FDA grants orphan drug status to EN001 stem cell therapy for CMT
Clinical trial testing therapy in South Korea due for completion this year
The U.S. Food and Drug Administration (FDA) has granted orphan drug status to Encell’s EN001, an investigational stem cell therapy for Charcot-Marie-Tooth disease (CMT).
This designation is intended to accelerate the development of therapies designed to prevent, diagnose, or treat rare diseases — those affecting fewer than 200,000 people in the U.S. It comes with certain incentives, such as tax credits, fee exemptions, and seven years of market exclusivity if the therapy is ultimately approved.
Meanwhile, a Phase 1b clinical trial (NCT06328712) testing EN001’s safety and efficacy in people with CMT type 1A (CMT1A), the most common type of CMT, is ongoing in South Korea. The study is expected to be completed this year, according to Encell.
“The U.S. FDA’s orphan drug designation for EN001 is a significant milestone that will accelerate the clinical development of this therapy. We are committed to successfully completing the ongoing Phase 1b trial and ensuring that CMT patients gain timely access to this innovative treatment,” an Encell representative said in a company press release.
Phase 1b trial aims to determine maximum tolerated dose of EN001
CMT is a group of neuromuscular conditions that affect the peripheral nervous system — the network of nerves outside the brain and spinal cord that are responsible for sensation and movement. The disease’s symptoms are progressive, and include sensory loss and muscle weakness. There are six types of CMT, classified by factors such as the way the disease is inherited and its severity.
CMT1A is caused by mutations in the PMP22 gene that result in excessive levels and loss of function of a protein with the same name, which results in disruption of the myelin sheath that surrounds nerve fibers. This protective coating helps nerve fibers send electric signals.
EN001 uses mesenchymal stem cells derived from Wharton’s jelly, a gel-like substance found within the umbilical cord. Mesenchymal stem cells may generate several types of cells and have been shown to increase myelin production and improve peripheral nerve function.
In preclinical studies, these stem cells were shown to migrate to and regenerate damaged nerves, according to Encell.
The therapy was tested in a small Phase 1 trial (NCT05333406), enrolling adults with CMT1A, who received either a low or high dose of EN001 (0.5 or 2.5 million cells/kg), through intravenous (into-the-vein) administration. The results demonstrated that EN001 was safe and well tolerated.
Additionally, the therapy appeared to be effective at improving motor function and nerve conduction, and at reducing disease severity, with a more significant effect in patients who received the higher EN001 dose.
The ongoing Phase 1b trial, involving participants ages 19 and older, is testing two doses of EN001 — containing either 1.25 or 2.5 million cells/kg — given in four-week intervals. The trial aims to determine dose-limiting adverse effects for up to eight weeks and the maximum tolerated dose of EN001, meaning the highest dose that does not cause unacceptable side effects. The results will be used to recommend a Phase 2 trial dose.
Additionally, the trial is assessing efficacy for up to six months, by analyzing patients’ symptom severity, functional disability, motor function, and nerve conduction. It will also assess EN001’s effects on patient-reported quality of life.
About the Author
