ARISE-HF Phase 3: AT-001 Study Results in Diabetic Cardiomyopathy

Applied Therapeutics, a biopharmaceutical firm, has reported initial findings from the ARISE-HF Phase 3 trial of AT-001 (caficrestat) in individuals with Diabetic Cardiomyopathy (DbCM) who are at high risk for developing heart failure. The trial aimed to gauge the impact of AT-001 on cardiac functional capacity, comparing it to a placebo. The drug was administered at a dosage of 1500mg twice daily. Over a 15-month period, the placebo group experienced a decrease in cardiac functional capacity, whereas the AT-001 group maintained stability.

Although the overall difference between the treatment and placebo groups was not statistically significant, a subgroup analysis revealed a significant improvement in patients not concurrently on SGLT2 or GLP-1 therapies. In this group, the AT-001 treated patients showed a 0.08 ml/kg/min improvement compared to a 0.54 ml/kg/min decline in the placebo group. The drug also reduced the odds of clinically significant deterioration in cardiac function.

The ARISE-HF study included patients receiving standard diabetes care, with 38% on SGLT2 or GLP-1 therapies and 62% not on these treatments. The impact of AT-001 was dose-dependent, with the higher dose showing a more pronounced effect.

Safety was a key consideration in the study, and AT-001 was found to be safe and well-tolerated. There were no significant differences in serious adverse events between the treatment and placebo groups. The incidence of treatment-related discontinuations was also low.

The full results of the study are set to be presented at a future medical conference, including findings from a sub-study on Diabetic Peripheral Neuropathy.

Riccardo Perfetti, Chief Medical Officer of Applied Therapeutics, highlighted the potential of AT-001 as a valuable tool for treating DbCM, given its safety profile and oral administration. James Januzzi, Principal investigator of the ARISE-HF study, emphasized the importance of stabilizing cardiac functional capacity to prevent progression to heart failure.

Given the positive outcomes, Applied Therapeutics is considering partnering to bring AT-001 to DbCM patients. The company is also focusing on the development of govorestat for the treatment of rare CNS metabolic diseases.

AT-001 is an investigational Aldose Reductase inhibitor currently in Phase 3 trials for DbCM. The drug has been studied in a Phase 1/2 trial involving patients with type 2 diabetes and DbCM.

Applied Therapeutics is committed to developing novel drug candidates for high unmet medical needs, with a pipeline that includes AT-001 for DbCM and AT-003 for Diabetic retinopathy. The company's lead candidate, govorestat, is being developed for CNS rare metabolic diseases.