Applied Therapeutics' Diabetes-Associated Heart Disease Drug Fails In Phase 3 Study, Stock Plunges

Applied Therapeutics Inc APLT released 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 study's primary endpoint was stabilization or improvement in cardiac functional capacity as measured by Peak VO2 in patients treated with AT-001 1500mg twice daily (BID) 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 group remained primarily stable, with a mean change of -0.01 ml/kg/min.

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 study evaluated the treatment effect of AT-001 as an add-on to diabetes standard-of-care therapies. 

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, 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.

AT-001 was generally safe and well tolerated, with no substantial differences in serious adverse events between AT-001 treated groups compared to placebo.

Price Action: APLT shares are down 35.20% at $2.46 on the last check Friday.