The adeno-associated viral vector-mediated gene transfer therapy being tested in the trial has experienced a number of setbacks, most recently when the FDA put the trials on hold in response to a reported case of acute kidney injury which prompted the agency to impose the clinical hold almost a year ago and asking to see more data before lifting the hold.
The request led the biotech to share further information on the SGT-001 gene therapy manufacturing process and the latest safety and efficacy data; the additional information apparently provided sufficient enough information to persuade the FDA to lift the clinical hold allowing the trial to eventually resume. The information shared was from a quantitative in vitro microdystrophin expression assay that was designed to show the comparability of SGT-001 manufactured under the old and new processes.
“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, Ph.D., Chief Scientific Officer at Solid Biosciences. “We are working diligently to complete all activities necessary to resume dosing, which we expect to occur in the first quarter of 2021.”
The clinical trial will resume dosing using a gene therapy that has been made under a revised manufacturing process that is intended to remove most empty viral capsids which allows the biotech to cut the total viral load without reducing the dose; the focus on the viral load reflects concerns about the systemic delivery of AAV vectors that can damage organs and cause inflammation.
Other precautions are also being taken to manage the potential risk posed by SGT-001, according to Solid Bio the maximum weight of the first 2 patients to receive the drug candidate after the hold lifts will be at 18kg; the dose of the drug is determined by weight, meaning that heavier patients receive more vector genomes. Adverse events seen in some gene therapy trials have happened in heavier patients who have received higher viral loads due to weight dependency of the drug dosing.
Protocols are being amended to include the prophylactic use of eculizumab which is an anti-complement inhibitor and C1 esterase inhibitor while increasing the prednisone dose in the month after treatment to help further mitigate the potential of SGT-001 to cause harm. Shares in Solid Bio took a hit dropping to $2 apiece after the FDA clinical hold, now they have increased by 70% in response to the end of the hold.
These changes position the biotech to resume the pursuit of a DMD gene therapy leader Sarepta Therapeutics which is experiencing setbacks of their own as the FDA has asked the company to use an extra potency assay in a planned clinical trial. Additionally, Pfizer is in this race but has also run into safety issues that could give another company an edge.
