Abstract Details

Title Evaluation of Total Binding Antibodies Against rAAVrh74 in Patients with Duchenne Muscular Dystrophy

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P14 - Poster Session 14 (11:45 AM-12:45 PM)

Poster/Presentation
Number 11-005

Objective The objective of this study was to evaluate total binding antibodies against rAAVrh74 in patients with DMD.

Background

Adeno-associated virus (AAV) vectors have become the vehicle of choice for gene transfer therapy for Duchenne muscular dystrophy (DMD). The rAAVrh74 serotype efficiently transduces tissues impacted by DMD, including skeletal and cardiac muscle, and was therefore selected to develop a DMD gene therapy expressing a functional, shortened dystrophin protein. Successful gene transfer, however, requires patient screening for pre-existing AAV antibodies since these can limit therapeutic potential and pose safety concerns.

Design/Methods Eligible patients were ≥4 to <18 years old with genetically confirmed DMD and were excluded from the study if they lived with a person who had exposure to rAAVrh74 or other gene transfer therapy, or if they received prior treatment with gene transfer therapy. A single blood sample was obtained from each patient and anti-rAAVrh74 antibodies were measured by enzyme-linked immunosorbent assay. Total binding antibody level <1:400 was defined as ‘not elevated’. Primary endpoint was the percentage of subjects with elevated total antibody titers to rAAVrh74.

Results

Previously presented results from 53 enrolled patients (out of 100 planned) showed that overall, 15.1% (8/53) of patients were seropositive, with pre-existing elevated (≥1:400) total antibody titers to rAAVrh74; there was no association between seroprevalence and age in patients with DMD aged >4 to <18 years. In the 8 seropositive patients, titers to rAAVrh74 ranged from 1:400 to 1:3200. Final results from all patients enrolled in the study will be presented.

Conclusions Most patients with DMD were found to be negative for pre-existing antibodies to rAAVrh74, supporting the broad applicability of rAAVrh74-based gene transfer therapies in this population.

Authors/Disclosures
Natalie Goedeker, NP (Washington University in Saint Louis) PRESENTER	Miss Goedeker has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis Gene Therapies.
Danielle A. Griffin	Ms. Griffin has stock in Sarepta Therapeutics. Ms. Griffin has received intellectual property interests from a discovery or technology relating to health care.
	No disclosure on file
Sourav Santra	Sourav Santra has received personal compensation for serving as an employee of Sarepta Therapeutics.
	No disclosure on file
	No disclosure on file
Craig M. Zaidman, MD (Washington University in St Louis)	Dr. Zaidman has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for sarepta. The institution of Dr. Zaidman has received research support from Washington University in St Louis. The institution of Dr. Zaidman has received research support from Novartis.

��ɫ��

��ɫ��