In a statement released on February 15, 2024, by Charcot-Marie-Tooth Association (CMTA) Alliance Partner, Applied Therapeutics, the company said that its INSPIRE Phase III trial for a certain type of Charcot-Marie-Tooth disease (CMT), called SORD-deficiency, showed positive interim 12-month results and that the trial’s primary endpoints, along with several key secondary endpoints, were achieved. The INSPIRE trial is a Phase III double-blind placebo-controlled study evaluating the effect of its drug, govorestat (AT-007), in 56 patients aged 16-55 who have genetically confirmed SORD-deficiency in the US and in Europe.

In its statement, Applied Therapeutics said the trial at its 12-month mark has shown a statistically significant correlation between sorbitol levels and the prespecified CMT Functional Outcomes Measure (CMT-FOM) and that treatment with its drug, govorestat, continued to maintain lower sorbitol levels in CMT-SORD patients over the course of 12 months which is statistically significant compared to the placebo (p<0.001). The company also said that treatment with govorestat 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.

The CMT-HI is a secondary outcome measure in the INSPIRE study, with improvements reported in lower and upper limb function, mobility, fatigue, pain, and sensory function. In addition to patient-reported outcomes measured by the CMT-HI, the company said that the biggest symptom improvements were reported in the 10-meter walk/run test and reductions in foot drop severity. This translates into patients reporting an improvement in quality-of-life and shows improvements in mobility impairments caused by CMT-SORD.

Discovered in 2020 with CMTA support, CMT-SORD, also known as SORD-deficiency, is caused by mutations in the Sorbitol Dehydrogenase gene—the SORD gene. These mutations cause the sugar sorbitol to accumulate in peripheral nerve cells and climb to very high toxic levels, leading to CMT symptom onset. The higher the sorbitol levels climb, the more severe symptoms become. In CMT, this feature is unique to this type, and there is no approved treatment to help these community members.

Today’s news from our alliance partner suggests that lowering sorbitol levels has the potential to improve symptoms and overall quality-of-life for our community members who have this unique type of CMT. The CMTA continues to follow this study with great interest and support our alliance partner as they have announced the intention to discuss a potential new drug application (NDA) submission with the U.S. Food and Drug Administration (FDA) based on the available trial data.

Published: February 15, 2024