AT-001

AT-001 is an investigational, novel Aldose Reductase Inhibitor (ARI) being developed as an oral therapy for the treatment of Diabetic Cardiomyopathy (DbCM). Applied Therapeutics initiated a Phase 3 registrational study in DbCM with this potent and selective agent in September 2019.

DbCM is a form of Stage B heart failure (HF), a debilitating and progressive disease. Approximately 17% of patients with diabetes have DbCM, and nearly a quarter progress to overt HF within 18 months. There are no approved therapies for DbCM.

AT-001 was evaluated in a Phase 1/2 clinical trial of patients with type 2 diabetes (T2D). Results confirmed that AT-001 was well tolerated and significantly reduced levels of sorbitol, a key toxic biomarker of Aldose Reductase function, to the same levels as healthy volunteers, indicating complete Aldose Reductase inhibition. Twice daily oral AT-001 normalized sorbitol levels throughout the day. This included protection from food-related sorbitol spikes during times of post-prandial hyperglycemia. Additionally, approximately 50% of AT-001 treated patients demonstrated a significant reduction in NT-proBNP, a biomarker of cardiac stress, over 28 days.

AT-001 is also being investigated for Diabetic Peripheral Neuropathy in a sub-study of the DbCM Phase 3 program.

Edit

1.       Lam, 2015: https://pubmed.ncbi.nlm.nih.gov/25908570/

2.       Dandamundi et al., 2014: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076144/