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Abstract Details

Efficacy and safety of PXT3003 in patients with Charcot-Marie-Tooth type 1A (CMT1A): results of PLEO-CMT, an International Pivotal Phase 3 trial
Movement Disorders
Emerging Science Session (-)
001

CMT1A is a rare, inherited, chronic, peripheral neuropathy affecting 1 in 5000 patients. Patients suffer from distal-dominant muscle atrophy compromising gait and activities of daily living, stocking-glove sensory loss, and overall reduced quality of life. To date, no treatment is available to stabilize or reverse the disease. PXT3003 is a novel oral fixed-dose 3 drug combination: baclofen, naltrexone and D-sorbitol targeting multiple disease pathways.

To assess the effect of PXT3003 on disability measured by the mean change from baseline of Overall Neurology Limitations Scale (ONLS) score at month 12 and 15. Effects on the 10-meter Walk Test (10-mWT) constituted one of the secondary efficacy endpoints.

PLEO-CMT is an international, multi-center, randomized, double-blind, placebo (Pb)-controlled pivotal phase III trial, assessing the efficacy and safety of 2 doses of PXT3003 given twice daily for up to 15 months to mild-to-moderate severity, genetically confirmed, CMT1A patients aged 16 to 65, with Dose 1 (D1) (3 mg baclofen, 0.35 mg naltrexone and 105 mg sorbitol). and Dose 2 (D2) at twice D1.

323 patients were randomized 1:1:1 in the study (D1=109, D2=113, Pb=101). Characteristics of the three groups were comparable at baseline. PXT3003 D2 met the primary endpoint: a clinically meaningful reduction of 0.37-point ONLS (95% CI [0.1,0.64], p=0.008) was observed vs. Pb. In addition, in group D2 a trend for improvement was observed vs. baseline at -0.20-point ONLS (95% CI [-0.447, -0.039], p=0.098). A reduction of 0.47 sec (95%CI [0.09,0.85], p=0.016) was observed on the 10-mWT with D2 vs. Pb. The rate of treatment-emergent adverse events leading to treatment withdrawal was low and similar between groups (D2=5.3%, D1=5.5%, Pb=5.6%).

PXT3003 is the first treatment for CMT1A demonstrated to be effective, safe and well tolerated.

Authors/Disclosures
Florian P. Thomas, MD, PhD, MA, FAAN (Hackensack Meridian Health)
PRESENTER
Dr. Thomas has received personal compensation for serving as an employee of Hackensack Meridian Health. Dr. Thomas has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Pharnext. Dr. Thomas has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Journal of Spinal Cord Medicine. Dr. Thomas has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Gravel & Shae. The institution of Dr. Thomas has received research support from University of Pennsylavania. Dr. Thomas has a non-compensated relationship as a Board Member, Metro New Jersey with National MS Society that is relevant to AAN interests or activities. Dr. Thomas has a non-compensated relationship as a Board Member with American Paraplegia Society that is relevant to AAN interests or activities.
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Daniel H. Cohen, MD, PhD No disclosure on file