Applied Therapeutics, Inc. announced full enrollment in the Phase 3 registrational ARISE-HF trial, studying AT-001, a selective Aldose Reductase inhibitor, in patients with Diabetic Cardiomyopathy (DbCM). The ARISE-HF study is a randomized double-blind placebo-controlled Phase 3 registrational trial. The study 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 VO(2)) 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. AT-001 is a novel, potent, highly selective Aldose Reductase inhibitor. Aldose Reductase is a well validated molecular target, and over-activation of this enzyme is known to result in many diabetic complications, including Diabetic Cardiomyopathy and Diabetic Peripheral Neuropathy.

In the ARISE-HF study, AT-001 is dosed twice daily in oral capsules as an add-on to other Type 2 Diabetes standard of care medications. AT-001 is safe and well tolerated to date, with approximately 80 patients having already completed the primary endpoint at 15 months of treatment in the study. 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.