Sangamo Therapeutics has reached an agreement with the FDA for an accelerated approval pathway for isaralgagene civaparvovec (ST-920), a gene therapy targeting Fabry disease. This decision is based on positive data from the ongoing Phase 1/2 STAAR clinical trial (NCT04046224), potentially bringing the therapy to market three years ahead of schedule.
The FDA has agreed that the 52-week estimated glomerular filtration rate (eGFR) slope data from the STAAR trial can serve as an intermediate clinical endpoint for a Biologics License Application (BLA) under the Accelerated Approval Program. Sangamo anticipates submitting the BLA in the second half of 2025, with the complete data set supporting the application expected in the first half of the same year.
Promising Data from STAAR Trial
The STAAR trial has demonstrated encouraging results, with data from 18 patients treated with ST-920 showing statistically significant improvements in both mean and median eGFR levels, resulting in a positive annualized eGFR slope. The FDA has indicated that the eGFR slope at 104 weeks may be used to confirm clinical benefit.
Earlier data presented at the 2024 WORLD Symposium by investigator Robert Hopkin, MD, from Cincinnati Children’s Hospital Medical Center, highlighted improvements in Fabry Outcome Survey Mainz Severity Score Index (P = 0.0269) in 13 participants with at least 12 months of follow-up. Renal function remained stable, and statistically significant improvements were observed in quality-of-life scores and gastrointestinal symptoms (all P < 0.03).
Addressing Unmet Needs in Fabry Disease
Fabry disease, an X-linked lysosomal storage disorder, leads to the accumulation of globotriaosylceramide (Gb3) in cells, causing damage to vital organs. Current treatments, such as enzyme replacement therapy (ERT), require frequent infusions and only partially address the disease's manifestations.
Sandy Macrae, MB, ChB, PhD, CEO of Sangamo, emphasized the potential of ST-920 to alleviate many manifestations of Fabry disease, stating, “I strongly believe in the potential for ST-920 to alleviate many manifestations of Fabry disease and am delighted to have a clear regulatory pathway that could bring this treatment to patients significantly sooner than originally anticipated.”
STAAR Study Details
The Phase 1/2 STAAR study is an open-label, single-dose, dose-ranging, multicenter trial evaluating the safety and tolerability of ST-920 in Fabry disease patients. The study includes patients on ERT, ERT pseudo-naïve, and ERT-naïve individuals. ST-920 has been granted Orphan Drug, Fast Track, and RMAT designations by the FDA, as well as Orphan Medicinal Product designation and PRIME eligibility from the EMA and Innovative Licensing and Access Pathway from the U.K. Medicines and Healthcare products Regulatory Agency.
Dosing in the STAAR study was completed in April 2024, with 33 patients dosed. The final patient who started on ERT was successfully withdrawn in September 2024, and all 18 patients remain off ERT. The 52-week eGFR slope data from all enrolled patients will be available in the first half of 2025.
