Solid Biosciences noted that its response to the agency requests for further information about manufacturing as well as updated safety and efficacy data on all dosed patients led to the lift.
Solid Biosciences has announced that the FDA has lifted its clinical hold on the company’s phase 1/2 clinical trial of SGT-001, its gene therapy candidate for Duchenne muscular dystrophy (DMD), dubbed IGNITE DMD (NCT03368742). The trial was placed on hold in November 2019, after the third serious safety incident in the trial since its inception in 2017.1
In July 2020, the regulatory agency requested further information about manufacturing, as well as updated safety and efficacy data on all dosed patients, after which it offered direction on total viral load to be administered per patient. Solid’s response to the requests was deemed satisfactory by the FDA, thus the lift on the hold.
“We are pleased that our team was able to address the FDA’s clinical hold questions, allowing us to restart the trial,” said Carl Morris, PhD, chief scientific officer, Solid Biosciences, in a statement. “We are working diligently to complete all activities necessary to resume dosing, which we expect to occur in the first quarter of 2021.”
At the time of the clinical hold, the company said in a statement that 1 of 3 patients who were dosed at a 2E14 vg/kg dose in late October 2019 had experienced a serious adverse event (SAE) deemed related to the study drug that was characterized by complement activation, thrombocytopenia, a decrease in red blood cell count, acute kidney injury, and cardio-pulmonary insufficiency. Although, neither cytokine- nor coagulopathy-related abnormalities were observed. The patient is currently recovering and being monitored by his care team.2
The company noted that it supplied the FDA with data assessments from the 6-Minute Walk Test (6MWT) and North Star Ambulatory Assessment (NSAA) for all patients in the IGNITE DMD trial. To date, there have been no additional drug-related adverse events (AEs) reported out to the 30-month mark post-dose.
Solid noted that in efforts to mitigate the risk of serious drug-related AEs, it has amended the trial protocol to include the prophylactic use of both the anti-complement inhibitor eculizumab (Soliris; Alexion) and a C1 esterase inhibitor, as well as an increase in the prednisone dose in the first month post-dose.
Additionally, the maximum weight of the next 2 patients to be dosed will be reduced to 18 kg per patient, with the safety outcomes for 2 patients driving the weight gain for the subsequent patients dosed. This reduction, as well as the delivery of fewer viral particles as a result of the manufacturing improvements, will reduce patients’ total viral load while continuing dosing at the 2E14 vg/kg dose.
As part of its efforts to improve those manufacturing processes, Solid implemented and shared with the FDA changes that remove the majority of empty viral capsids, allowing target dosing to be achieved with fewer viral particles. Solid announced that it replied with data from a new, quantitative, in vitro microdystrophin expression assay that revealed comparability between SGT-001 manufactured by the 2 different processes.
In February 2019, preliminary findings from IGNITE-DMD showed positive signs for Solid Biosciences’ microdystrophin gene transfer therapy, which led to the company’s desire to dose escalate as planned and as soon as possible.3