In the United States (U.S.), approximately 34 million people are living with diabetes – about one in ten people. The hallmark of diabetes is hyperglycemia, or high levels of glucose (sugar) in the blood. In people with diabetes, Aldose Reductase converts glucose to sorbitol, which can cause damage to tissues, including the heart. There are no approved therapies for DbCM, which affects ~17% of people with diabetes representing a prevalence of ~1 in 5 people with diabetes. Approximately 25% of patients with DbCM progress to overt heart failure or death within 18 months of diagnosis.
Applied Therapeutics is committed to advancing research in DbCM and potentially finding a new treatment option for this urgent unmet medical need. Our pipeline candidate AT-001 is an investigational, novel Aldose Reductase Inhibitor currently in a clinical trial 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. AT-001 rapid-release capsules provided sorbitol normalization effects through 10-12hrs post-dose at >10mg/kg. This included protection from food-related sorbitol spikes during times of post-prandial hyperglycemia. Additionally, approximately 50% of AT-001 treated patients demonstrated a clinically meaningful reduction in NT-proBNP, a biomarker of cardiac stress, over 28 days.