Safety and Efficacy of DT‑DEC01 Therapy in Non-Ambulatory Duchenne Muscular Dystrophy Patients up to 24 Months after Systemic Administration

Topic:

Clinical Trials

Poster Number: O163

Author(s):

Maria Siemionow, MD, PhD, DSc, University of Illinois at Chicago, Dystrogen Therapeutics Corporation, Grzegorz Biegański, MD, Poznan University of Medical Sciences, Jacek Wachowiak, MD, PhD, Poznan University of Medical Sciences, Jarosław Czarnota, MD, Hospital MedPolonia, Krzysztof Siemionow, MD, PhD, University of Illinois at Chicago, Dystrogen Therapeutics Corporation, Adam Niezgoda, MD, PhD, Poznan University of Medical Sciences, Anna Ziemiecka, MSc, Dystrogen Therapeutics Corporation, Katarzyna Bożyk, MSc, Dystrogen Therapeutics Corporation, Ahlke Heydemann, PhD, University of Illinois at Chicago

Introduction:
Duchenne muscular dystrophy (DMD) is an X‑linked disease leading to progressive muscle degeneration and premature death. Long-term safety and efficacy of DT-DEC01, Dystrophin Expressing Chimeric (DEC) cell therapy, was evaluated in non-ambulatory DMD patients after systemic-intraosseous administration.

Methods:
Three non-ambulatory DMD patients (age 11-16) received DT-DEC01 therapy at doses of 2×106, 4×106 and 6×106 cells per kg body weight respectively, without immunosuppression. Safety after DT-DEC01 administration was assessed by monitoring Adverse Events (AE), Serious Adverse Events (SAE), and Donor-Specific Antibodies (DSA). Efficacy was evaluated using the PUL 2.0 test, grip strength, electromyography (EMG) for Motor Unit Potentials (MUP) duration, echocardiography, spirometry, and daily activity measured by wristband arm movements counts.

Results:
No study-related AE, SAE or DSA were reported up to 24 months. Efficacy assessments in non-ambulatory patients demonstrated following improvements:
Patient #1 (15-year-old, exon 48-50 deletion) demonstrated improvements in: echocardiography EF by 12%, MUP duration (deltoideus by 53%, biceps brachii by 23%), arm movements by 9% up to 18 months, with sustained improvements in: PUL score by 5%, grip strength by 6%, and spirometry by 17% up to 24 months.
Patient #2 (11-year-old, exon 52 deletion) exhibited improvements in: echocardiography by 17% up to 12 months, PUL score by 5% and MUP duration (deltoideus by 19%, biceps brachii by 51%) up to 18 months, spirometry 59%, and arm movements by 1150% up to 24 months.
Patient #3 (16-year-old, nonsense mutation) currently at 12 months post-DT-DEC01 administration showed improvements in PUL score by 6%, grip strength by 34%, echocardiography by 11%, and EMG MUP duration (deltoideus by 49%, biceps brachii by 29%).

Conclusions:
This study confirmed the long-term safety of DT-DEC01 therapy in non-ambulatory DMD patients as evidenced by the absence of AE, SAE, and DSA up to 24 months post systemic intraosseous administration. Efficacy was supported by sustained improvements in functional tests, including EMG, echocardiography and spirometry up to 24 months. These findings introduce DT-DEC01 as a promising therapeutic option for all DMD patients, regardless of gene mutation or disease progression.