Background and objectives:
Charcot-Marie-Tooth (CMT) disease comprises genetically heterogeneous inherited peripheral neuropathies. This retrospective analysis examines trends in CMT clinical research over the past two decades.
Methods:
A search of clinicalTrials.gov identified studies involving drugs, biologicals, devices, or combination products including the terms “Charcot-Marie-Tooth” or “CMT.” Of 312 records, 28 studies with CMT as the primary indication were included and divided into two periods: P1 (2005–2014) and P2 (2015–2024). Differences between the 2 periods were analyzed using descriptive statistics and two-tailed t-tests assuming unequal variances.
Results:
Study numbers increased significantly in P2 (22) vs P1 (6) (↑267%, p<.01). 96% were interventional trials, and 79% evaluated drugs or biologicals, increasing 350% in P2 (18) vs P1 (4) (p<.01). 64% of studies were in adult-only populations, which increased 250% (p<.05), while studies including pediatric populations increased 300% (non-significant). Early-phase (I–II) trials accounted for 57% and increased 333% in P2 (p<.01). There were no significant trends in other development phases or studies with no development phase. 57% of studies included efficacy endpoints as the primary outcome. Efficacy-endpoint trials increased 200% (not significant), while safety-endpoint trials rose 800% (p<.05). Non-industry-funded studies comprised 61%, and increased 116% in P2 (non-significant), whereas industry-funded studies grew 800% (p<.01). Average trial duration increased by 76% in P2 vs P1 (2189 vs 1241 days).
Conclusions:
Clinical research activity in CMT has expanded significantly over the past decade, driven by early-phase studies of drugs and biologicals, primarily in adult populations. Although non-industry groups remain the main sponsors, industry participation has risen sharply in the past decade. However, late-phase development (phase 2b–3) has not yet increased significantly. Longer trial durations and inconsistent outcome measures suggest greater study complexity and highlight ongoing unmet needs. Continued innovation and standardized outcome frameworks are essential to advance therapeutic development for CMT.