AEVI Genetics completed the parallel phase 2/3 trial on Fasoracetam (AEVI 001) for ADHD and released the results to the 6th World Congress on ADHD.
[b]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)[\b]
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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 Garry A. Neil, M.D., Chief Scientific Officer, Aevi Genomic Medicine. "Based on these new findings, we are validating the prevalence of CNTN4 mutations in ASD and will further characterize the phenotypes associated with this mutation. Importantly, the Company intends to continue the development of AEVI-001 in ADHD and ASD, as well as other potential neuropsychiatric indications in genomically defined populations based on the responder analysis of the SAGA trial."
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.
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Results:
http://phx.corporate...icle&ID=2263475
http://phx.corporate...icle&ID=2255087
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