First-ever effective treatment of Charcot-Marie-Tooth disease type 1a

PXT3003 is the first treatment for Charcot-Marie-Tooth disease type 1a (CMT1A) that is effective, safe, and well tolerated. This was demonstrated in the pivotal phase 3 trial PLEO-CMT. PXT3003 is a novel oral fixed-dose combination of baclofen, naltrexone, and D-sorbitol, targeting multiple disease pathways.

CMT1A is a rare, inherited, chronic, peripheral neuropathy for which no registered treatment is available to stabilise or reverse it. The PLEO-CMT trial assessed the effect of PXT3003 on disability, measured by the mean change in Overall Neurology Limitations Scale (ONLS) score after 12 and 15 months [1]. The 323 participants were 16-65 years of age and had genetically confirmed CMT1A of mild-to-moderate severity. They were randomised 1:1:1 to Dose 1 (D1: 3 mg baclofen, 0.35 mg naltrexone, and 105 mg sorbitol), Dose 2 (D2: twice D1), or placebo. Characteristics of the groups were comparable at baseline.

PXT3003 D2 met the primary endpoint: there was a 0.37-point reduction of ONLS (P=0.008) vs placebo. Dr Florian Thomas (Hackensack University Medical Center, USA) explained a minimum 0.30-point reduction of ONLS had been deemed clinically meaningful. In addition, in group D2 a trend for improvement was observed compared with baseline at -0.20-point ONLS (P=0.098). Dr Thomas: “This group improved as much as the placebo group deteriorated.” Also with D2, a reduction of 0.47 seconds was observed on the 10-meter walk test, the main secondary endpoint (P=0.016). There were no safety concerns: the rate of treatment-emergent adverse events leading to withdrawal was low and similar between groups (D2=5.3%, D1=5.5%, placebo=5.6%). Dr Thomas said he was not surprised since both D1 and D2 were low.

  1. Thomas FP, et al. Efficacy and safety of PXT3003 in patients with Charcot-Marie-Tooth type 1A (CMT1A): results of PLEO-CMT, an International Pivotal Phase 3 Trial. AAN 2019, Emerging Science 001.