4D Molecular Therapeutics’ Fabry Gene Therapy put on FDA-mandated hold

pharmafile | February 7, 2023 | News story | Research and Development  

4D Molecular Therapeutics has had its gene therapy programme 4D-310 put on clinical hold by the FDA after adverse side effects were reported in trial participants.


4D-310 is an investigational gene therapy that uses a proprietary vector to deliver a functional copy of the GLA gene, which encodes for the enzyme alpha-galactosidase A. Fabry disease mutates GLA, producing altered forms of the enzyme which leads to the intracellular accumulation of toxic substances throughout the body. This then eventually leads to progressive organ dysfunction.


Three cases of atypical hemolytic uremic syndrome (aHUS), a kidney condition characterised by an increased risk of blood clots in the organ, were reported in the first six patients enrolled across two trials. This led to 4D pausing enrollment.


All cases were resolved in two to four weeks, however one instance qualified as a grade four dose-limiting toxicity, which necessitated temporary hemodialysis in a 69-year-old man who had underlying kidney dysfunction. This led to the FDA’s clinical hold notice, however it acknowledged the company’s preemptive recruitment pause and allowed the programme to keep its current Investigational New Drug application open.


4D was also instructed to continue long-term follow-ups with all of the patients dosed with 4D-310. This data ‒ noting the safety, efficacy and cardiac biopsy for 4D-310 ‒ will then be presented at the WORLD Symposium in February.


James Spargo 

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