Benzinga | Dec 16, 2021 07:09AM EST

Applied Therapeutics Announces Initiation Of Registrational Phase 2/3 Study of AT-007 In SORD Deficiency

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 initiation of a registrational phase 2/3 study of AT-007 in Sorbitol Dehydrogenase (SORD) Deficiency. The study, termed INSPIRE (INhibition of Sorbitol Production through Inhibition of the Aldose Reductase Enzyme), will investigate biomarker efficacy, clinical outcomes and safety in people living with SORD Deficiency treated with AT-007 vs. placebo.

Sorbitol Dehydrogenase Deficiency (SORD Deficiency) is a rare, progressive, debilitating hereditary neuropathy that affects peripheral nerves and motor neurons. SORD Deficiency is one of the most common forms of recessive hereditary neuropathy and affects approximately 3,300 patients in the U.S. and 4,000 patients in Europe. The disease is caused by a lack of the enzyme sorbitol dehydrogenase, responsible for metabolism of sorbitol, which causes sorbitol to accumulate at high levels and become toxic to the body. Sorbitol accumulation results in significant disability, loss of sensory function, and neuromuscular dysfunction.

Inhibition of Aldose Reductase addresses the underlying cause of SORD Deficiency by preventing the conversion of glucose into sorbitol, which has been shown to be up to one hundred times higher in the blood of patients with SORD Deficiency compared with unaffected individuals. In a pilot open-label study in 8 SORD Deficiency patients, AT-007 reduced blood sorbitol levels by approximately 66% from baseline through 30 days of treatment. The range of reduction from baseline in patients was 54%-75%. AT-007 was safe and well tolerated in all treated patients.

The global registrational phase 2/3 placebo-controlled trial is designed to evaluate both biomarker efficacy (reduction in sorbitol) and clinical outcomes in patients with SORD Deficiency. The primary biomarker efficacy endpoint will measure reduction in sorbitol at 3 months of treatment compared to baseline. The primary clinical outcome measure will assess changes in Charcot-Marie-Tooth Functional Outcome Measures (CMT-FOM) lower limb function domain, a key measure of mobility and motility in SORD patients, which is greatly impacted by the disease. Key secondary clinical outcomes include CMT-FOM domain sub-scales, CMT Health Index (CMT-HI) patient reported outcomes, fatigue assessment and muscle MRI.

"The INSPIRE registrational trial in SORD Deficiency represents an important milestone for patients and is the second late-stage program initiated with AT-007," said Riccardo Perfetti, MD, PhD, Chief Medical Officer of Applied Therapeutics. "The science demonstrating the role of aldose reductase, and the toxic impact of excess sorbitol, is well-established. We are excited to have achieved proof of concept in the pilot trial and look forward to continuing to advance AT-007 for SORD Deficiency."

"People living with SORD Deficiency are in urgent need of a therapeutic option. The initiation of the first registrational trial in SORD Deficiency marks an important milestone for the patient community," said Amy Gray, CEO of the Charcot-Marie-Tooth Association. "Developing partnerships with companies like Applied Therapeutics is central to the mission of the CMTA and important to the CMT community."

"We look forward to collaborating with Applied Therapeutics and are excited to increase awareness of SORD Deficiency and the potential for a new treatment that could change the course of the disease," said Allison Moore, Founder and CEO of the Hereditary Neuropathy Foundation.

If you or someone you know are interested in qualifying for a free screening for SORD Deficiency, please email: sord@appliedtherapeutics.com