The FDA have placed a clinical hold on Sarepta’s Phase 1/2a gene therapy clinical trial assessing Sarepta’s AAVrh74.MHCK7 gene therapy for Duchenne muscular dystrophy (DMD), following the discovery of trace levels of DNA fragments in research-grade plasmids supplied by an undisclosed third-party manufacturer.
A letter from the FDA was received by the Nationwide Children’s Hospital, which is carrying out the clinical trial, notifying the institute that a trace amount of DNA fragment was found in research-grade plasmids in one lot of the microdystrophin gene therapy material, following quality assurance testing. Subsequently the FDA placed the trial on a clinical hold. However, none of the plasmids demonstrating the presence of the fragment DNA were given to any of the four patients enrolled in the trial. An earlier lot of the plasmids from the same supplier had been used in the patients, but patient biopsies also showed no presence of the fragment. According to preliminary in vivo testing, the trace fragment in question does not result in protein expression and is quickly cleared.
In response to the FDA’s letter, Sarepta have begun work on a corrective action plan which includes a commitment for the use of Good Manufacturing Practice grade plasmid material in order to avoid an issue like this in the future. It is not expected that this incident will cause a material delay in patient dosing in the trial, currently expected to conclude by the end of 2018.
“We understand the source of the issue, have been given clear guidance on how to address it, and have a plan to keep our clinical program on track. We intend to rapidly respond to the FDA’s clinical hold letter, including a commitment to the Agency to only use GMP-s plasmid. Independently, we will also request a meeting with the Agency to discuss the micro-dystrophin program with the goal of commencing a pivotal trial by year-end 2018.” commented Sarepta President and CEO Doug Ingram.
The clinical hold comes a month after Sarepta reported promising preliminary trial data, with reported results indicating that the therapy has the potential to halt or reverse the effects of the genetic disease.
Source: Sarepta Therapeutics Announces that Phase 1/2a Duchenne Muscular Dystrophy (DMD) Micro-Dystrophin Gene Therapy Trial Placed on Clinical Hold Due to an Out-of-Specification Production Lot; No Observed Safety Events Press Release