New Data Supports Fabry Disease Treatment

These data were presented at the 21^st Annual WORLDSymposium in San Diego, CA on February 6, 2025, and will also be available on Sangamo’s website on the Presentations page.

“These updated data from the Phase I/II STAAR study are highly encouraging, particularly the positive mean eGFR slope observed in patients with at least one year of follow-up, indicating improvements in renal function, an important predicter of morbidity and mortality in Fabry disease. Additionally, these data show the strong safety and sustained benefit profiles of ST 920, as well as its ability to improve key quality of life measures,” said Professor Derralynn Hughes, MA Dphil FRCP FRCPath, Royal Free London NHS Foundation Trust and investigator of the Phase I/II STAAR study. “These data support the potential of ST 920 to be a single-dose, durable treatment option for people living with Fabry disease.”

“Following our alignment with the FDA on an Accelerated Approval Pathway for ST 920, we are thrilled with how the data are progressing, particularly the positive one-year mean eGFR slope data that will serve as the primary efficacy endpoint for our regulatory submission,” said Nathalie Dubois-Stringfellow, Ph. D, Chief Development Officer at Sangamo. “We look forward to building upon the STAAR study’s positive results as we advance our interactions with the FDA ahead of the potential BLA submission in the second half of 2025 and we also continue to engage with the European Medicines Agency.”

Updated Phase 1/II STAAR Study Results (as of the September 12, 2024 cut-off date)

1. Safety (all dosed patients): i) Isaralgagene civaparvovec continued to be generally well-tolerated, with the majority of adverse events being grade 1-2 in nature. ii) No liver function test (LFT) elevations post-dosing requiring steroids occurred. No adverse events led to study discontinuation and there were no deaths. 

2. Efficacy (all dosed patients): i) Elevated expression of α-Gal A activity maintained for up to 47 months for the longest treated patient, and up to 27 months for the longest treated patient receiving the highest dose (2.63x10¹³ vg/kg). ii) All 18 patients who began the study on ERT have been withdrawn from ERT and all remain off ERT as of today. Plasma lyso-Gb3 levels in these patients remained stable following ERT withdrawal for up to 33 months for the longest treated patient. iii) Of the 10 patients who had measurable titers of total antibodies (Ab) or neutralizing antibodies (Nab) against α-Gal A associated with ERT at baseline, total Ab or NAb titers decreased markedly in nine patients and became undetectable in seven following ST 920 treatment. 

3. Efficacy (23 dosed patients followed for at least 12 months): i) A positive mean annualized eGFR slope of 3.061 mL/min/1.73m²/year (95% confidence interval: 0.863, 5.258) was observed, indicating notable improvements in kidney function. ii) Improvements in disease severity were reported in the Fabry Outcome Survey adaptation of the Mainz Severity Score Index (FOS-MSSI) age-adjusted score, with 15 patients showing improvements in their total MSSI score and seven patients improving their FOS-MSSI disease category. iii) Significant improvements continued to be observed in the short form-36 (SF-36) quality of life (QoL) scores reported, with a mean change in General Health score of 10.6 (p=0.0020). For context, a three- to five-point change on any SF-36 score is considered a minimally clinically important difference. iv) Significant improvements in physical component, bodily pain, physical, vitality, social function, and emotional SF-36 scores were also observed. v) Statistically significant improvements continued to be seen in the gastrointestinal symptom rating scale (GSRS) compared to baseline. vi) Collectively, Sangamo believes these data continue to support the potential for isaralgagene civaparvovec as a one-time, durable treatment for Fabry disease that can improve patient outcomes.

Enrollment and dosing are complete in the Phase I/II STAAR study. In October 2024, Sangamo announced that the FDA had provided a clear regulatory pathway to Accelerated Approval for isaralgagene civaparvovec using data from ongoing Phase I/II STAAR study, avoiding the requirement for an additional registrational study and accelerating estimated time to potential approval by approximately three years. The FDA agreed in a Type B interaction that data from the ongoing Phase /III STAAR study can serve as the primary basis for approval under the Accelerated Approval Program, using eGFR slope at 52 weeks across all patients as an intermediate clinical endpoint.

The 52-week eGFR slope data from all enrolled patients in the Phase I/II STAAR study will be available in the first half of 2025. A potential BLA submission is anticipated in the second half of 2025. Sangamo continues to advance business development discussions regarding a potential ST 920 collaboration agreement.

A Current Report on Form 8-K summarizing the updated preliminary results from the Phase I/II STAAR study in more detail will be filed by Sangamo, and this press release is subject to the further detail provided in that Form 8-K.

About the STAAR Study

The Phase I/II STAAR study is a global open-label, single-dose, dose-ranging, multicenter clinical study designed to evaluate isaralgagene civaparvovec, or ST 920, a gene therapy product candidate in patients with Fabry disease. Isaralgagene civaparvovec requires a one-time infusion without preconditioning. The STAAR study enrolled patients who are on ERT, are ERT pseudo-naïve (defined as having been off ERT for six or more months), or who are ERT-naïve. The FDA has granted Orphan Drug, Fast Track and RMAT designations to isaralgagene civaparvovec, which has also received Orphan Medicinal Product designation and PRIME eligibility from the European Medicines Agency and Innovative Licensing and Access Pathway from U.K. Medicines and Healthcare products Regulatory Agency.