The Charcot-Marie-Tooth Association (CMTA) congratulates CMTA Strategy To Accelerate Research (CMTA-STAR) Alliance Partner Applied Therapeutics on presenting new 24-month results from its Phase III CMT-SORD clinical trial at the 2025 Annual Meeting of the Peripheral Nerve Society (PNS). The findings highlight encouraging signs of sustained clinical benefit and reflect continued momentum in the effort to advance treatments for all forms of CMT.
Govorestat, Applied Therapeutics’ investigational drug, slowed disease progression on MRI, sustained functional and patient-reported gains, and significantly reduced blood sorbitol levels through two years of treatment. The ongoing Phase III INSPIRE trial is evaluating govorestat for the treatment of CMT-SORD, a rare subtype of CMT caused by mutations in the SORD gene.
Statistically significant findings reported by Applied Therapeutics include a correlation between sorbitol reduction and improvement in the CMT-FOM Lower Limb measure, as well as improvement in CMT-Health Index (CMT-HI) scores and correlation with sorbitol percent change. In a preclinical CMT-SORD model, govorestat reduced sorbitol levels in the sciatic nerve by 37 percent. The company reported that govorestat remained safe and well tolerated through 24 months and that a potential FDA new drug application (NDA) submission is expected in 2025.
“We are pleased to see upon examination of the 24-month MRI data that govorestat slowed the progression of the disease versus the MRIs at 12 months, which is an important finding for patients living with this long-term debilitating disease,” said Sue Bruhn, PhD, CMTA CEO. “Seeing these changes on MRI, along with continued clinical benefit, may help open the door not only to a treatment for CMT-SORD, but also to future therapies for other types of CMT.”
Accelerating Research through Collaboration
Discovered in 2020 with CMTA support, the SORD gene mutations that cause CMT-SORD lead to the accumulation of the sugar sorbitol in peripheral nerve cells, where it reaches toxic levels and triggers symptom onset. The higher the sorbitol levels climb, the more severe the symptoms become. This mechanism is unique to CMT-SORD, and there is currently no approved treatment.
This update from our CMTA-STAR Alliance Partner suggests that lowering sorbitol levels may improve symptoms and quality of life for individuals with this form of CMT. These findings also provide a measurable basis for future clinical trials through the use of MRI outcomes. Govorestat has the potential to become the first approved treatment for any form of CMT, and CMTA proudly supports Applied Therapeutics as they move toward a potential new drug application submission with the U.S. Food and Drug Administration.
Published on: May 19, 2025