Applied Therapeutics presented 12, 18, and 24-month results from the INSPIRE Phase 2/3 trial of govorestat for Charcot-Marie-Tooth Sorbitol Dehydrogenase Deficiency (CMT-SORD) at the 2025 Peripheral Nerve Society Annual Meeting. The data suggests govorestat effectively lowers blood sorbitol levels, correlating with improved functional and patient-reported outcomes, including slowed disease progression observed via MRI at 24 months. The company aims for a New Drug Application (NDA) submission in 2025.
This research is particularly crucial given the recent identification of CMT-SORD as a distinct CMT subtype in 2020. The evolving understanding of the disease and the lack of established natural history data present challenges for clinical trial design and outcome measures, as highlighted by the removal of the 10-meter walk-run test from the CMT-Functional Outcome Measure composite during the INSPIRE trial. These positive results offer potential hope for patients with this rare, progressive neuromuscular disease with currently no approved treatments. Demonstrating a therapy’s ability to slow disease progression, especially through objective measures like MRI, is a significant advance that could dramatically alter the treatment landscape for CMT-SORD.
While the primary endpoint of the 10MWRT at 12 months was not statistically significant and later removed from the composite measure, significant correlations were found between sorbitol reduction and improvement in 10MWRT and CMT-FOM Lower Limb domain at 12 months. Improvements in patient-reported outcomes, measured by CMT-HI, were also statistically significant at 12 months and maintained through 24 months. MRI data at 24 months revealed a slowing of disease progression. Importantly, govorestat was generally safe and well-tolerated throughout the study, with 90% of participants continuing into the open-label extension.
These findings strengthen the case for govorestat as a potential treatment for CMT-SORD. The continued positive results from the ongoing open-label extension study, combined with a planned NDA submission in 2025, suggest a promising future for govorestat and offer hope for a much-needed therapy for patients with CMT-SORD. The next steps will be critical, including further analysis of the INSPIRE trial data and interactions with the FDA to determine the optimal regulatory pathway.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
