FDA Grants Orphan Drug Designation to EN001 for Neuromuscular Disorder, CMT Disease

Author(s):

Gillian McGovern, Associate Editor

Currently, EN001 is undergoing evaluation in a phase 1b trial.

The FDA granted an orphan drug designation to EN001 (ENCell Co, Ltd) to treat patients with Charcot-Marie-Tooth (CMT) disease. This action follows safety and efficacy results from a phase 1 clinical trial (NCT05333406).^1,2

Image credit: gguy | stock.adobe.com

EN001 is a mesenchymal stem cell therapy that enhances cell longevity, optimizing the secretion of therapeutic molecules that are required for treatment. Once the agent is administered, it targets damaged nerves, promotes the secretion of regenerative factors, and facilitates remyelination in patients with CMT.¹

CMT is a hereditary neuromuscular disorder that causes progressive muscle weakness and deformities in the hands and feet. In severe cases, it can lead to vision and hearing impairment. CMT is one of the most prevalent rare diseases; however, there are currently no approved treatments available, making it a significant challenge for both patients and health care providers.¹

The open-label, dose-escalation phase 1 clinical trial (NCT05333406) that helped support the orphan drug designation for EN001 had enrolled patients with type 1a CMT. It was a first-in-human, 3+3 design clinical trial to evaluate the safety, tolerability, and maximum tolerated dose (MTD) of EN001. Patients were enrolled in a low dose group (5.0x10^5 cells/kg) in which they received an intravenous dose on day 0. Patients were evaluated over a 16-week duration.^2,3

The primary outcome measures included the following: incidence of adverse events (AEs) and/or serious AEs; determination of dose-limiting toxicity (DLT); MTD; vital sign abnormalities; frequency of clinically significant abnormalities; abnormalities of laboratory parameters; and number of participants with electrocardiography abnormalities. Secondary end points included changes from baseline in disease severity score, gait and balance functions, degree of muscle damage, and nerve regeneration potential.²

Results from June 2024 showed no DLT, serious AEs, or infusion-related responses among participants, demonstrating EN001’s safety. Exploratory efficacy evaluations also revealed significant improvements. The CMT Neuropathy Score version 2 had decreased by an average of 2.89 points (P = .0039) after 16 weeks, with the high-dose group showing a more pronounced reduction of 3.50 points (P= .0313).³

Additionally, further analysis indicated that patients receiving the high dose experienced clinical improvements in disease severity, with some moving from severe to moderate or from moderate to mild categories.³ Results from October 2024 showed that 3 patients receiving 2 doses of EN001 had no occurrences of DLT when assessed at 8 weeks post-administration. Notably, there were no serious AEs or injection-related reactions. Because of these findings, a phase 1b trial featuring a high-dose group (2.5x10^6 cells/kg) has been initiated and aimed to reach completion during 2025.^1,2

About the Trial

Trial Name: Determine the Safety and Dose of EN001 in Patients With Charcot-Marie-Tooth Disease (CMT) Type 1A

ClinicalTrials.gov ID: NCT05333406

Sponsor: ENCell

Completion Date: December 20, 2022

Additionally, EN001 is in the process of trying to expand its indications beyond CMT, including Duchenne muscular dystrophy and sarcopenia. These indications could further strengthen EN001’s potential as next-generation stem cell therapy in the muscular disease space.¹

“The US 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 [patients with CMT] gain timely access to this innovative treatment,” an ENCell representative commented in a news release.¹

REFERENCES

1. Businesswire. ENCell’s EN001 Receives Orphan Drug Designation from the U.S. FDA for Charcot-Marie-Tooth Disease. News release. March 6, 2025. Accessed March 6, 2025. https://www.businesswire.com/news/home/20250306675394/en/ENCell%E2%80%99s-EN001-Receives-Orphan-Drug-Designation-from-the-U.S.-FDA-for-Charcot-Marie-Tooth-Disease

2. Determine the Safety and Dose of EN001 in Patients With Charcot-Marie-Tooth Disease (CMT) Type 1A. ClinicalTrials.gov identifier: NCT05333406. Updated February 17, 2023. Accessed March 6, 2025. https://clinicaltrials.gov/study/NCT05333406

3. Businesswire. ENCell Presents the Phase 1 Clinical Trial Results of their Mesenchymal Stem Cell Therapy, EN001, for Charcot-Marie-Tooth Disease at the PNS conference. News release. June 26, 2024. Accessed March 6, 2025. https://www.businesswire.com/news/home/20240624485930/en/