NEW YORK – A recent meeting with the US Food and Drug Administration has given Sangamo Therapeutics confidence to seek accelerated approval for its investigational gene therapy for Fabry disease, isaralgagene civaparvovec, based on data from an ongoing Phase I/II trial.
Isaralgagene civaparvovec, also known as ST-920, is currently undergoing evaluation in the Phase I/II STAAR trial and has shown promising safety and efficacy, including evidence that the treatment improves kidney function. Fabry disease is caused by GLA mutations and leads to a buildup of a lipid called globotriaosylceramide, which in turn damages the kidneys, heart, nerves, eyes, gut, and skin. Renal deficiencies, such as decreased glomerular filtration rate, occur in patients with Fabry disease and can lead to end-stage renal disease and early death.
After more than a year of follow-up in 18 male and female patients treated in the STAAR trial with Sangamo's gene therapy, researchers saw statistically significant improvements in the mean and median estimated glomerular filtration rate (eGFR), resulting in a positive annualized eGFR slope.
Sangamo said that the FDA has agreed that the firm can use the eGFR slope at 52 weeks as an intermediate clinical endpoint supporting isaralgagene civaparvovec's efficacy in an accelerated approval application. Richmond, California-based Sangamo expects to release the STAAR trial dataset supporting accelerated approval in the first half of 2025 and anticipates submitting a biologics license application (BLA) for isaralgagene civaparvovec in the second half of 2025. If successful, this would allow the company to seek regulatory approval three years before it had originally planned and preclude the need for another registrational study.
Earlier this year, based on discussions with the FDA, Sangamo had expected to do a registrational study involving up to 25 patients that didn't involve a control arm. At the time, the firm said it wouldn't invest in conducting a registrational trial without a commercialization partner.
Now that Sangamo can use data from the STAAR trial to seek approval for this gene therapy, the firm said in a statement that it has "begun to execute BLA readiness activities for isaralgagene civaparvovec while continuing to advance ongoing business development discussions with potential collaboration partners."
According to Sangamo, it completed dosing 33 patients in the STAAR study in April and has four years of follow-up data on the longest treated patient. Additionally, the firm highlighted that all 18 patients who were on enzyme replacement therapy at the start of the trial are still off ERT after receiving the gene therapy.