAN 2025) - P2/3 | "ZYN002 has a favorable safety profile and is generally well tolerated. Secondary results support further study of ZYN002 in patients with FXS."

Clinical • Behavior Disorders • Fragile X Syndrome • Genetic Disorders • Pain

Harmony Biosciences Reports Strong 2024 Financial Results and Reiterates 2025 Net Revenue Guidance; Highlights 2025 Catalysts in Sleep/Wake and Fragile X Syndrome Development Programs (Businesswire) - "Topline data readout from Phase 3 registrational trial of ZYN002 in FXS (RECONNECT study) in Q3 2025 with potential PDUFA date in 2026; Phase 3 registrational trial in 22q11.2 deletion syndrome (22q) to initiate in 2025...EPX-100 (clemizole hydrochloride}....Topline data readout from Phase 3 registrational trial in Dravet syndrome (ARGUS Study) anticipated in 2026; Topline data for Phase 3 registrational trial in patients with Lennox-Gastaut syndrome (LIGHTHOUSE study) anticipated in 2026."

New P3 trial • P3 data: top line • Epilepsy • Fragile X Syndrome

Long-Term Safety and Sustained Efficacy of ZYN002 Cannabidiol Transdermal Gel in the Treatment of Irritability-Related Behavioral Symptoms in Children, Adolescents, and Young Adults With Fragile X Syndrome: Update to Open-Label Extension Study (AACAP 2024) - P2/3 | "Consistent with previous analyses of the OLE data, ZYN002 has been generally well tolerated and results have continued to support its effectiveness in improving behavioral symptoms of FXS.DBD, ND, PTA"

Clinical • Behavior Disorders • Fragile X Syndrome • Genetic Disorders • Pain

2024 Update to the Long-term Safety and Sustained Efficacy of ZYN002 Cannabidiol Transdermal Gel in the Treatment of Behavioral Symptoms in Children, Adolescents, and Young Adults with Fragile X Syndrome (ZYN2-CL-017) (NFXF-FXC 2024) - "The results being presented are from the open-label extension (OLE) trial ZYN2-CL-017. The data collected through 31-January-2024 will assess both safety and efficacy in patients entering the OLE from the CONNECT-FX, FAB-C, and RECONNECT trials with forthcoming results and conclusions."

Clinical • Fragile X Syndrome • Genetic Disorders

RECONNECT: Clinical Study of Cannabidiol in Children, Adolescents, and Young Adults With Fragile X Syndrome (clinicaltrials.gov) - P3 | N=204 | Recruiting | Sponsor: Zynerba Pharmaceuticals, Inc. | Trial completion date: Mar 2024 ➔ May 2025 | Trial primary completion date: Mar 2024 ➔ May 2025

Trial completion date • Trial primary completion date • Fragile X Syndrome • Genetic Disorders • FMR1

HARMONY BIOSCIENCES TO PRESENT RESULTS FROM BEHAVIORAL STUDY IN 22Q11.2 DELETION SYNDROME AT AMERICAN COLLEGE OF NEUROPSYCHOPHARMACOLOGY ANNUAL MEETING (PRNewswire) - "Harmony Biosciences Holdings, Inc...will present caregiver-reported impacts of 22q11.2 deletion syndrome (22q) and data from the Phase 2 INSPIRE trial at the American College of Neuropsychopharmacology Annual Meeting from December 3-6, 2023."

P2 data • CNS Disorders • Genetic Disorders

RECONNECT: Clinical Study of Cannabidiol in Children, Adolescents, and Young Adults With Fragile X Syndrome (clinicaltrials.gov) - P3 | N=204 | Recruiting | Sponsor: Zynerba Pharmaceuticals, Inc. | Trial completion date: Dec 2023 ➔ Mar 2024 | Trial primary completion date: Sep 2023 ➔ Mar 2024

Trial completion date • Trial primary completion date • Fragile X Syndrome • Genetic Disorders • FMR1

Long-Term Safety and Sustained Efficacy of ZYN002 Cannabidiol Transdermal Gel in the Treatment of Behavioral Symptoms in Children and Adolescents With Fragile X Syndrome (ZYN2-CL-017) (AACAP 2023) - "In patients with complete FMR1 methylation, ZYN002 led to sustained improvement in SA. The results from this trial continue to support the effectiveness of ZYN002 in patients with complete FMR1 methylation."

Clinical • Fragile X Syndrome • Genetic Disorders • Pain • FMR1

Analgesic and Anti-Inflammatory Effects of 1% Tropical Cannabidiol Gel in Animal Models. (PubMed, Cannabis Cannabinoid Res) - " The topical administration of 1% CBD gel is a potentially effective candidate for an anti-inflammatory agent. Candidate for an anti-inflammatory agent."

Journal • Preclinical • Immunology • Inflammation • Pain • Rheumatology

Development of an UHPLC-MS/MS method to determine cutaneous biodistribution of cannabidiol after topical application of cannabidiol gel assisted by iontophoresis. (PubMed, Biomed Chromatogr) - "Positive-ion mode with multiple reaction monitoring detection was used to quantify cannabidiol (m/z 315.1 → 193.1) while diphenhydramine (m/z 256.3 → 167.08) served as the internal standard. The intra-day and inter-day RSDs of cannabidiol were all <2%. A cryo-sectioning technique combined with the UHPLC-MS/MS method was used to successfully determine cannabidiol levels in a series of very thin skin layers."

Journal • Dermatology

An Open-Label Trial Assessing Short- And Long-Term Tolerability and Efficacy of ZYN002 (Cannabidiol) Administered as a Transdermal Gel to Children and Adolescents with 22q11.2 Deletion Syndrome (INSPIRE) and Long-Term Safety and Sustained Efficacy of ZYN002 Cannabidiol Transdermal Gel in the Treatment of Behavioral Symptoms in Children and Adolescents with Fragile X Syndrome (ZYN2-CL-017) (ASCP 2023) - "ZYN002 was well tolerated over a median of 20 months. In patients with complete FMR1 gene methylation, ZYN002 led to sustained improvement in Social Avoidance, a key behavioral symptom of FXS, following initial improvement seen after 12 weeks of double-blind therapy. The results from this OLE trial continue to support the effectiveness of ZYN002 in patients with complete FMR1 gene methylation."

Clinical • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Depression • Mood Disorders • Pain • Psychiatry • FMR1

Long-Term Safety and Sustained Efficacy of ZYN002 Cannabidiol Transdermal Gel in the Treatment of Behavioral Symptoms in Children and Adolescents with Fragile X Syndrome (ZYN2-CL-017) (ASCP 2023) - "ZYN002 was well tolerated over a median of 20 months. In patients with complete FMR1 gene methylation, ZYN002 led to sustained improvement in Social Avoidance, a key behavioral symptom of FXS, following initial improvement seen after 12 weeks of double-blind therapy. The results from this OLE trial continue to support the effectiveness of ZYN002 in patients with complete FMR1 gene methylation."

Clinical • CNS Disorders • Pain • FMR1

An Open-Label Trial Assessing Short- And Long-Term Tolerability and Efficacy of ZYN002 (Cannabidiol) Administered as a Transdermal Gel to Children and Adolescents with 22q11.2 Deletion Syndrome (INSPIRE) (ASCP 2023) - "INSPIRE provides initial evidence suggesting a positive risk–benefit profile for ZYN002 in improving behavioral and anxiety-related symptoms in children and adolescents with 22q when added on top of stable standard of care. Further studies are warranted."

Clinical • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Depression • Mood Disorders • Psychiatry

Open Label Extension to Assess the Long-Term Safety and Tolerability of ZYN002 in Children and Adolescents With FXS (clinicaltrials.gov) - P2/3 | N=450 | Enrolling by invitation | Sponsor: Zynerba Pharmaceuticals, Inc. | Trial completion date: May 2027 ➔ Aug 2027 | Trial primary completion date: May 2027 ➔ Aug 2027

Trial completion date • Trial primary completion date • Fragile X Syndrome • Genetic Disorders

Medicinal Cannabis for Paediatric Developmental, Behavioural and Mental Health Disorders. (PubMed, Int J Environ Res Public Health) - "Synthetic, transdermal cannabidiol gel has demonstrated efficacy for reducing social avoidance in a sub-group of children with Fragile X syndrome. Studies of medicinal cannabis are planned or underway for children and/or adolescents with autism, intellectual disability, Tourette's syndrome, anxiety, psychosis, anorexia nervosa and a number of specific neurodevelopmental syndromes. High quality evidence from double-blind placebo-controlled trials is needed to guide clinical practice."

Journal • Review • Anorexia • Autism Spectrum Disorder • CNS Disorders • Developmental Disorders • Fragile X Syndrome • Genetic Disorders • Mental Retardation • Mood Disorders • Pediatrics • Psychiatry • Tourette Syndrome

INSPIRE: Open-Label Study of ZYN002 Administered as a Transdermal Gel to Children and Adolescents With 22q11.2 Deletion Syndrome (clinicaltrials.gov) - P1/2 | N=20 | Completed | Sponsor: Zynerba Pharmaceuticals, Inc. | Active, not recruiting ➔ Completed

Trial completion • Immunology • Primary Immunodeficiency

Role of the endocannabinoid system in fragile X syndrome: potential mechanisms for benefit from cannabidiol treatment. (PubMed, J Neurodev Disord) - "Moreover, cannabidiol affects DNA methylation, serotonin 5HT signal transduction, gamma-aminobutyric acid receptor signaling, and dopamine D and D receptor signaling, which may contribute to beneficial effects in patients with FXS. Consistent with these proposed mechanisms of action of cannabidiol in FXS, in the CONNECT-FX trial the transdermal cannabidiol gel, ZYN002, was associated with improvements in measures of social avoidance, irritability, and social interaction, particularly in patients who are most affected, showing ≥90% methylation of the FMR1 gene."

Journal • Review • Fragile X Syndrome • Genetic Disorders • FMR1

A randomized, controlled trial of ZYN002 cannabidiol transdermal gel in children and adolescents with fragile X syndrome (CONNECT-FX). (PubMed, J Neurodev Disord) - P2/3 | "In CONNECT-FX, ZYN002 was well tolerated in patients with FXS and demonstrated evidence of efficacy with a favorable benefit risk relationship in patients with ≥ 90% methylation of the FMR1 gene, in whom gene silencing is most likely, and the impact of FXS is typically most severe."

Journal • Behavior Disorders • Fragile X Syndrome • Genetic Disorders • Pain • FMR1