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|Aevi Genomic Medicine Provides Top-line Results from the SAGA Trial of AEVI-001|
AEVI-001 represents a novel paradigm of genomic diagnosis and treatment in neuropsychiatric disorders. The mGluR predictive biomarker enabled study of AEVI-001 in an adolescent ADHD sub-population with genetic mutations that disrupt the mGluR network and result in glutamate imbalance.
Although AEVI-001 did not meet the primary endpoint of reduction on the ADHD rating scale (ADHD-RS) compared to placebo, there was an encouraging improvement observed on the inattention subscale (p=0.0515). Additionally, in a pre-specified responder analysis of ADHD-RS improvement of 30% or more, AEVI-001 demonstrated a statistically significant and clinically meaningful improvement compared to placebo. 70% of patients treated with AEVI-001 met this response definition versus 42% on placebo (p=0.0067).
In a second pre-specified responder analysis of Clinical Global Impression of Improvement scale (CGI-I), a key secondary endpoint, AEVI-001 demonstrated a statistically significant and clinically meaningful improvement compared to placebo. 57% of patients treated with AEVI-001 achieved a score of much improved or very much improved compared to 33% on placebo (p=0.0155).
The safety analysis demonstrated that AEVI-001 was well tolerated at all doses. The majority of adverse events were generally mild to moderate in severity and there were no serious adverse events.
"While we are disappointed that the SAGA trial did not achieve statistical significance on the primary endpoint of improvement on ADHD-RS, we are very encouraged by the clinically and statistically significant results we achieved on the ADHD-RS and CGI-I responder analyses," said
We remain committed to this program and our genomic approach, as we believe this is an important drug for patients with neuropsychiatric disorders. Moving forward we plan to explore higher doses, a refined genomic biomarker, and study pediatric patients which should enhance the response rates and effect size of AEVI-001. We look forward to discussing these results with the
"More than 20% of patients with ADHD have an mGluR mutation and current therapies unfortunately do not meet the significant needs of all patients" said
Conference Call Details
Aevi Genomics will host a conference call today to discuss the results of the SAGA trial on
In order to participate in the conference call, please dial 1-866-777-2509 (domestic) or 1-412-317-5413 (international).
The live webcast can be accessed under "Events" in the Investors section of the Company's website at www.aevigenomics.com or you may use the link: https://services.choruscall.com/links/gnmx170321.html
A replay of the call will be available two hours after the end of the conference on
The archived webcast will be available for 90 days in the Investor section of
We encourage participants to pre-register for the conference call using the following link. Callers who pre-register will be given a conference passcode and unique PIN to gain immediate access to the call and bypass the live operator. Participants may pre-register at any time, including up to and after the call start time.
To pre-register, go to: http://dpregister.com/10103458
About the SAGA Trial
The purpose of this multicenter, dose-optimized trial in adolescents with ADHD was to confirm the results from the Phase 1b GREAT study. 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).
AEVI-001 is an investigational agent that has not been approved by the U.S.
AEVI-001 is an oral non-stimulant pan selective activator/modulator of mGluRs. The molecule has excellent PK and metabolic profiles and crosses the blood brain barrier. In the Phase 1b GREAT trial, AEVI-001 demonstrated a strong efficacy signal in CGI-I and
The Company is exploring lifecycle opportunities for AEVI-001 for the treatment of patients with autism spectrum disorder (ASD) and pediatric generalize anxiety disorder (PGAD). In the US in 2012, 1 in 68 children were diagnosed with ASD (2012) increasing from 1 in 150 (2000)8. There is a high unmet need for pharmaceutical treatments for ASD as currently approved medications are indicated for symptoms of irritability in ASD patients. Approximately 17% of the ASD population is mGluR+ patients9. Approximately 3% of US children (3-17 years) have a current diagnosis of anxiety10. There is similar unmet treatment need due to limited pharmacotherapy options. Approximately 13% of pediatric anxiety patients are mGluR+ patients9.
DSM-V defines ADHD as a persistent pattern of inattention and/or hyperactivity-impulsivity that interferes with functioning or development.3 ADHD causes significant impairment in childhood and throughout the lifespan4, as well as increased mortality and psychosocial adversity5. There is no definitive management for ADHD; current management frequently includes a combination of educational support, behavioral interventions, and pharmacotherapy. Current standard of care is the stimulant class of medications including immediate- and extended-release methylphenidate and amphetamine; these products represent 90% of sales in the U.S. ADHD market6. In 2016, U.S. ADHD pharmaceutical product sales were
About the ADHD-RS-5 and CGI-I Scale
The ADHD-RS-5 is a parent reported/clinician-rated scale that was developed to measure the behaviors of children with ADHD, with separate forms for children (ages 5-10 years) and adolescents (11-17 years). The scale consists of 18 items designed to reflect the symptomatology of ADHD based on the Diagnostic and Statistics Manual of Mental Disorders, Fifth Edition (DSM-5) criteria.
Two scales are used to capture the clinician's global assessment. The CGI-I is an assessment of improvement in symptoms, relative to baseline and is based on reports from parents, subjects, and minimal direct observation. Scoring ranges from 1 (very much improved) to 7 (very much worse). The CGI-S scale is used to rate the severity of a subject's condition on a 7-point scale ranging from 1 (Normal, not at all ill) to 7 (Among the most extremely ill subjects).
In addition to the AEVI-001 programs, we are also progressing our second program, AEVI-002 into clinical development for Severe Pediatric Onset Crohn's Disease.
More information on the company and pipeline is located on our website www.aevigenomics.com
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