Pharnext Announces Positive Topline Results from Pivotal Phase 3 Trial of PXT3003 for Treatment of Charcot-Marie-Tooth Type 1A Disease

PLEO-CMT was a pivotal, 15-month, double-blind Phase 3 study that assessed the efficacy and safety of PXT3003 compared to placebo for the treatment of patients with mild to moderate CMT1A. The study evaluated 2 doses of PXT3003, and patients were randomized 1:1:1. The study enrolled 323 patients aged 16 to 65 years in 30 sites across EU, USA and Canada. The primary endpoint was the Overall Neuropathy Limitation Scale (ONLS) measuring patient disability, in agreement with FDA and EMA for this pathology. A reduction of 0.3 point on this scale was determined to be meaningful according to previously described methodology.
 
Characteristics of the three groups were comparable at baseline. For endpoint analysis, there were 87 patients in placebo, 93 patients in lower dose and 55 patients in higher dose arms at baseline. The lower number of patients in the higher dose is due to unexpected formulation/ stability issues. Nevertheless, compelling results were obtained: compared with placebo, a mean reduction of 0.4-point ONLS (95% CI [0.1,0.6], p=0.008)was observed in the higher dose group. A sensitivity analysis demonstrated the consistency of this result across various statistical models. The secondary endpoints confirmed the superiority of the higher dose, in particular the improvement on the 10-meter walk test with a reduction of 0.5 sec (95%CI [0.1,0.9], p=0.016). A linear dose effect was observed. PXT3003 was safe, well tolerated and showed a similar safety profile as seen in the Phase 2 study. 
 
In this study, PXT3003 provided first evidence of a meaningful improvement of CMT1A patients in showing a statistically significant amelioration on the ONLS disability scale (primary endpoint) confirmed by sensitivity analysis and secondary endpoints together with a good safety profile. Based on these results Pharnext intends to file for market approval in the US and EU. The statistical plan and the results have not yet been reviewed by the regulatory bodies.
 
Pharnext initiated a 9-month, open-label, follow-up extension study, PLEO-CMT-FU, in March 2016 that is currently ongoing with patients who completed the PLEO-CMT study. It is designed to confirm the long-term safety and tolerability of PXT3003 with results expected in H2 2019.
 
Pharnext also expects to initiate a Phase 3 trial of PXT3003 in pediatric CMT1A patients in the first half of 2019, based on a Pediatric Investigation Plan (PIP) agreed upon with the EMA. The results of this trial are not needed for market approval for the adult indication.
 
"We are thrilled with the outcome of the trial and with the clearly demonstrated efficacy of PXT3003 in addressing the debilitating disease progression of CMT1A. We look forward to working closely with regulatory agencies to bring this therapy to patients," said Professor Daniel Cohen, MD, PhD, Pharnext's Co-Founder and Chief Executive Officer. "These results validate the broad potential of our PLEOTHERAPY^TMdrug discovery platform in other neurodegenerative and other disorders and, of course, represent a tremendous milestone for Pharnext."
 
"CMT1A is a chronic, severe and debilitating inherited condition affecting about 125,000 people in the USA and EU, and, until now, there has been no prospect of effective pharmacological treatment," said David Cornblath, MD, Professor of Neurology, Johns Hopkins University, Baltimore, Maryland. "In this trial, PXT3003 demonstrated a significant improvement in patients with mild-to-moderate CMT1A and provided encouraging results that indicate PXT3003 may change the treatment paradigm for the disease. As a clinician, I am excited about the therapeutic potential of PXT3003 and what it means for CMT1A patients and their families."
 
"This is the first large multi-center trial that has demonstrated a positive effect in CMT," said Richard Lewis, MD, Professor of Neurology, Cedars-Sinai Medical Center, Los Angeles, California. "I am delighted that this safe and novel approach may be available to patients with CMT1A."
 
"These results are the first direct translation of a preclinical treatment developed in animal models to CMT1A patients," said Michael Sereda, MD, Professor of Neurology at the Max-Planck Institute of Experimental Medicine, Göttingen, Germany. "I am impressed by the consistency of the therapeutic effect in both preclinical and clinical trials. Data derived from CMT rat models give us important insight regarding the effect of PXT3003 on the diseased peripheral nervous system in CMT1A."
 
Pharnext would like to express its gratitude to the investigators and their teams and to the patients and their families for their commitment to this trial.