Updated Data Suggests Sangamo’s Gene Therapy ST-920 Improves Renal Function in Fabry Disease

Data from Sangamo Therapeutics’ phase 1/2 STAAR clinical trial (NCT04046224) evaluating isaralgagene civaparvove (ST-920), an investigational adeno-associated virus vector-based gene therapy product intended to treat Fabry disease, indicate improvements in renal function.¹ The updated results were presented at the 21st Annual WORLDSymposium, held February 3 to 7, 2025, in San Diego, California.

Among the 23 patients in the trial who had reached at least 12 months of posttreatment follow-up, a positive mean annualized eGFR slope of 3.061 mL/min/1.73m2/year (95% confidence interval: 0.863, 5.258) was reported. According to Sangamo, this implies noteworthy improvement to kidney function. In addition, 15 of the 23 patients showed improvement in total Mainz Severity Score Index (MSSI) score and 7 of the 23 patients showed improvement in their disease category on the Fabry Outcome Survey adaptation of the MSSI. Furthermore, a mean 10.6 change in General Health score (P = .0020) on the short form-36 (SF-36) quality of life (QoL) survey was reported in this group. SF-36 scores for physical component, bodily pain, physical, vitality, social function, and emotional also showed significant improvement. On the gastrointestinal symptom rating scale, statistically significant improvements from baseline were observed, as well.

Sangamo reported additional findings for the larger group of patients who were dosed in STAAR and had any amount of follow-up. The company noted that in the longest treated patient in the trial, an elevated expression of alpha-galactosidase A (α-Gal A) activity was sustained for 47 months. For the longest treated patient who received 2.63x10¹³ vg/kg of ST-920, which constituted the highest dose level, an elevated expression of α-Gal A activity was sustained for 27 months. Notably, all patients (n=18) who entered the trial while taking standard of care enzyme replacement therapy (ERT) withdrew from ERT in the posttreatment period, with none having resumed ERT at a later date. In these patients, Sangamo pointed out that stable levels of plasma lyso-Gb3 were maintained postwithdrawal, with the longest treated patient in this group having reached 33 months of follow-up after withdrawal. The company also stated that for the 10 patients who at baseline had measurable titers of total antibodies (Ab) or neutralizing antibodies (Nab) against α-Gal A associated with ERT, amarked posttreatment reduction in total Ab or NAb titers was seen in 9 patients. Furthermore, in 7 of these patients, the total Ab or NAb titers reached undetectable levels in the posttreatment period.

With regard to safety, Sangamo characterized ST-920 as “generally well-tolerated". Most adverse events (AEs) in the study were assessed as grade 1 or grade 2 in severity, and there were no AEs that resulted in patients withdrawing from participation. The company noted that there no cases of steroids being necessary to manage liver function testelevations after treatment. No deaths occurredonstudy.

“These updated data from the Phase 1/2 STAAR study are highly encouraging, particularly the positive mean eGFR slope observed in patients with at least 1 year of follow-up, indicating improvements in renal function, an important predicter of morbidity and mortality in Fabry disease,” STAAR investigator Derralynn Hughes, MA, Dphil, FRCP, FRCPath, Royal Free London NHS Foundation Trust, said in a statement.¹ “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. These data support the potential of ST-920 to be a single-dose, durable treatment option for people living with Fabry disease.”

In October 2024, Sangamo emerged from a Type B interaction with the FDA having come into alignment with the agency on plans to pursue an accelerated approval pathway for ST-920.² The company noted that based on the interaction it intends to use 1 year posttreatment eGFR slope data from all patients treated in STAAR, which has completed enrollment and dosing, as an intermediate clinical end point for a planned biologics license application (BLA), which the company expects to submit in the second half of 2025.^1,2 The company noted that it anticipates reporting the complete data set that will support the BLA later in the first half of this year.

CGTLive® has previously spoken with Robert J. Hopkin, MD, associate professor, clinical pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, to learn more about ST-290 and future research for Fabry disease. In a 2024 interview, Hopkin discussed other investigations into novel therapies for Fabry, including ex vivo gene-edited cell therapy, and further research looking deeper into the biology of the disease itself.

“We know that the stored material causes problems,” Hopkin told CGTLive. “But one of the questions that we haven't understood very well is how does that cause problems? And we know that some of it is just the presence of this substance that builds up. But there's growing evidence that that the presence of distorted material causes distress to the cells, which leads to inflammation, as the body's defenses ramp up to protect the tissues. And there's now emerging data on how that works. And we're hoping that we will be able to find which biomarkers of inflammation are initiating that inflammatory response."

REFERENCES
1. Sangamo Therapeutics announces updated phase 1/2 STAAR study data in Fabry disease showing sustained benefit, improvements in kidney function and favorable safety profile. News release. February 6, 2025. Accessed February 6, 2025. https://investor.sangamo.com/news-releases/news-release-details/sangamo-therapeutics-announces-updated-phase-12-staar-study-0
2. Sangamo Therapeutics announces alignment with FDA on accelerated approval pathway for ST-920 in Fabry disease with BLA submission expected in 2025. News release. Sangamo Therapeutics, Inc. October 22, 2024. Accessed February 6, 2025. https://investor.sangamo.com/news-releases/news-release-details/sangamo-therapeutics-announces-alignment-fda-accelerated