Diabetic Cardiomyopathy is a specific form of heart failure affecting approximately 20% of patients with Type 2 Diabetes (or 1 in 5 people living with diabetes). There are no treatments approved for DbCM to date, and AT-001 has the potential to be the first therapy approved to treat this devastating disease. DbCM is diagnosed via cardiac echo abnormalities or elevated cardiac biomarkers (via a simple blood test) in the absence of coronary artery disease or uncontrolled hypertension. Patients with DbCM have decreased cardiac functional capacity at the time of diagnosis, leading to early symptoms of disease, which continues to progressively worsen over time, resulting in overt heart failure and death.
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.
The ARISE-HF study is a randomized double-blind placebo-controlled Phase 3 registrational trial. The study has enrolled 675 patients with DbCM at high risk of progression to overt heart failure in the US, EU, UK, Canada, Australia and Hong Kong. The primary endpoint is cardiac functional capacity (as measured by Peak VO2) at 15 months of treatment. Topline data is expected around year-end 2023 or early 2024, and if positive, the company plans to submit for potential regulatory approval. Patients will continue in blinded format for an additional 12 months of treatment (up to 27 months total) to produce secondary endpoint data on progression to overt heart failure, hospitalization, morbidity and mortality, which is not anticipated for regulatory approval, but will support long-term market access. The ARISE-HF trial also includes an embedded sub-study in patients with both DbCM and Diabetic Peripheral Neuropathy evaluating the impact of AT-001 on neuropathy progression.