Applied Therapeutics, Inc. announced positive interim 12-month results from the ongoing Phase 3 INSPIRE trial, in which the primary endpoints and several key secondary endpoints were achieved. The INSPIRE trial is a Phase 3 double-blind placebo-controlled registrational study evaluating the effect of once-daily (QD) oral govorestat (AT-007) in 56 patients aged 16-55 with SORD Deficiency in the US and Europe. SORD Deficiency is a debilitating, hereditary axonal neuropathy caused by mutations in the Sorbitol Dehydrogenase gene, leading to an inability to metabolize the sugar sorbitol and resulting in accumulation of high levels of toxic sorbitol, which causes motor neuron degeneration and loss of mobility and motility.

Govorestat is a central nervous system penetrant Aldose Reductase Inhibitor, which blocks the conversion of glucose to sorbitol, and has previously been shown to reduce sorbitol levels in patients with SORD Deficiency. The objective of this pre-specified, 12-month interim analysis was to evaluate early indicators of govorestat treatment effect in order to inform future regulatory discussions and support a potential New Drug Application (NDA) submission, due to the urgent need for treatment and absence of any other options for patients with SORD Deficiency. The 12-month interim analysis was comprised of a clinical efficacy primary endpoint based on correlation of sorbitol with composite clinical outcome measures, and a pharmacodynamic (PD) biomarker primary endpoint based on sorbitol reduction.

Interim Analysis Results: Demonstrated statistically significant correlation between sorbitol level and the prespecified CMT-FOM composite clinical endpoint (10-meter walk-run test, 4 stair climb, sit to stand test,6-minute walk test and dorsiflexion) (p=0.05). Govorestat treatment provided sustained reduction in sorbitol level in patients with SORD Deficiency over 12 months of treatment, which was statistically significant compared to placebo (p<0.001). Govorestat treatment also resulted in a highly statistically significant effect (p=0.01) on the CMT Health Index (CMT-HI), an important patient-reported outcome measure of disease severity and well-being, which was a secondary endpoint in the study.

Aspects of the CMT-HI that demonstrated a treatment effect included lower limb function, mobility, fatigue, pain, sensory function, and upper limb function. Govorestat was safe and well tolerated, with similar incidence of adverse events between active and placebo-treated groups.