Long-term Safety and Efficacy of DT‑DEC01 Therapy in Duchenne Muscular Dystrophy Patients 24 Months After Systemic Intraosseous Administration

Topic:

Clinical Trials

Poster Number: V172

Author(s):

Maria Siemionow, MD, PhD, DSc, University of Illinois at Chicago, Bieganski Grzegorz, MD, Poznan University of Medical Sciences, Jacek Wachowiak, MD, PhD, Poznan University of Medical Sciences, Jaroslaw Czarnota, MD, Hospital MedPolonia, Poznan, Krzysztof Siemionow, MD, PhD, Dystrogen Therapeutics Corp., Adam Niezgoda, MD, PhD, Poznan University of Medical Sciences, Anna Ziemiecka, MSc, Dystrogen Therapeutics Corp., Katarzyna Bozyk, MSc, Dystrogen Therapeutics Corp., Ahlke Heydemann, PhD, University of Illinois at Chicago

Introduction:
Duchenne muscular dystrophy (DMD) is a lethal disease that results in muscle degeneration due to a dystrophin gene mutation. This study presents the long-term safety and efficacy of DT DEC01, a novel Dystrophin Expressing Chimeric (DEC) cell therapy, assessed after systemic-intraosseous administration.

Methods:
A single dose of DT-DEC01 therapy (2×10^6 cells/kg) was administered intraosseously to three DMD boys of age 6-15 years old, without immunosuppression. Safety was assessed by monitoring of Adverse Events (AE), Serious Adverse Events (SAE), DSA antibodies and lymphocytes immunophenotyping. Efficacy was evaluated by: the 6MWT, NSAA, PUL test, grip strength, electromyography (EMG) – Motor Unit Potentials (MUP) duration and daily activity assessed by step/arm movements count.

Results:
No study-related AE, SAE or DSA antibodies were reported during the 24-month follow-up. Immunophenotyping confirmed normal distribution and activity of B-cells, T-cells and NK-cells. The 12-month efficacy assessment demonstrated the following:
Patient #1 (6-year-old, ambulatory, exon 3-12 deletion): Maintained 6MWD, improved standing from supine and 10-meter run; maintained PUL test, improved grip strength by 65%; EMG increased MUP in: deltoideus by 25%, rectus femoris by 11%, gastrocnemius by 53% and increased daily step count by 74%.
Patient #2 (15-year-old, non-ambulatory, exon 48-50 deletion): Improved grip strength by 15% and PUL test by 13%; EMG increased MUP duration in: deltoideus by 34%, biceps by 149%, rectus femoris by 64%, gastrocnemius by 33% and increased daily activity by 184%.
Patient #3 (6-year-old, ambulatory, nonsense mutation): Improved: 6MWD by 18%, standing from supine and PUL test; EMG increased MUP duration in: deltoideus by 60%, biceps by 32%, rectus femoris and gastrocnemius by 11% and increased daily step count by 54%.

Conclusions:
This study confirmed the long-term safety of DT-DEC01 therapy as evidenced by the absence of AE, SAE, DSA and the lack of immune response up to 24 months after systemic-intraosseous administration. Efficacy was confirmed through improvements in standard functional tests, an increased MUP duration by EMG and enhancements in daily step/arm activity. These findings introduce DT-DEC01 as a promising new therapeutic option for all DMD patients regardless of the gene mutation.