In the Phase 1/2 STAAR study, isaralgagene civaparvovec (ST-920) generated a positive mean annualized eGFR slope at 52 weeks across all dosed adults with Fabry disease. FDA has confirmed that eGFR slope can serve as the efficacy basis for an accelerated approval, positioning renal function trajectory—not biomarker change—as the pivotal endpoint.
The core development: FDA has accepted Sangamo’s request for a rolling submission and review of a Biologics License Application for ST-920. The company plans to begin submitting BLA modules in the fourth quarter of 2025 under the accelerated pathway. ST-920 is an AAV gene therapy administered as a single infusion without preconditioning, and the registrational evidence package will rely on the STAAR program’s safety and efficacy data, including the 52‑week renal function signal.
Strategically, this is a regulatory and operational bet on functional endpoints and on speed. Acceptance of eGFR slope as the linchpin for accelerated approval reflects FDA’s willingness to prioritize clinically interpretable organ outcomes in Fabry over lyso-Gb3 reductions, which have been widely used but variably aligned to clinical progression. For Sangamo, rolling submission allows CMC and clinical modules to advance on separate tracks, a meaningful advantage for an AAV program where analytic comparability and potency assays often gate timelines. It also indicates the company is moving ahead without a conventional randomized Phase 3, leaning on natural history, ERT-withdrawal experience, and longitudinal functional data to bridge evidentiary gaps.
The move reshapes expectations across Fabry development. Sites will need tight standardization around eGFR collection and adjudication, plus coordinated ERT tapering and discontinuation protocols, if those are part of ongoing follow-up. Long-term follow-up obligations typical of gene therapy—15 years in many programs—shift workload from infusion suites to chronic safety and durability monitoring, including immunogenicity surveillance and cardiac assessments in mixed-phenotype Fabry populations. For CROs, the center of gravity is executional rigor in renal endpoint handling, central lab harmonization, and long-horizon retention strategies. Payers and HTA bodies will focus on ERT-sparing durability, hospitalization offsets, and renal and cardiac event reduction; any outpatient, no-preconditioning profile may help operationally, but cost-effectiveness will hinge on sustained eGFR trajectories and real-world discontinuation of ERT.
The competitive and regulatory context adds tension. Several Fabry gene therapy efforts have struggled with safety signals, vector dosing, or financing, leaving room for a cleaner renal function story to carry weight—if sustained and generalizable. At the same time, eGFR slope is a noisy endpoint over short intervals, particularly in small, heterogeneous cohorts and in patients stabilized on ERT or chaperone therapy. That raises the evidentiary bar for confirmatory commitments: regulators will expect durability at 104 weeks and beyond, consistency across classic and late-onset phenotypes, and corroborating organ outcomes. CMC remains a critical risk factor; manufacturing scale, vector consistency, and clinically predictive potency assays have derailed timelines across the class.
What to watch next: the pace and completeness of CMC and clinical module submissions, any advisory committee signaling around the suitability of eGFR slope for accelerated approval, and the design of the postmarketing verification study—whether randomized against continued ERT, structured withdrawal, or a robust external control. Seroprevalence and neutralizing antibody exclusion criteria could constrain label breadth and uptake at sites, making screening logistics and alternative access pathways important. If the rolling submission proceeds smoothly and durability holds, ST-920 could test whether a functional renal endpoint can carry an AAV Fabry therapy through accelerated approval and into sustained clinical adoption; if not, expect regulators to pivot back to composite or multi-organ measures before broad endorsement.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
