Pharnext Announces On-Schedule Completion of Patient Enrollment in its Pivotal Phase III Trial of PXT3003, the PREMIER Trial, for the Treatment of Charcot-Marie-Tooth Disease Type 1A

PARIS, France, May 30 2022, 08:30 am CET – Pharnext SA (FR0011191287 - ALPHA) (the “Company”), an advanced late-clinical stage biopharmaceutical company developing novel therapeutics for neurodegenerative diseases with high unmet medical need, today announces it has completed the enrollment of 387 patients in its pivotal Phase III clinical study of PXT3003, the PREMIER trial, in Charcot-Marie-Tooth disease type 1A (‘CMT1A’). This important company milestone, highlighted in previously announced timelines, has now been completed. PXT3003 is the Company’s lead program to treat CMT1A, a debilitating disease with currently no existing approved therapies.


PREMIER trial is an international, randomized, double-blind, two-arm placebo-controlled, pivotal Phase III study, where the primary objective is to evaluate 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 clinical study, the PLEO-CMT trial, and the ongoing open-label extension Phase III study, the PLEOCMT-FU trial. As agreed with regulatory agencies, the primary efficacy endpoint will be the Overall Neuropathy Limitations Scale (‘ONLS’) which measures functional motor disability. For more information on the PREMIER trial please refer to the “About the PREMIER Trial” paragraph below.

Patient enrollment in the PREMIER trial took place in 52 centers across the US, Canada, Europe and Israel, with the final number of patients randomized exceeding the target of 350 patients defined in the protocol. Top line data are expected to be announced in Q4 2023.


Dr. David Horn Solomon, Chief Executive Officer of Pharnext, commented: “Completing enrollment of the Pivotal Phase III study of PXT3003, the PREMIER trial, represents a significant milestone for Pharnext and we are delighted that the study has completed enrollment on schedule across an international range of trial centers. It brings us one step closer to a potential treatment for those with CMT1A, a debilitating disease which affects around 1.5 million people globally.”


Dr. Burkhard Blank, Chief Medical Officer at Pharnext commented: “We are excited to complete the enrollment of our PREMIER trial in Q2 2022 as planned and look forward to reporting top line data, expected in Q4 2023. We are grateful to the patients and investigators participating in this trial. If approved, PXT3003 has the potential to help transform the lives of those who live with CMT1A.”


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 Europe and the U.S. and about 1,500,000 people worldwide. The genetic mutation responsible for CMT1A is a duplication of the PMP22 gene coding for a peripheral myelin protein. The duplication of this gene results in overexpression of the PMP22 protein and failure of Schwann cells to produce normal myelin (neuronal sheath). The lack of a normal myelin structure and function leads to abnormal peripheral nerve conduction and axonal loss. As a result of peripheral nerve degradation, patients suffer from progressive muscle atrophy in both the legs and arms causing problems with walking, running and balance as well as abnormal hand functioning. They might also suffer from mild to moderate sensory disorders. First symptoms usually appear during adolescence and will progressively evolve throughout life. Patients with the most severe form of CMT1A end up in wheelchairs, representing at least 5% of cases. To date, no curative or symptomatic medications have been approved and treatment consists of supportive care such as orthotics, leg braces, physical and occupational therapy or surgery. More information can be found at https://pharnext.com/en/disease/charcot-marie-tooth.


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.


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 Pharnext
Pharnext is an advanced clinical-stage biopharmaceutical company developing novel therapeutics for neurodegenerative diseases that currently lack curative and/or disease-modifying treatments. Pharnext has two lead products in clinical development. PXT3003 completed an international Phase III trial with positive topline results for the treatment of Charcot-Marie-Tooth disease type 1A (‘CMT1A’) and benefits from orphan drug status in Europe and the United States. An international pivotal Phase III study of PXT3003 in CMT1A, the PREMIER trial, is currently ongoing. PXT864 has generated encouraging Phase II results in Alzheimer’s disease and will be advanced through partnerships. Both of Pharnext’s lead assets originated from the Pleotherapy™ R&D approach. Pharnext draws the attention of investors to the financial and other risk factors detailed in its financial reports. More information can be found at www.pharnext.com.
Pharnext is listed on the Euronext Growth Stock Exchange in Paris (ISIN code: FR0011191287).