AEVI-001 fails to meet efficacy endpoint for ADHD

AEVI-001, an oral non-stimulant, did not meet its primary efficacy endpoint for ADHD, but did exhibit an encouraging trend in improvement at its highest dose, according to findings released by Aevi Genomic Medicine.

“More than 20% of patients with ADHD have [a metabotropic glutamate receptors] mutation, and current therapies, unfortunately, do not meet the significant needs of all patients,” study researcher Robert L. Findling, MD, MBA, of Johns Hopkins University School of Medicine, said in a press release. “Although the SAGA trial did not meet its primary endpoint, the clinical results highlight a clear potential to benefit patients. I look forward to working with Aevi Genomics to better understand these results and further develop the molecule.”

To confirm phase 1b study results, researchers conducted a multicenter, dose-optimized trial among 96 adolescents with ADHD and genetic disorders affecting the metabotropic glutamate receptors (mGluR) network. Participants were randomly assigned to receive AEVI-001 or placebo for 6 weeks with a 1-week follow-up.

AEVI-001 did not meet the primary endpoint of reduction on the ADHD rating scale; however, researchers noted improvement on the inattention subscale (P = .0515), compared with placebo.

In a prespecified responder analysis of improvement on ADHD rating scale of 30% or more, AEVI-001 exhibited statistically significant improvement placebo. Seventy percent of participants who received AEVI-001 achieved this response, compared with 42% of those who received placebo (P = .0067).

In a second prespecified responder analysis, 57% of participants who received AEVI-001 achieved a score of much improved or very much improved on the Clinical Global Impression of Improvement scale, compared with 33% of those who received placebo (P = .0155).

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AEVI-001 was well-tolerated at all dosages, according to researchers. 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,” Garry Neil, MD, chief scientific officer at Aevi Genomic Medicine, said in the release. “There is a clear signal of efficacy and clinical benefit with AEVI-001 at the highest dose. The drug demonstrated a dose-response limited by the maximum dose of 400 mg BID and a favorable safety profile. We remain committed to this program and our genomic approach, as we believe this is an important drug for patients with neuropsychiatric disorders.”

Aevi will study higher doses, a more refined genomic biomarker and employ pediatric patients in future studies, according to Neil.