Two Drugs Can Be Better Than One
By combining already established drugs in lower doses,
PLEOTHERAPY shows promise in improving targeted therapy
and reducing costs.
By Mike Botta, Contributing Editor
Pharnext, a clinical-stage biopharmaceutical company that develops therapeutics for neurodegenerative diseases for which there currently are no cures and existing therapies
available, has pioneered a new paradigm called
It centers on a blending of drugs previously
established and targeted for the treatment of certain
disorders that, when combined in optimal lower
doses, can be repositioned and formulated into new,
effective therapies for fighting other maladies, such
as Alzheimer’s disease.
To learn more about this new strategic approach
to drug development, Pharmaceutical Processing
asked Pharnext’s Rodolphe Haij, Ph.D., Chief
Pharmacology Officer, about the PLEOTHERAPY
concept and the company’s plans to further develop
the breakthrough process. Below are edited excerpts.
Q: Please explain the PLEOTHERAPY
approach to fighting diseases and what
led to the development of this new
Rodolphe Haij: Pharnext was founded in April
2007 by a group of experienced entrepreneurs and
renowned scientists, including our CEO Professor
Daniel Cohen—a pioneer of modern genomics.
Pharnext’s innovative PLEOTHERAPY R&D
approach is based on the multifactorial nature of
diseases (even when monogenic) as well as network
pharmacology. This technological platform allows
the identification of the thousands of molecules
possibly involved in a disease, which is called the
From this molecular map generated from big
Genomic Data, we then systematically deduce novel
and safe synergistic1 combinations of repositioned
drugs that targets simultaneously several disease
pathways. These novel therapeutics, called
PLEODRUG, are then developed at new optimal
lower doses and under new formulations for optimal
effect. They offer several key advantages, including
high efficacy, excellent safety, fast development
timelines as well as robust intellectual property.
PLEOTHERAPY is universally applicable to any
disease or compound, regardless of development
stage or lifecycle status, and has been endorsed by
world-renowned scientists and institutions.
Q: For the PXT3003 therapy designed to
fight Charcot–Marie–Tooth disease (CMT), a
hereditary motor and sensory neuropathy,
what drugs were combined, or repositioned, in
Haij: PXT3003 is our lead PLEODRUG currently in
Phase 3 development for the treatment of Charcot-Marie-Tooth disease type 1A (CMT1A) in adults.
PXT3003 is an oral fixed-low dose combination of
baclofen, naltrexone hydrochloride, and D-sorbitol
given twice daily.
It 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.
Q: When is Phase 3 for PXT3003 expected to
conclude and, if successful, when might it be
submitted for regulatory approvals?
Haij: Top line results from our ongoing pivotal
Phase 3 trial evaluating PXT3003 for the
treatment of Charcot-Marie-Tooth disease type
1A (CMT1A) in adults are expected in the second