Applied Therapeutics Announces Topline Results from the ARISE-HF Phase 3 Study of AT-001 in Diabetic Cardiomyopathy

AT-001 (caficrestat) demonstrated a strong trend in stabilizing cardiac functional capacity, while the placebo group declined over 15 months

AT-001 treatment resulted in a statistically significant difference in cardiac functional capacity in a prespecified subgroup of patients not receiving concomitant treatment with an SGLT2 or GLP-1 (p=0.040) and prevented clinically significant worsening (odds ratio 0.56; p=0.035)

AT-001 demonstrated a favorable safety and tolerability profile

NEW YORK, Jan. 04, 2024 (GLOBE NEWSWIRE) -- Applied Therapeutics, Inc. (Nasdaq: APLT), a clinical-stage biopharmaceutical company developing a pipeline of novel drug candidates against validated molecular targets in indications of high unmet medical need, today announced the topline results of the ARISE-HF Phase 3 trial of AT-001 (caficrestat) in patients with Diabetic Cardiomyopathy (DbCM) at high risk of progression to overt heart failure.  

The primary endpoint of the study was stabilization or improvement in cardiac functional capacity as measured by Peak VO₂ in patients treated with AT-001 1500mg twice daily (BID) as compared to placebo. The placebo-treated group declined by a mean of -0.31 ml/kg/min over 15 months of treatment, while the AT-001 1500mg BID group remained primarily stable, with a mean change of -0.01 ml/kg/min over 15 months. While a trend favored active treatment, the difference between active and placebo treated groups (0.30 ml/kg/min) was not statistically significant (p=0.210).

The ARISE-HF study evaluated the treatment effect of AT-001 as an add-on to diabetes standard of care therapies. Approximately 38% of study subjects were on SGLT2 or GLP-1 therapies for treatment of diabetes, while 62% were not. In a pre-specified subgroup analysis of the primary endpoint in patients not concomitantly treated with SGLT2 or GLP-1 therapies, the placebo group declined by a mean of -0.54 ml/kg/min, while the 1500mg BID AT-001 treated group improved by a mean of 0.08 ml/kg/min over 15 months of treatment, with a difference between groups of 0.62 ml/kg/min (p=0.040). Additionally, in this subgroup analysis, the number of patients who experienced a clinically significant worsening in cardiac functional capacity of 6% or more was substantially higher in the placebo group (46%) as compared to the 1500mg BID AT-001 treated group (32.7%), odds ratio 0.56 (p=0.035). A 6% change in cardiac functional capacity has been shown to predict long-term survival and hospitalization for heart failure. The effect of AT-001 was dose dependent, with the low dose (1000mg BID) demonstrating an intermediate effect between the high dose and placebo.