Drug that targets gut metabolites safe, effective for adolescents with autism

An oral medication that targets metabolites in the gut is both safe and well-tolerated for adolescents with autism spectrum disorder, according to results of a clinical trial published in Nature Medicine.

“As we continue to advance AB-2004 through clinical development, we are excited to share these results which continue to support our previously published scientific research and preclinical data on the role of the gut-brain axis and its impact on neurological conditions,” A. Stewart Campbell, PhD, chief executive officer and head of research and development of Axial Therapeutics, said in a press release related to the study. “We strongly believe that AB-2004 can improve the quality of life of many children with autism.”

Researchers sought to determine the effectiveness of and tolerance for an adsorbent drug that impacts the gut biome in patients diagnosed with ASD.

The phase 1b/2a study was an open-label, single-cohort, multiple-ascending-dose clinical trial that enrolled 30 adolescents from Australia and New Zealand diagnosed with both ASD and gastrointestinal symptoms. Its aim was to determine target engagement of AB-2004 in reducing specific gut-derived microbial metabolites produced by bacteria commonly found in the GI tract, while also exploring initial efficacy endpoints which may guide future clinical development.

Patients were given three daily, weight-adjusted oral doses of AB-2004 totaling 2.25 grams per day, rising to 4.5 grams per day at 2 weeks and 6 grams per day at 4 weeks until the end of treatment at week 8. Follow-up was conducted 4 weeks after the end of treatment. Urine, blood and stool samples were collected, and behavioral assessment performed at baseline, end of treatment and final visit intervals, while overall health was continuously monitored. Twenty-seven of 30 enrolled participants lasted until end of treatment, with one removed due to COVID-19 schedule interruptions. A total of 24 participants remained throughout the duration of the trial.

Results showed a high level of tolerance, with median adherence to the dosing schedule at 97.5%, while no serious adverse events related to the drug or death were recorded for the study’s duration. Negative effects were classified as either mild or moderate and limited to the GI tract, including abdominal pain and nausea.

“The lack of safe and effective treatment options for co-occurring conditions associated with ASD, such as irritability and anxiety, exacerbate the daily challenges faced by children and their families,” Robert L. Hendren, DO, a professor of psychiatry at the Weill Institute for Neurosciences at the University of California, San Francisco, School of Medicine, and a principal investigator for the trial, said in the release.

“A gut-targeted therapeutic approach that safely mitigates the role of bacterial metabolites on traits associated with autism would be an ideal option for addressing the significant unmet treatment need.”

Reference:

Nature Medicine Publishes Full Results from Axial Therapeutics’ Phase 1b/2a Clinical Trial in Autism Spectrum Disorder (ASD): https://www.businesswire.com/news/home/20220211005615/en