4D Molecular Therapeutics has offered to add an immunosuppressive regimen during the administration of a Fabry disease gene therapy in order to continue with human testing and lift a clinical hold placed on the program by the FDA earlier this year.
The biotech announced that alignment had been reached with the agency on a proposed plan to lift the hold instituted in February on the phase 1/2 INGLAXA clinical trial for the gene therapy 4D-310. The treatment is meant for Fabry disease-related cardiomyopathy.
A hold was placed on the program when three cases of a kidney condition called atypical hemolytic uremic syndrome (aHUS) occurred in the first six patients dosed. The condition is associated with the formation of clots in the small blood vessels of the kidneys. 4DMT voluntarily halted enrollment after the cases came to light in January, but the FDA followed with an official hold.
“We are delighted to have reached an agreement with the FDA on our proposed plan to address the clinical hold and continue trial development,” said David Kirn, M.D., CEO of 4DMT. “We have shared with the FDA the totality of the most up-to-date clinical activity and safety data already generated from INGLAXA trials, as of August 2023, and look forward to progressing this critical work on behalf of all patients with Fabry disease.”
4DMT plans to conduct a single pre-clinical non-human primate study to evaluate the safety and biodistribution of intravenous 4D-310 along with the rituximab/sirolimus immunosuppressive regimen compared to a prior prednisone regimen. Results are expected to be submitted to the FDA in the second quarter of 2024.
The protocol has been amended to reflect the new immunosuppressive regimen, which 4DMT believes will mitigate the risk of aHUS following IV dosing of 4D-310.
4DMT previously presented data from just three patients showing improvements in several cardiac endpoints and transgene expression. More data from a total of six patients are expected in the first quarter of 2024.