After the setback of having to do a second Phase 3 clinical trial, Pharnext’s ongoing drug trials for PXT3003 show positive results in people with CMT1A.
Update, October 2026: PXT3003 did not pan out. In December 2023, Pharnext reported that its second phase 3 trial did not show that PXT3003 improved disability in CMT1A as measured by the ONLS; the company blamed an unexpected improvement in the placebo group (Fierce Biotech, December 11, 2023). On August 22, 2024, the Paris Commercial Court placed Pharnext in judicial liquidation (Option Finance, in French). Correction, October 10, 2026: That second trial was not the only later phase 3, though. A separate Chinese phase 3 trial in 176 people, run by Pharnext’s partner Tasly, has since reported a statistically significant but modest ONLS result: a between-group difference of −0.249 points at 15 months.1 It has to be weighed against the failed trial and the earlier evidence, and it is not, by itself, proof of approval or definitive clinical benefit. In September 2026, Néovacs reported a binding letter of intent from an unnamed American biopharmaceutical company to acquire PXT3003 intellectual property and know-how, with exclusivity until October 15, 2026.2 Pharnext’s own website is gone, so some links below point to archived copies. For the full arc, see Three “Treatable CMT” Stories, and What the Market Taught Us.
The combination of existing drugs in PXT3003 appears to reduce or stabilize symptoms as measured by the Overall Neuropathy Limitations Scale (ONLS) — a diagnostic instrument, first published in 2006, in the form of a simple questionnaire to assess your level of disability, no matter what kind of CMT you may have:
📄 Graham RC, Hughes RAC (2006). “A modified peripheral neuropathy scale: the Overall Neuropathy Limitations Scale.” Journal of Neurology, Neurosurgery & Psychiatry 77: 973–976.
PXT3003 is classified as a “pleodrug” developed through “pleotherapy.” The pleo- prefix is Greek in origin, and it means “more,” in reference to the combination of multiple drugs. Dr. Daniel Cohen, CEO and co-founder of the Paris-based Pharnext, explains the concept:
Pleotherapy assumes that any molecule can be used for different functions. The Pleotherapy approach combines low doses of existing drugs to develop treatments for new indications using big data analysis of genomics and pharma, to match the properties of drug combinations with specific diseases. Pharnext’s use of drugs that have been approved by the FDA, combined with its proprietary data analysis, allows the company to shave as much as seven years off the typical 15- to 20-year drug approval process.
—Daniel Cohen, Pharnext CEO
What drugs are combined in this “pleodrug?”
PXT3003 “is an oral fixed-low dose [taken as 5 mL of liquid] combination of baclofen, naltrexone hydrochloride, and D-sorbitol given twice daily,” according to Pharnext’s Chief Pharmacology Officer, Dr. Rodolphe Hajj:
[PXT3003] has multiple main mechanisms of action: an inhibition of PMP22 gene overexpression associated with a synergistic myelination improvement, direct nerve protection, and additional positive effects on: muscle cells, neuromuscular junctions, and immune cells. Positive data from the PXT3003 Phase 2 program served as proof-of-concept for this novel, pleotherapy approach to drug development.
CMT News further explains,
The combination of the three treatments is intended to reduce the levels of PMP22 by targeting the pathways that promote PMP22 gene expression. Furthermore, sorbitol is thought to act as a “chaperone,” which increases the chances of the PMP22 protein being correctly processed and becoming functional. This should result in lower overall levels of nonfunctional PMP22, resulting in less disruption of the surrounding cells and more functioning PMP22 that can be incorporated into the myelin sheath.
In a rat model of CMT1A, PXT3003 successfully reduced PMP22 gene expression and increased myelination more effectively than a single treatment. Increased myelination should improve the transmission of nerve signals and protect nerve cells from damage.
PXT3003 may also have beneficial effects on other cells such as muscle cells, cells at the junction between muscle and nerve cells, and immune cells.
Acceleron’s ACE-083 is the only other drug currently in clinical trials for CMT after failing to produce results for muscular dystrophy patients. Maybe it will prove to have some benefit for people with CMT.
Acceleron’s ACE-083 is the only other drug that was recently tested with CMTers. It failed to produce results with both MD and CMT patients alike.
What are your hopes and questions about drug research for CMT? Let me know in the comments.
Notes
- Liu et al., “Phase III Clinical Trial of PXT3003.” The trial is registered as NCT05092841. ↩︎
- Néovacs, “Nouvelle publication scientifique.” ↩︎
Sources
- Liu, Xiaoxuan, Wanqian Cao, Hongli Li, et al. “A Phase III Clinical Trial of PXT3003 in Chinese Patients with Charcot-Marie-Tooth Disease Type 1A.” iScience 29, no. 9 (2026): 117284. https://doi.org/10.1016/j.isci.2026.117284.
- Néovacs. “Nouvelle publication scientifique des résultats de phase III de PXT3003 en Chine.” Actusnews, September 9, 2026. https://www.actusnews.com/en/neovacs/pr/2026/09/09/nouvelle-publication-scientifique-des-resultats-de-phase-iii-de-pxt3003-en-chine.
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