Pharnext Announces Positive Topline Results
from Pivotal Phase 3 Trial of PXT3003
for Treatment of Charcot-Marie-Tooth Type 1A Disease
• Higher dose met primary endpoint, the Overall Neuropathy Limitation Scale (ONLS), with statistical
significance (p = 0.008)
• Higher dose met secondary endpoint, the 10-meter walk test, with statistical significance (p=0.016)
• Safe and well tolerated, no treatment related serious adverse event reported in the higher dose group
• Based on these positive results, Pharnext intends to file for market approval in the US and Europe
• Conference callstoday at 11:30 am EDT / 5:30 pm CET in French and 1:00 pm EDT / 7:00 pm CET in English
PARIS, France, 7:30 am (CET), October 16, 2018 – Pharnext SA (FR0011191287 - ALPHA), a biopharmaceutical
company pioneering a new approach to the development of innovative drug combinations based on big data
genomics and artificial intelligence, today announced positive topline results from its pivotal Phase 3 clinical
trial (PLEO-CMT) evaluating two doses of PXT3003 compared to placebo during 15 months for the treatment
of Charcot-Marie-Tooth type 1A disease (CMT1A).
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 two 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.
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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
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to file for market approval in the US and EU. The statistical plan and the results have not yet been reviewed by
the regulatory authorities.
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 PLEOTHERAPYTM drug 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.