Safety, Tolerability, and Efficacy of Dose Escalation of DT-DEC01 Therapy in DMD Patients 12 Months After Systemic-Intraosseous Administration

Topic:

Clinical Trials

Poster Number: V171

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 an X-linked progressive, degenerative disease caused by dystrophin gene mutations. Currently, no cure exists. This report confirms the safety and tolerability of dose escalation of DT-DEC01, a novel Dystrophin Expressing Chimeric (DEC) cell therapy after systemic-intraosseous administration to DMD patients.

Methods
This pilot, open-label study enrolled five DMD patients, of age 6-15 years old into two single-dose cohorts : A) 2×10^6 DEC cells/kg (n=3) and B) 4×10^6 DEC cells/kg (n=2). Safety was assessed by monitoring Adverse Events (AEs), Serious Adverse Events (SAEs) and the presence of anti-HLA and DSA antibodies. Efficacy was measured through standard functional tests including the 6MWT and NSAA timed function tests in ambulatory patients, and PUL test, muscle strength, electromyography (EMG), echocardiography (ECHO), spirometry, and daily activity in both, ambulatory and non-ambulatory patients.

Results
Both doses of DT-DEC01 were safe, well-tolerated and effective, as confirmed by the absence of therapy-related AE, SAE and a lack of DSA antibodies in both cohorts: A) up to 24 months and B) up to 18 months after systemic-intraosseous administration of DT-DEC01 therapy. An analysis of preliminary efficacy at 12 months revealed dose-dependent improvements in functional tests. While functional improvements and increased daily activities were similar in patients from both cohorts, the higher dose (4×10^6 cells/kg) of DT-DEC01 demonstrated more significant benefits in cardiac and pulmonary function, as confirmed by echocardiography and spirometry, especially in older wheelchair-bound patients.

Conclusions
This study confirmed the long-term safety and tolerability of dose escalation of DT-DEC01 therapy as indicated by the absence of study-related AE, SAE and DSA, confirming the lack of immune response up to 24 months after systemic-intraosseous administration. Additionally, we observed dose-dependent improvements in cardiac and pulmonary function. These positive systemic effects of DT-DEC01 in adolescent DMD patients are encouraging and suggest the potential to halt the progressive decline in cardiac and pulmonary function, which is responsible for the premature death of DMD patients.