Allogeneic MSC Therapy Demonstrates Safety in Patients With Duchenne Muscular Dystrophy


There were no dose-limiting toxicities, serious adverse events, nor infusion-related reactions among 6 patients treated with ENCell’s investigational EN001 therapy.

ENCell’s EN001, an investigational product consisting of allogeneic early-passage mesenchymal stem cells (MSCs) derived from Wharton’s Jelly in the umbilical cord, has demonstrated safety in 6 patients with Duchenne muscular dystrophy (DMD) who were treated in a phase 1 clinical trial (NCT05338099), along with efficacy in some patients. The data were presented in a poster authored by Jee Hun Lee, MD, and colleagues at the American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting, held May 16-20, in Los Angeles, California.

In terms of safety, there were no dose-limiting toxicities, serious adverse events (AEs), nor infusion-related reactions. There were 18 AEs observed among the treated group in total; the AEs were deemed mild, and the patients recovered from them within 5 days of onset. All AEs were classified as unexpected. Six AEs occurred in the low dose cohort (n = 3), which received 5.0x105 cells/kg, and 12 AEs occurred in the high dose cohort (n = 3), which received 2.5x106 cells/kg. There were 16 adverse drug reactions, all of which were classified as unexpected, with 8 occurring in each dose cohort.

“EN001 was safe and well-tolerated at both low-dose and high-dose for DMD patients,” first author Lee, a professor in the Department of Pediatrics at Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, and colleagues wrote. “In addition, the data on treatment efficacy indicates that EN001 improved ambulatory capacity, pulmonary function, and muscle strength in some patients. This study suggests that allogeneic early-passage MSCs derived from Wharton’s Jelly might have a potent therapeutic effect for the treatment of DMD and can be used in all subtype-specific DMD patients.”

The trial evaluated patients with the North Star Ambulatory Assessment (NSAA) at baseline and at 12 weeks posttreatment. One patient (referred to as SD01-003) showed an improvement of 1 point from baseline on their NSAA total score and another patient (SD01-007) maintained a stable NSAA total score. The other 4 patients (SD01-001, SD01-002, SD01-005, and SD01-006) showed a decline of 3 to 8 points in NSAA total score.

On spirometry testing, SD01-001 showed an improvement in forced vital capacity (FVC) from 66% at baseline to 73% at 48 weeks posttreatment. SD01-006 showed an improvement in FVC from 87% at baseline to 90% at 24 weeks posttreatment and SD01-007 showed an improvement in FVC from 100% at baseline to 108% at 24 weeks posttreatment—for SD01-006 and SD01-007, this was their most recent follow-up. The other 3 patients showed a decline in FVC from baseline at their respective most recent follow-ups.

On a test of strength of the knee extensors, SD01-003 showed an improvement from 4.20 lbs at baseline to 5.45 lbs at 48 weeks posttreatment, SD01-005 showed an improvement from 1.85 lbs at baseline to 2.30 lbs at the most recent follow-up of 36 weeks, and SD01-006 showed an improvement from 3.25 lbs at baseline to 4.70 lbs at the most recent follow-up of 24 weeks. The other 3 patients showed a decline from baseline at their most recent follow-up. It was additionally noted that 4 of 6 patients showed a decrease from baseline in their serum creatine kinase (CK) level at their most recent follow-up.

At the time of treatment, SD01-001 was aged 11 years, SD01-002 was aged 9 years, SD01-003 was aged 14 years, SD01-005 was aged 15 years, SD01-006 was aged 11 years, and SD01-007 was aged 10 years. SD01-001, SD01-002, and SD01-003 received the trial’s low dose and SD01-005, SD01-006, and SD01-007 received the trial’s high dose. The patients received EN001 as a 1-time administration, which was delivered intravenously. Lee and colleagues noted that EN001 had previously demonstrated positive results in preclinical mouse model research including antiapoptosis effects, antifibrosis effects, muscle regeneration, serum CK reduction, and motor function improvement.

1. Lee J, Lee J, Kim M, Jeon HB, Chang JW. An open-label, dose-escalation, phase 1a study to evaluate safety, tolerability, and exploratory efficacy of intravenous injection of allogenic early-passage mesenchymal stem cells (MSCs), derived from Wharton’s jelly in the umbilical cord, in patients with Duchenne muscular dystrophy. Presented at: American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting. May 16-20, 2023; Los Angeles, CA. Poster #952.
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