Aevi Genomic Medicine Presents Updated Results from SAGA Trial of AEVI-001 at the 6th World Congress on ADHD
-- New results clarify a path forward for the continued development of AEVI-001 in ADHD patients and potential future development in other neurodevelopmental disorders --
- Identification of nine genes that are predictive of clinically meaningful and statistically significant response [ADHD-Rating Scale (ADHD-RS) reduction of 17.6, p < .005] in the SAGA trial. These genes include certain glutamate metabotropic receptors (GRM) and neurodevelopmental genes and are found in approximately 10% of pediatric ADHD patients.1
- One of the neurodevelopmental genes, contactin-4 (CNTN4) previously identified as important in Autism Spectrum Disorder (ASD), was highly enriched in the responder population (43%) and represents approximately 5% of pediatric ADHD patients.1
- CNTN4 mutation phenotype is more severe with a higher prevalence of emotional dysregulation, including: anger control, risk taking, inappropriate movements and sounds.
- All CNTN4 mutation positive patients on treatment (n=6) had clinically meaningful and statistically significant response to AEVI-001 (ADHD-RS reduction of 20.8, p=.03).
"The SAGA trial post hoc responder analysis represents a novel genomic approach to psychiatric drug development. Genetic stratification of patient subpopulations appears to identify patients with specific gene mutations who are more likely to respond to AEVI-001," said
"This is an exciting and novel finding in ADHD, that CNTN4 mutations have a meaningful prevalence in ADHD and are highly associated with a response to AEVI-001. CNTN4 mutations and deletions have been previously associated with neurodevelopmental delay, ASD, and other neuropsychiatric conditions. ADHD and ASD are frequently co-morbid with each other, and these new data suggest that CNTN4 mutations may be a common genetic link for these diseases. I look forward to working with the Company to study this further in children with mutation positive ADHD as well as the potential to study AEVI-001 in patients with ASD."
The recent analysis demonstrates that of the 42 patients with a mutation in one of nine genes (n=18 patients on treatment, n=24 patients on placebo), 89% of patients on treatment (n=16) had a clinically meaningful and statistically significant response to AEVI-001 in the SAGA trial (defined as a 30% or greater reduction in ADHD-RS score from baseline), vs 21% on placebo (p < .0001). Patients on treatment had a reduction in ADHD-RS of 17.6 versus 5.9 on placebo (p < .005). This subset of patients had mutations in the CNTN4 gene as well as certain GRM and neurodevelopmental genes.
More specifically, 18 patients with copy-number variation (CNV) mutations in CNTN4 were enrolled in the SAGA trial (six patients on treatment and 12 patients on placebo). 100% of CNTN4 positive patients (n=6) treated with AEVI-001 had a reduction in ADHD-RS of > 30% vs. 25% of placebo patients (p=.0027). The magnitude of response of CNTN4 positive patients treated with AEVI-001 was a 20.8 point reduction in ADHD-RS vs. an 8.9 point reduction in ADHD-RS in patients on placebo (p=.03).
"The robust response of CNTN4 mutation-positive ADHD adolescents to AEVI-001 in the SAGA trial suggests that CNTN4 associated ASD may be successfully treated with AEVI-001," said
Based on the Company's study "Glutamatergic Network Gene Mutations in Children and Adolescents with ADHD (Phenotype/Genotype study)," approximately 10% of ADHD patients bear a CNV mutation in one of the nine genes. As found in the SAGA trial, the most prevalent gene in this phenotype-genotype study was CNTN4, with an approximate prevalence in ADHD of nearly 5%.
Patients bearing mutations in CNTN4 exhibited a unique and more severe ADHD phenotype. Compared to other ADHD patients, they had significantly higher rates of parent-reported behaviors suggestive of emotional dysregulation, including: disruptive behavior, anger control, risk-taking, and inappropriate movements and sounds.
The Company will present two posters at the
Title:Double-blind placebo-controlled study of the novel therapeutic AEVI-001 in adolescents with ADHD and glutamatergic network gene mutations in children and adolescents with ADHD (SAGA Trial)
Session: Pharmacological treatment of children and adolescents II
Title:Glutamatergic network gene mutations in children and adolescents with ADHD (Phenotype/Genotype Study)
Session: Aetiology II
The posters are available on the Company website at www.aevigenomics.com.
AEVI-001 is an oral non-stimulant pan selective activator/modulator of mGluRs. The molecule has excellent pharmacokinetic and metabolic profiles and crosses the blood brain barrier.
AEVI-001 is an investigational agent that has not been approved by the US FDA or any other regulatory agencies.
About the SAGA Trial
SAGA was a multicenter, dose-optimized trial in adolescents with ADHD. The trial was designed as a randomized, double-blind, placebo-controlled, parallel-group study of AEVI-001 versus placebo in adolescent patients with ADHD who have genetic disorders impacting the mGluR network. The trial enrolled 101 patients (96 evaluable) between the ages of 12-17 years old. The primary and secondary endpoints in the trial were the change from baseline in the ADHD-Rating Scale Version 5 (ADHD-RS-5) Total Score and the percentage of subjects who responded as determined by the Clinical Global Impression of Improvement (CGI-I), respectively. Patients were randomized 1:1 to receive either a six-week course of AEVI-001 or placebo, with a one-week follow-up. Patients were enrolled from sites that participated in the recent phenotype/genotype study. More information on the SAGA trial is available at www.ClinicalTrials.gov (Identifier: NCT02777931).
The Company is also progressing its second program, AEVI-002, into clinical development for Severe Pediatric Onset Crohn's Disease.
More information on the Company and pipeline is located on its website www.aevigenomics.com
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1Data on file and Elia, J. et al, Glutamatergic network gene mutations in children and adolescents with ADHD (Phenotype/Genotype Study). Poster presented at: 6th