Pharnext Announces Enrollment of the First Patient in the Open-Label Extension of the Pivotal Phase III Study of PXT3003 in Charcot-Marie-Tooth Disease Type 1A, the PREMIER Trial

Pharnext Announces Enrollment of the First Patient in the Open-Label Extension of the Pivotal Phase III Study of PXT3003 in Charcot-Marie-Tooth Disease Type 1A, the PREMIER Trial

PARIS, France, September 12, 2022 at 8:30 a.m. (CET) – Pharnext SA (FR0011191287 – ALPHA) (” the society “), A late-stage biopharmaceutical company developing novel therapies for neurodegenerative diseases with no satisfactory therapeutic solution, today announces the enrollment of the first patient in the open-label extension study of the PREMIER trial (‘PREMIER-OLE’ – Open Label Extension) of PXT3003 for the treatment of Charcot-Marie-Tooth disease type 1A (CMT1A) in the United States. This patient, who completed the double-blind, placebo-controlled PREMIER study, was enrolled in May 2021. All patients who completed the PREMIER trial will be eligible for inclusion in the PREMIER-OLE study and will receive the dose (DE) of PXT3003 until its commercial availability, if it is finally approved in the United States by the FDA and in Europe by the EMA. PXT3003 is the Company’s most advanced program for the treatment of CMT1A, a disabling disease for which there is currently no approved therapy.

The PREMIER trial, which recently completed recruitment with a total of 387 patients included, is a pivotal international Phase III, randomized, double-blind, placebo-controlled (two arms) study whose primary objective is to to evaluate the efficacy and safety of PXT3003 over a period of 15 months in patients with mild to moderate CMT1A. The dose of PXT3003 tested in the PREMIER study corresponds to the ED tested in the previous Phase III clinical study (the PLEOCMT trial) and in the ongoing open-label Phase III extension study (the PLEOCMT trial -FU). In agreement with regulatory agencies, the primary efficacy endpoint will be the ONLS scale (Overall Neuropathy Limitation Scale) which measures functional motor disability.

Recent data from the ongoing PLEOCMT-FU trial (open-label follow-up study and extension of the first Phase III study, the PLEOCMT trial), announced in May 2022, showed a good safety profile and continuity of the effect of PXT3003 measured on ONLS after a total treatment duration of 5 years. 123 patients with mild to moderate CMT1A are still on treatment with PXT3003 at DE in the PLEOCMT-FU trial.

Dr. Burkhard Blank, Chief Medical Officer of Pharnext, commented : “ The decision to conduct a second open-label extension study, after the PREMIER trial, was prompted by encouraging data from our first open-label extension study of the first Phase III of PXT3003, an ongoing study, which has showed durable benefit of high dose PXT3003 in CMT1A patients after a total treatment duration of 5 years. We look forward to generating additional long-term data to confirm the potential safety and efficacy of PXT3003 in these patients who currently have no treatment options.. »

Xavier Paoli, COO of Pharnext, commented : “ The PREMIER-OLE Study Offers Patients Who Completed Our Second Pivotal Phase III Trial the Opportunity to Continue to Receive Treatment – Each with High-Dose PXT3003 – for This Disabling and Progressive Disease . We are committed to ensuring that these patients with CMT1A have continued access to PXT3003, until its potential marketing authorization and then its commercialization.. »

About Charcot-Marie-Tooth disease type 1A (CMT1A)

Charcot-Marie-Tooth (CMT) diseases include a heterogeneous set of peripheral, hereditary, severe, disabling, progressive and chronic neuropathies. CMT1A, the most frequent subtype of CMT, is an orphan disease with a prevalence of 1/5000 affecting around 150,000 people in Europe and the United States, and around 1,500,000 people worldwide. The genetic mutation causing CMT1A is a duplication of the PMP22 gene coding for a peripheral myelin protein. Duplication of this gene induces overexpression of the PMP22 protein and the inability of Schwann cells to produce normal myelin (neural sheath). The myelin sheath thus degraded (structure and functionality) disrupts the conduction of nerve impulses at the level of the peripheral nerves and causes the degradation of the axons. Because of this deterioration of the peripheral nerves, patients suffer from progressive muscular atrophy in the legs and arms leading to problems with walking, running and balance, as well as functional disorders of the hands. They may also suffer from mild to moderate sensory disturbances. The first symptoms usually appear in adolescence and evolve gradually throughout the patient’s life. In the most severe cases, CMT1A patients become dependent on a wheelchair (at least 5% of cases). To date, no curative or symptomatic drug has received marketing authorization for CMT1A. The management of the disease is limited to supportive care such as orthoses, splints, physiotherapy, occupational therapy or surgery.

More information on https://pharnext.com/fr/disease/charcot-marie-tooth.

About PXT3003

PXT3003 is a new synergistic fixed-dose combination of baclofen, naltrexone and sorbitol formulated as an oral solution administered twice daily. The three components of PXT3003 have been selected to inhibit the overexpression of the PMP22 protein, and thus improve the conduction of nerve impulses from damaged peripheral nerves, a major element in the physiopathology of CMT1A. PXT3003 could also have a positive effect on other motor unit cell types such as the axon (direct protection), neuromuscular junctions or muscle cells. PXT3003 has shown promising and consistent results in Phase II and Phase III preclinical and clinical studies (PLEO-CMT and PLEO-CMT-FU). More information on https://pharnext.com/fr/pipeline/pxt3003.

About the PREMIER Clinical Study

The PREMIER trial is a pivotal Phase III, international, randomized, double-blind, placebo-controlled (two arms) clinical study evaluating the efficacy and safety of PXT3003 in patients with mild to moderate CMT1A over a period of of 15 months. The dose of PXT3003 studied in the PREMIER trial corresponds to the high dose tested in the previous Phase III clinical study (PLEO-CMT). In agreement with regulatory agencies, the primary efficacy endpoint will be the ONLS scale (Overall Neuropathy Limitation Scale) which measures functional motor disability. Secondary evaluation criteria will include the following evaluations: 1) 10 meter walk test (10mWT), 2) Quantification of muscle strength (bilateral assessment of plantar dorsiflexion with a dynamometer), 3) Patient assessment of disease severity using the PGI-S scale (Patient Global Impression of Severity), 4) Patient’s evaluation of the change brought about by the treatment by the PGI-C scale (Patient Global Impression of Change), 5) CMTNS-v2 rating scale (Charcot-Marie-Tooth Neuropathy Score version 2) and 6) Quantification of muscular force with a dynamometer at the level of the hands. Safety and tolerability will be monitored throughout the study. More information about the PREMIER trial is available on the ClinicalTrials.gov website (Study ID: NCT04762758) here.

About Pharnext

Pharnext is a late-stage biopharmaceutical company developing novel therapies for neurodegenerative diseases that currently have no satisfactory therapeutic solution. Pharnext has two products in clinical development. PXT3003 has completed an international Phase III trial with first positive results in Charcot-Marie-Tooth disease type 1A (CMT1A) and has orphan drug status in Europe and the United States. A pivotal international Phase III clinical study of PXT3003 in CMT1A, the PREMIER trial, is currently underway. PXT864 has obtained encouraging Phase II results in Alzheimer’s disease and its development will be pursued in partnerships. Pharnext’s two most advanced drug candidates were discovered with the Pleotherapy™ R&D approach. Pharnext draws investors’ attention to the risk factors, particularly the financial ones detailed in its financial reports. More information on https://pharnext.com/fr.

Pharnext is listed on the Euronext Growth market in Paris (ISIN code: FR0011191287).

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