The trial was initially placed on hold in November 2019 due to safety concerns.
Shares of Solid Biosciences skyrocketed more than 70% in premarket trading after the company announced the U.S. Food and Drug Administration (FDA) lifted the clinical hold on the company’s IGNITE DMD Phase I/II clinical trial.
The trial was initially placed on hold in November 2019 due to safety concerns. A patient experienced a serious adverse event that was related to SGT-001, a novel adeno-associated viral vector-mediated gene transfer. Solid made several attempts to address the clinical hold, including adding measures to improve patient safety, as well as updated manufacturing process improvements. In July of this year, the FDA requested further manufacturing information, updated safety and efficacy data for all patients dosed, and direction on total viral load to be administered per patient. Solid Biosciences delivered the requested information to the regulatory agency.
This week, the FDA said the company satisfactorily addressed all clinical hold questions and gave Cambridge, Mass.-based company the go-ahead to resume the study.
Carl Morris, chief scientific officer of Solid Biosciences, said he is pleased the company was able to address the FDA’s questions regarding the clinical hold. Morris said he anticipates the Phase I/II study to restart in the first quarter of 2021.
SGT-001 is a novel adeno-associated viral (AAV) vector-mediated gene transfer therapy designed to address the underlying genetic cause of Duchenne muscular dystrophy, which is caused by mutations in the dystrophin gene that result in the absence or near absence of dystrophin protein. SGT-001 delivers microdystrophin, a synthetic dystrophin gene, which encodes for a functional protein surrogate that is expressed in muscles and stabilizes essential associated proteins.
The development of SGT-001 has been difficult. The clinical hold slapped on the company in November was the second for the DMD treatment. In 2018, the FDA placed a clinical hold on the trial following the report of a serious adverse event. That hold was lifted in June 2018 after the company addressed the FDA’s concerns.
According to its announcement this morning, Solid provided manufacturing process changes that remove the majority of empty viral capsids, allowing target dosing to be achieved with fewer viral particles. This reduction in the total amount of virus delivered to each patient is intended to support safe dosing of SGT-001 for the duration of the IGNITE DMD trial, the company said. When the trial resumes, the next two patients dosed will receive 18 kg to begin and if the safety outcomes are well-maintained, the company said it could begin to increase the weight of the doses over time.
“This reduction, in conjunction with the delivery of fewer viral particles as a result of the Company’s manufacturing process improvements, will reduce patients’ total viral load while continuing dosing at the 2E14 vg/kg dose,” the company said in its announcement.
To mitigate the risk of serious drug-related adverse events, Solid is amending the trial protocol to include the prophylactic use of both anti-complement inhibitor eculizumab and C1 esterase inhibitor, and increasing the prednisone dose in the first month post-dosing.
Additionally, Solid Biosciences provided the FDA with updated safety and functional efficacy data (including 6-Minute Walk Test and North Star Ambulatory Assessment data) for all patients dosed to date in IGNITE DMD. There have been no additional drug-related adverse events up to 30 months post-dosing, the company said.
