FXS New Drug Phase 2/3 Clinical Results: Whole Population Analysis Fails In Patients With Complete Methylation

Recently, Zynerba Pharmaceuticals announced the top-line results of a 14-week clinical study (CONNECT-FX) using cannabidiol (CBD) for children and adolescents with brittle X syndrome (FXS)The experimental drug Zygel (ZYN002 CBD gel) failed to reach the primary endpoint and three key secondary endpoints compared to the placebo, but reached the primary endpoint in special analysis in patients with full methylation of the FMR1 geneit is known that CONNECT-FX is a randomized, double-blind, placebo-controlled 2/3 clinical study that evaluated the efficacy and safety of Zygel's behavioral symptoms in FXS patientsThe study recruited 245 FXS patients identified as completely mutated the FMR1 gene at 21 clinical trial sites in the United States, Australia and New ZealandAll patients were given a placebo in the first 2 weeks, and 33 patients did not enter the random group after entering212 patients were included in the Intentional Therapy (ITT) population, randomly divided into two groups, either treated with experimental drugs or placebos (Zygel:n?110; placebo: n-102) for 12 weeksThe dose of Zygel treatment depends on the patient's weight2 pouches of gel (about 1 pouch every 12 hours) and 4 pouches per day (about 2 pouches every 12 hours) are received twice a dayThe gel will be used to clean, dry and complete upper arm/shoulder skinBlood samples are then collected for safety analysisAn independent analytical laboratory will also conduct CGG repetition and methylation status analysisIn addition, parents/guardians and research doctors will be required to complete questionnaires and scalesAfter the final dose is administered, weekly telephone follow-up is available for a total of 4 weeksresults showed that patients in the Zygel group did not achieve statistically significant improvements in the abnormal behavior check table (ABC-CFXS) social avoidance subscale compared to placebo, and did not reach the primary endpointFrom baseline check-ups to end-of-treatment changes, Zygel patients scored on the ABC-CFXS irritability subscale, ABC-CFXS social non-reactive/sleeping subscale scores, and clinical overall impression improvements showed no statistical significance and did not reach critical secondary endpointsa complete analysis of the primary and key secondary endpoints in the CONNECT-FX study
The negative difference in treatment between NS and non-statistically significant showed an improvement in Zygel patients compared to placebo
but a special pre-planned pre-planned analysis of at least 90% methylation (full methylation) of the FMR1 gene in the trial showed that the improvement in the ABC-CFXS social avoidance sub-scale was statistically significant (p.020) and improved by 40.21% after 12 weeks of Zygel treatment compared to placebo This special analysis group included 80% of the participants in the CONNECT-FX study According to Zynerba, about 60% of FXS patients will experience full methylation Based on this results in population and symptom improvement analysis, the company plans to meet with the FDA about Zygel's regulatory approach the primary and secondary endpoint stakes of the FMR1 gene in patients , which were statistically significant compared to placebos
the difference in treatment showed that Zygel patients had improved compared to placebo
the safety of Zygel showed very good tolerance, safety consistent with previous clinical trials, and no new safety signals were found FXS is a rare genetic development already a disorder of genetic intelligence and autism spectrum disorder It is the most common genetic intellectual disability in men, with an incidence rate of about 1/3,600-4,000, and is also an important cause of female intellectual disability 1/4,000-6,000 The disease has a negative impact on synaptic function, plasticity, and neuronal connections, and can lead to a range of intellectual disorders and behavioral symptoms In the United States, about 71,000 people have FXS, and about 60 percent of those patients have full methylation of the FMR1 gene Zygel was the first and only CBD produced as a drug It is a non-pleasure-producing cannabinoid, but a patent-protected permeable-enhanced gel that can be administered by skin and circulatory skin The experimental treatment is currently being developed to treat a group of rare and ultra-rare epilepsy called developmental and epileptic encephalopathy (DEE) in children with FXS, autism spectrum disorder (ASD), 22q-(GII.missing syndrome) and so-called developmental and epileptic encephalopathy (DEE) Source: 1, Zynerba Fragile After Pivotal 2, Zynerba Pharmaceuticals Top Line Results from From FROM CONNECT-FX -FX Trial of Zygel ™ (CBD Gel) in Fragile X Syndrome Original Title: CrispX Syndrome New Drug 2/3 Clinical Outcomes: Total Population Analysis Failure, Complete Methylation PatientEffective