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Pharnext Announces Pleotherapy Proof of Concept in Charcot-Marie-Tooth Disease Type 1A

by | Dec 19, 2014 | 12 comments

Pharnext Announces Pleotherapy Proof of Concept in Charcot-Marie-Tooth Disease Type 1A through Two Peer-Reviewed Publications                                                       

–  First Paper Shows Consistent and Synergic Preclinical Data for PXT-3003
in Two Different CMT 1A Rodent Models  –
–  Second Paper Presents Positive Phase 2 results of PXT-3003
in 80 Patients with Mild to Moderate CMT 1A  –
– Phase 3 Clinical Trial of PXT-3003 in CMT1A set to begin in 2015 –

PARIS, December 18th, 2014 – Pharnext SAS today announced the proof of concept of its pleotherapy research and development approach based on a proprietary network pharmacology platform that identifies synergic combinations of drugs already approved for other diseases. Indeed, Pharnext’s lead pleodrug, PXT-3003, has shown positive results both in preclinical and Phase 2 clinical studies published today in the Orphanet Journal of Rare Diseases.

In the preclinical publication titled “A combination of three repurposed drugs is active in models of Charcot-Marie-Tooth type 1A neuropathy” by Ilya Chumakov, et al., data shown in two different CMT 1A rodent models that PXT-3003:

  • Inhibited the overexpression of the PMP 22 gene responsible for myelination perturbation in CMT 1A;
  • Improved myelination of peripheral nerves;
  • Improved clinical motor and sensitive impairment.

In the Phase 2 clinical trial publication titled “An exploratory randomised double-blind and placebo-controlled phase 2 study of a combination of Baclofen, Naltrexone and Sorbitol (PXT-3003) in patients with Charcot-Marie-Tooth disease type 1A” by Shahram Attarian, et al., the authors report that PXT-3003:

  • Was safe and well tolerated
  • Showed, beyond stabilization, a significant 14.4% improvement in the ONLS (Overall Neuropathy Limitation Scale) composite score versus placebo. ONLS is considered a major scale to evaluate disability of upper and lower limbs in peripheral neuropathies. FDA has recommended the use of ONLS as a primary efficacy endpoint in CMT disease.
  • Showed a consistent trend of improvement in other clinical and electrophysiological measures including CMTNS (Charcot-Marie-Tooth Neuropathy Score), the six-minute walk test, ankle dorsiflexion, hand grip or the nine-hole peg test.


Catherine Scart-Grès, M.D., chief medical officer of Pharnext, said, “CMT is a rare and progressive hereditary neurological disease with no currently approved or effective treatment available. PXT-3003 was well tolerated and produced a consistent dose effect on most efficacy endpoints. In a disease such as CMT1A that begins in childhood and is progressive, a therapy that can not only stabilize but also improve symptoms can have a profound impact on the course of the disease and patient lives”.

Daniel Cohen, M.D., Ph.D., chairman and chief executive officer of Pharnext, said, “Positive preclinical and Phase 2 data for PXT-3003 validate our pleotherapy approach based on network pharmacology. We look forward to continuing the development of PXT-3003 with an international Phase 3 clinical trial set to begin in 2015.”

David R. Cornblath, MD, Baltimore, USA, said, “I feel that the pleotherapy approach has an enormous potential for the CMT community and other neurologic diseases as well. As a consultant to Pharnext, I look forward to contributing to the future success of this approach.”

About the Clinical Trial
In this double-blind, placebo-controlled Phase 2 clinical trial, 80 patients with mild to moderate CMT type 1A received either placebo or one of three escalating doses of PXT-3003 orally for one year. Preliminary safety and tolerability data were obtained together with the first efficacy data. The Overall Neuropathy Limitations Scale (ONLS) and the Charcot-Marie-Tooth Neuropathy Score (CMTNS) were the main efficacy endpoints. Other clinical outcomes and electrophysiological measures were also evaluated.

About CMT 1A

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 100,000 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.

About Pharnext

Pharnext is an advanced clinical stage biopharmaceutical company developing new therapeutics that simultaneously target multiple key disease pathways for severe orphan and common neurological diseases. The proprietary research and development platform of Pharnext is based on network pharmacology. It allows the development of synergic combinations of repositioned drugs: pleodrugs. The company’s two lead pleodrugs are PXT-3003 for the treatment of Charcot Marie Tooth type 1A (Phase 2 clinical trial completed) and PXT-864 for Alzheimer’s disease (Phase 2 clinical trial ongoing) and other neurological indications (Parkinson’s disease, ALS).

To be notified of the phase III trial, please join the Global Registry for Inherited Neuropathies (GRIN) at
For more information on Pharnext, visit

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  1. Rachel Craythorne

    I have CMT1A and would like to be in the trial but come from the Uk who would I need to get in contact with

  2. Barb Fulton

    Is this drug available for patients, yet?

  3. Bob

    Courtney, is it safe to assume that joining the registry is the only step to take in wanting to participate. Do the clinicians simply access the registry and pull likely participants from it and will initiate any contact.


    • courtney

      By registering and agreeing to be contacted by HNF, you will receive an email as the clinical sites open up in the USA for PXT-3003 and other eligible clinical trials. The clinicians do not have access. The patients data is de-identified.

  4. mary

    i have cmt 4b2,can i use or test drug pxt-3003

  5. charles

    I have cmt and would like to participate in the clinical trial.

    • courtney

      Please join the Global Registry for Inherited Neuropathies (GRIN) at Thank you for your comment.

  6. carla bendo

    I have type 2 CMT
    But would love to participate in the trial x

    • Ronald Riskevich

      I have CMT type X. Would I benefit from PXT-3003? Let me know any information you have. Thank-you

      • Allison Moore

        Ronald, thank you for posting. PXT-3003 is being investigated at this time only for PMP22 duplication (CMT1A). There are potential therapies on the horizon for x-linked forms. Please be sure to sign up for the HNF CMT Update Newsletter which is free to be kept informed of clinical studies. In addition, I would suggest joining the patient registry at


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