- New data from the ongoing Open-Label Phase III Extension Study of PXT3003, the PLEO-CMT-FU trial, suggest good safety profile and continuous treatment effect of PXT3003 measured on the Overall Neuropathy Limitation Scale after 5 years of total trial time
- 126 patients with mild-to-moderate Charcot-Marie-Tooth Disease Type 1A are still on treatment with PXT3003 High Dose in the PLEO-CMT-FU trial
In
Key features of the data analysis are as follows:
- PXT3003 continues to show a good tolerability and safety profile over the course of the first Phase III program (double-blind + ongoing open-label).
- PXT3003 continues to show encouraging efficacy results as measured on the Overall Neuropathy Limitations Scale (‘ONLS’) which evaluates the patient’s functional motor disability.
- The best efficacy signal was observed in the cohort of patients treated with PXT3003 HD during 5 years of total trial time (double blind + ongoing open-label).
- Patients treated with placebo declined on ONLS during the double-blind phase but then improved when switched to PXT3003 in the ongoing open-label phase.
Please refer to the illustration of the ONLS data below for more details.
Dr.
Results of First Double-Blind Phase III (PLEO-CMT) & Open-Label Extension (PLEO-CMT-FU)
Studies of PXT3003 with an ONLS Data Readout at 60 Months of Total Trial Time*
*Results based on database extraction done on
a Cohort of CMT1A patients treated with PXT3003 High Dose during PLEO-CMT and ongoing PLEO-CMT-FU trials
b Cohort of CMT1A patients treated with PXT3003 Low Dose during PLEO-CMT + PLEO-CMT-FU Period 1, and then switched to PXT3003 High Dose during PLEO-CMT-FU period 2
c Cohort of CMT1A patients treated with placebo during PLEO-CMT, PXT3003 Low Dose or High Dose during PLEO-CMT-FU Period 1 and PXT3003 High Dose during PLEO-CMT-FU Period 2
Please refer to a graphic illustration of the first double-blind Phase III (PLEO-CMT) and open-label extension (PLEO-CMT-FU) studies design in the “About the PLEO-CMT-FU Trial” section below.
About the PLEO-CMT Trial
The PLEO-CMT trial was an international, randomized, double-blind, placebo-controlled, Phase III study evaluating the efficacy and safety of PXT3003 in patients with CMT1A, over a 15-month period. Two dose levels, named low dose (‘LD’) and high dose (‘HD’), of PXT3003 in comparison to placebo were tested in patients diagnosed with mild-to-moderate CMT1A (HD equals double LD). A total of 323 patients were enrolled in 29 centers across
About the PLEO-CMT-FU Trial
All randomized CMT1A patients who completed the PLEO-CMT trial (treated with PXT3003 or placebo) were eligible to pursue treatment with PXT3003 in the PLEO-CMT-FU trial. This trial enrolled a total of 187 patients and was designed to primarily assess the long-term safety and tolerability of PXT3003. It was initially planned to be a double-blind, nine-month, Phase III follow-up extension study where patients treated with PXT3003 in the PLEO-CMT trial were eligible to continue their treatment at the same dose (High dose ‘HD’ or Low Dose ‘LD’). Patients treated with placebo in the PLEO-CMT trial were randomized in PLEO-CMT-FU to receive LD or HD of PXT3003. Due to the PXT3003 HD formulation issue which occurred during the PLEO-CMT trial, the HD arm was discontinued in
- Period 1 (9-month treatment period) from
March 2017 toApril 2019 . Patients randomized to PXT3003 LD in PLEO-CMT continued on the same dose. Patients randomized to PXT3003 HD in PLEO-CMT continued on the same dose, but it was given as twice the volume of PXT3003 LD formulation after the PXT3003 HD formulation issue. Patients randomized to placebo in PLEO-CMT continued only on PXT3003 LD after the HD formulation issue. - Period 2 from
July 2018 (still on-going). The 153 patients who entered in PLEO-CMT-FU Period 2 were all switched to PXT3003 HD given as twice the volume of PXT3003 LD formulation.
In PLEO-CMT-FU, on top of safety and tolerability of PXT3003 which is evaluated every 3 months, long-term efficacy is evaluated with the Overall Neuropathy Limitations Scale (‘ONLS’) measured every 6 months. Results from the PLEO-CMT-FU trial will be reported on a yearly basis.
Further information on the PLEO-CMT-FU trial can be found on the ClinicalTrials.gov website (study identification number: NCT03023540) here.
Design of First Double-Blind Phase III (PLEO-CMT) and
Open-Label Extension (PLEO-CMT-FU) Studies of PXT3003
About the PREMIER Trial
The PREMIER trial is an international, randomized, double-blind, two-arm placebo-controlled, pivotal Phase III study, evaluating the efficacy and safety of PXT3003 versus placebo in mild-to-moderate CMT1A patients, over a 15-month period. The dose of PXT3003 tested in the PREMIER trial corresponds to the high dose (‘HD’) tested in the prior Phase III trial (‘PLEO-CMT’). As agreed with regulatory agencies, the primary efficacy endpoint will be the Overall Neuropathy Limitations Scale (‘ONLS’) which measures functional motor disability. The secondary endpoints include the following outcome measures: 1) 10-Meter Walk Test (‘10mWT’), 2) Quantified Muscular Testing (bilateral foot dorsiflexion dynamometry), 3) Patient Global Impression of Severity (‘PGI-S’), 4) Patient Global Impression of Change (‘PGI-C’), 5) Charcot-Marie-Tooth Neuropathy Score, version 2 (‘CMTNS-v2’), and 6) Quantified Muscular Testing (hand grip). Safety and tolerability will be monitored throughout the study. Further information on the PREMIER trial can be found on the ClinicalTrials.gov website (study identification number: NCT04762758) here.
About Charcot-Marie-Tooth Disease Type 1A (‘CMT1A’)
Charcot-Marie-Tooth (‘CMT’) disease encompasses a heterogeneous group of inherited, severe, debilitating, progressive and chronic peripheral neuropathies. CMT1A, the most common type of CMT, is an orphan disease with a prevalence of 1/5000 people affecting about 150,000 people in
About PXT3003
PXT3003 is a novel fixed-dose synergistic combination of baclofen, naltrexone and sorbitol formulated as an oral solution given twice a day. The three individual components of PXT3003 were selected to downregulate the overexpression of PMP22 protein, leading to improvement of neuronal signaling in dysfunctional peripheral nerves that are an essential part of the pathophysiology of this disease. PXT3003 could also have a positive effect on other cellular types of the motor unit such as the axon (direct protection), neuromuscular junctions or muscle cells. PXT3003 has shown promising and consistent results across preclinical and clinical studies in Phase II and Phase III (PLEO-CMT and PLEO-CMT-FU). More information can be found at https://pharnext.com/en/pipeline/pxt3003
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