Update on Phase III trial programme evaluating PXT 3003 forCharcot-Marie-Tooth type 1A disease.-Pharnext S.A.
Pharnext S.A. announced an update from its ongoing Phase III clinical program (PLEO-CMT and PLEO-CMT-FU studies) evaluating PXT 3003 (baclofen + naltrexone hydrochloride+ D-sorbitol) for the treatment of Charcot-Marie-Tooth type 1A disease (CMT1A) in adults. Top-line results from the pivotal PLEO-CMT study are now expected by October 2018. PXT 3003 has already demonstrated safety and tolerability, and the highest dose showed consistent evidence of improvement beyond disease stabilization in CMT1A in the Phase II trial where efficacy was assessed using both the Charcot-Marie-Tooth Neuropathy Score (CMTNS) and the Overall Neuropathy Limitations Scale (ONLS) as main endpoints.
PXT 3003 is currently being evaluated in a pivotal, multi-center, randomized, 15-month, double-blind, placebo-controlled Phase III clinical study (“PLEO-CMT”). The trial was initiated in December 2015 and has enrolled patients aged 16 and older with mild-to-moderate CMT1A in 30 sites across Europe, the U.S. and Canada. The primary endpoint is the change in ONLS score at 12 and 15 months of treatment. Additional outcome measures are being assessed including functional and electrophysiological endpoints. Patients who had completed the Phase III PLEO-CMT trial have been enrolled in a multi-center, 9-month, Phase III follow-up extension study (“PLEO-CMT-FU”) initiated in March 2016. The study was designed to assess the long-term safety and tolerability of PXT 3003 . Following the successful completion of multiple milestones, including a pre-specified evaluation by the independent Data Safety Monitoring Board in September 2017, a blind variability analysis in November 2017 and a futility analysis in November 2017, Pharnext now expects to announce top-line results from the pivotal PLEO-CMT study by October 2018.
Comment:Charcot-Marie-Tooth (CMT) disease encompasses a heterogeneous group of inherited, progressive, chronic peripheral neuropathies. CMT type 1A (CMT 1A), the most common type of CMT, is an orphan disease affecting at least 125,000 people in Europe and the U.S. The genetic mutation responsible for CMT 1A is a duplication of the PMP 22 gene coding for a peripheral myelin protein. Overexpression of this gene causes degradation of the neuronal sheath (myelin) responsible for nerve dysfunction, followed by loss of nerve conduction. As a result of peripheral nerve degradation, patients suffer from progressive muscle atrophy of legs and arms causing walking, running, balance problems and abnormal hand functioning. CMT 1A patients end up in wheelchairs in at least 5% of cases. They might also suffer from mild to moderate sensitive disorders. First symptoms usually appear during adolescence and will progressively evolve through patients' life. 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.