Aevi Genomic Medicine said today that its lead candidate AEVI-001 has failed the Phase II SAGA trial assessing the treatment in adolescents with metabotropic glutamate receptor mutation-positive (mGluR+) attention/deficit hyperactivity disorder (ADHD).
AEVI-001 missed its primary endpoint of reduction on the ADHD Rating Scale (ADHD-RS) compared to placebo. However, the company said the candidate showed improvement at the highest dose of 400 mg b.i.d., and added that 70% of patients randomized to AEVI-001 in a prespecified responder analysis of ADHD-RS improvement of 30% or more showed statistically significant and clinically meaningful inattention subscale improvement, compared with 42% of placebo patients.
And in what Aevi called a key secondary endpoint, a second prespecified responder analysis of Clinical Global Impression of Improvement scale (CGI-I), 57% of patients treated with AEVI-001 achieved a score of much improved or very much improved compared to 33% on placebo—a statistically significant and clinically meaningful improvement, according to the company.
“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," Aevi CSO Garry Neil, M.D., said in a statement. “We remain committed to this program and our genomic approach, as we believe this is an important drug for patients with neuropsychiatric disorders.”
Aevi plans to explore higher doses and a refined genomic biomarker, as well as study pediatric patients—plans that the company said should enhance the response rates and effect size of AEVI-001.
“We look forward to discussing these results with the FDA and presenting the full data at the World Congress on ADHD in April,” Dr. Neil added.
The mGluR predictive biomarker enabled study of AEVI-001 in an adolescent ADHD subpopulation with genetic mutations that disrupt the mGluR network and result in glutamate imbalance, according to Aevi.
A safety analysis demonstrated that AEVI-001 was well tolerated at all doses. Most adverse events were generally mild to moderate in severity and there were no serious adverse events, the company added.