Applied Therapeutics, Inc. (Nasdaq: APLT) is thrilled to announce encouraging sorbitol reduction results from their ongoing global Phase 3 INSPIRE trial. The trial is evaluating the effect of AT-007, a once-daily oral medication, on 50 patients aged 16-55 suffering from SORD Deficiency. This debilitating hereditary axonal neuropathy, caused by mutations in the Sorbitol Dehydrogenase gene, is characterized by an inability to metabolize the sugar sorbitol, resulting in accumulation of toxic levels and motor neuron degeneration. AT-007 acts as a central nervous system penetrant Aldose Reductase Inhibitor, blocking conversion of glucose to sorbitol and, thus far, showing promise in reducing toxic levels in SORD patients.
The Phase 3 INSPIRE trial has exciting news: AT-007 has drastically reduced sorbitol levels in patients with SORD Deficiency by an average of 52% (or 16,000ng/ml) in just 90 days of treatment. This astounding result was statistically significant compared to placebo (p<0.001).
The INSPIRE trial revealed that, at baseline, the mean blood sorbitol level for SORD patients was about 29,000ng/ml, ranging from 22,000ng/ml to 38,000ng/ml. This study went on to demonstrate a statistically significant correlation between sorbitol level and key clinical outcome measures, such as 10-meter-walk/run speed, 4-stair climb speed and sit-to-stand test. When taken into consideration with the biology of the disease and supportive animal model data, the Company believes there is strong evidence that reducing sorbitol levels is likely to improve patient outcomes. Therefore, the Company is working with the FDA to determine the best regulatory path forward and data needed for an NDA submission, in order to bring a safe and effective treatment to SORD Deficiency patients as quickly as possible.
The INSPIRE study is continuing in a blinded format to assess clinical outcomes at 12 months. If the primary clinical outcome measure, the 10-meter-walk/run, reaches statistical significance, the study will be completed and unblinded. If not, the study will continue to 24 months for a final statistical analysis. So far, AT-007 has shown to be safe and well-tolerated.
The results of our interim sorbitol analysis are extremely encouraging. Our findings suggest that AT-007 has the potential to effectively reduce sorbitol levels in a clinically meaningful way. According to Riccardo Perfetti, MD, PhD, Chief Medical Officer of Applied Therapeutics, these results could have a significant impact on patient outcomes.
The role of sorbitol in SORD Deficiency is undeniable, but AT-007 is promising in its ability to reduce the sorbitol levels seen in patients. According to Michael Shy, MD, the Director of the Division of Neuromuscular Medicine at Carver College of Medicine, University of Iowa Medical Center and Principal Investigator on the INSPIRE Phase 3 trial, the reduction in sorbitol level seen thus far with AT-007 is impressive and could mean improved clinical outcomes for patients.
The Charcot-Marie-Tooth Association is thrilled at the new data from Applied Therapeutics regarding SORD Deficiency. According to CEO Amy Gray, the organization is committed to ensuring that those suffering from the debilitating disease have access to a safe and effective treatment. They are continuing to work closely with Applied Therapeutics and the patient community to ensure that their needs are met.
The Hereditary Neuropathy Foundation is dedicated to providing hope and support to those affected by SORD Deficiency, a devastating degenerative disease without any known treatments. Working closely with Applied Therapeutics, the FDA and the patient community, the Foundation is committed to making treatments available as soon as possible in order to bring much-needed relief to those suffering from this disorder and other hereditary neuropathies.
The Company invites you to join their conference call today at 8:30am Eastern to learn more about their results and discuss their progress!
About AT-007
AT-007 is an Aldose Reductase inhibitor that has been clinically proven to be a CNS penetrant, and is currently being studied as a potential treatment for a number of rare neurological diseases including Galactosemia, SORD Deficiency and PMM2-CDG. In clinical trials, AT-007 has been shown to reduce plasma galactitol levels in both adults and children with Galactosemia. To further investigate its efficacy, AT-007 is being studied in a Phase 3 clinical outcomes trial (ACTION-Galactosemia Kids) in children between the ages of 2-17 and a long-term open-label study in adults with Galactosemia. Additionally, AT-007 has been found to reduce blood sorbitol levels in adults with SORD Deficiency, and is now being studied in a Phase 3 trial (INSPIRE) to assess its biomarker efficacy and clinical outcomes in those 16 and older. So far, the drug has been generally safe and well-tolerated in all trials.
About Applied Therapeutics
Applied Therapeutics is revolutionizing the medical industry with its innovative clinical-stage biopharmaceutical pipeline. The Company is developing novel drug candidates that target molecular validations in order to treat unmet medical needs. AT-007 is Applied Therapeutics’ lead drug candidate and is a novel central nervous system penetrant Aldose Reductase Inhibitor that is being developed to treat rare metabolic diseases such as Galactosemia, SORD Deficiency, and PMM2-CDG. Moreover, AT-001 is a potent ARI being developed to treat the fatal fibrosis of the heart known as Diabetic Cardiomyopathy. Last but not least, AT-003 is an ARI designed to cross through the back of the eye when dosed orally and is being developed to treat Diabetic Retinopathy. Applied Therapeutics is making strides in its mission to provide new and effective treatments for a variety of life-threatening diseases.