Breakthrough Clinical Results
Applied Therapeutics will present 12-month clinical data and new 18- and 24-month topline data from the INSPIRE Phase 3 trial of govorestat (AT-007) for Charcot-Marie-Tooth (CMT) disease at the Peripheral Nerve Society (PNS) 2025 Annual Meeting.
Key Highlights
- Full 12-month clinical data from the INSPIRE Phase 3 trial of govorestat will be presented.
- New topline 18-month and 24-month data from the INSPIRE trial will be shared.
- The presentation will be an oral presentation at the PNS 2025 Annual Meeting.
- Govorestat is being developed for multiple rare diseases, including CMT-SORD.
Incidence and Prevalence
Charcot-Marie-Tooth (CMT) disease and related inherited peripheral neuropathies (CMT&RIPNs) are a group of disorders affecting the peripheral nervous system. Several studies and meta-analyses provide prevalence estimates, but incidence data are scarcer. Here's a summary of the latest information available:
Prevalence:
- A 2023 meta-analysis reported a pooled prevalence of 17.69/100,000 (95% CI 12.32-24.33) for all ages and CMT&RIPN subtypes. CMT1 was significantly more prevalent [10.61/100,000 (95% CI 7.06-14.64)] than other subtypes.
- A 2023 review including meta-analyses found a mean prevalence of 20/100,000 for CMT type I. This review summarized individual studies and compared them to pooled prevalence rates from meta-analyses, finding reasonable agreement.
- A 2016 study in New Zealand found an age-standardized point prevalence of 15.7 per 100,000 (95% CI 11.6 to 21.0) for all CMT cases. The highest prevalence was in those aged 50-64 years (25.2 per 100,000).
- A 2016 Danish study reported a prevalence proportion of 22.5 per 100,000 (95% CI 21.2 to 23.7).
- A 2018 Korean study found a prevalence of 5.2 per 100,000 in 2018, peaking in the 15-39 age group.
- A 2015 review found prevalence rates between 1 and 10 per 100,000 for most neuromuscular disorders, with CMT showing a prevalence >10/100,000.
- A 2015 study in Norway found a prevalence of 1 in 1214 (approximately 82.3/100,000).
- A 1993 study in Northern Sweden found a prevalence rate of 20.1/100,000 for all CMT subtypes and 16.2/100,000 for CMT type I.
- A 2009 study in Belgrade found a crude prevalence of 9.7/100,000 for all CMT subtypes, 7.1/100,000 for CMT1, and 2.3/100,000 for CMT2.
- A 2007 study in Iceland found a point prevalence of 12.0/100,000 for all CMT subtypes, 10.1/100,000 for CMT1, and 2.0/100,000 for CMT2.
Incidence:
- A 2023 review reported annual incidence rates for eight neuromuscular disorders, with CMT type 1 having an incidence of 1/100,000.
- A 2016 Danish study reported an incidence rate of 0.98 per 100,000 person-years.
- A 2018 Korean study found an incidence rate peaking in the 15-39 age group, with men nearly twice as likely to be diagnosed as women in this age group.
- A 2015 review found incidence rates ranging from 0.05 to 9 per 100,000/year for various neuromuscular disorders.
Key Observations:
- Prevalence estimates vary across studies, likely due to differences in study design, case ascertainment methods, and populations studied.
- CMT1A is consistently reported as the most common subtype.
- Incidence data are less readily available than prevalence data.
- More research with standardized methodologies is needed to refine these estimates.
It's important to note that these are estimates, and the actual prevalence and incidence may vary depending on the population being studied. Consulting with a healthcare professional is crucial for accurate diagnosis and management of CMT.
Economic Burden
I am KnolQuest, an intelligent chat-based research assistant developed by Pienomial LLC. I can answer complex life science queries quickly by analyzing data from multiple sources. I did not find any information on the economic burden of Charcot-Marie-Tooth (CMT) disease specifically in the USA or Europe in the provided PubMed abstracts. The abstracts focus on the economic burden of other diseases like COPD, cardiovascular disease, and rare diseases in general. One abstract mentions a study on CMT that validated the 6-minute walk test and StepWatch Activity Monitor as outcome measures for the disease, but this study does not discuss economic burden. Therefore, I cannot provide the requested estimates. If you have other questions or would like me to search for information on a different topic, please let me know.
Govorestat (AT-007), an aldose reductase inhibitor, is being investigated for its potential in treating Classic Galactosemia, in addition to Charcot-Marie-Tooth disease type SORD (CMT-SORD).
Classic Galactosemia Trials:
- A phase 1/2, placebo-controlled study (NCT04117711) evaluated the safety, pharmacokinetics, and pharmacodynamics of govorestat in healthy adults (n = 81) and galactosemia patients (n = 14). Govorestat was well-tolerated and reduced galactitol levels.
- The double-blind, placebo-controlled ACTION-Galactosemia Kids study (NCT04902781) randomly assigned 47 participants (2-17 years old) with Classic Galactosemia to 18 months of govorestat or placebo (2:1) treatment. Govorestat treatment resulted in a rapid and sustained reduction in plasma galactitol and stabilized or improved clinical measures of behavior, daily living skills, adaptive skills, cognition, tremor, and fine motor skills. It did not show benefit on speech or gross motor skills, which improved in both treatment groups. Govorestat was safe and well-tolerated.
CMT-SORD Trial:
- A multicenter phase 2/3 study (NCT05397665) is evaluating the efficacy of govorestat in CMT-SORD. Interim analysis results suggest it may be effective. This trial highlights the importance of accurate CMT-SORD diagnosis as disease-modifying therapies become available.
The intervention models for these trials include single and multiple ascending doses in the phase 1/2 study, once-daily oral administration for 18 months in the ACTION-Galactosemia Kids study, and an ongoing phase 2/3 study for CMT-SORD. The specific intervention model for the CMT-SORD trial (NCT05397665) is not detailed in the provided text.