One Big Step Away From BLA Submission for Sangamo’s Fabry Gene Therapy


The FDA is allowing a small, single-arm study to support a BLA submission of ST-290, if Sangamo can find help to continue developing the therapy.

Robert Hopkin, MD, Cincinnati Children's

Robert Hopkin, MD

Credit: Cincinnati Children's

The FDA has aligned with Sangamo Therapeutics on an abbreviated pathway to approval of its gene therapy ST-920 (isaralgagene civaparvovec) for treating Fabry disease following the presentation of data demonstrating disease improvements after treatment from the phase 1/2 STAAR trial (NCT04046224).1,2

The FDA advised, in a Type D meeting, that a single study of ST-290 in 25 patients with Fabry without a control arm or head-to-head with enzyme replacement therapy (ERT), in combination with confirmatory evidence, may be an acceptable pathway to a Biologics License Application (BLA).

Sangamo is seeking a collaboration partner to advance the therapy through potential registration and commercialization. The company also announced that the European Medicines Agency (EMA) has granted priority medicines (PRIME) eligibility to the therapy.

“The US and European regulatory support for ST-920 and the serious unmet medical need in Fabry Disease signal the important role that ST-920 could play in improving the lives of Fabry patients across the globe,” Nathalie Dubois Stringfellow, PhD, Chief Development Officer, Sangamo, said in a statement.1 “We are thankful for the FDA’s support and alignment on a regulatory pathway that could potentially deliver a new treatment option for Fabry disease patients on an expedited, cost-effective timeline.

“Despite the availability of ERT and chaperone therapies, Fabry disease treatment is burdensome, with some patients still developing disease progression. To date, ST-920 has been well-tolerated, and the preliminary data showing sustained supraphysiologic α-Gal A activity and the ability to discontinue and remain off ERT are promising,” investigator Robert Hopkin, MD, Cincinnati Children’s Hospital Medical Center, said in an earlier statement.2 “The early improvements reported in disease severity, quality of life and gastrointestinal symptoms, together with evidence of reduced immunogenicity, illustrate the potential of ST-920 as a treatment option for adults with Fabry disease.”

Hopkin presented updated data from STAAR at the 2024 WORLDSymposium, held February 4-9, in San Diego, California, from 24 participants dosed. In 13 participants with at least 12 months of follow-up, Fabry outcome survey Mainz Severity Score Index improved (P = .0269), including 38% of participants on ERT. Renal function remained stable, and investigators observed statistically significant improvements on quality-of-life scores, General Health and Physical Component score, and gastrointestinal symptoms (all P <.03.).2

Furthermore, all 12 participants that discontinued ERT remain off ERT for up to 19 months as of data cut off. In 8 patients on ERT receiving the highest dose (2.63 x 1013 ), plasma lyso-Gb3 levels remained stable following ERT withdrawal for up to 1 year. Investigators also observed that total antibody (Ab) or neutralizing antibody (Nab) titers against α-Gal A decreased in all 7 participants with antibodies associated with ERT at baseline, becoming undetectable in 5 of those (71%).2 ST-290 was well-tolerated, with no liver function test (LFT) elevations requiring steroids post-treatment.

“In many of the gene therapy trials, we see inflammatory reactions that involve the liver, kidneys, heart or other organs. In this trial, we have had really very little in the way of inflammatory reactions. We see some fever, in the first day or 2, we had some reports of headaches and cold-like symptoms. But that resolves early, and then the safety has been quite stable,” Hopkin told CGTLive® about the findings.

Since the data cutoff date, the trial has dosed 4 additional participants. It has completed enrollment and the remaining participants are expected to be dosed in the first half of 2024.

“We remain encouraged by the emerging safety and efficacy data supporting the potential durable benefit that ST-920 could offer patients with Fabry disease as a convenient single-dose treatment option,” Lisa Rojkjaer, MD, Chief Medical Officer, Sangamo, added.3

“We expect to complete dosing of the remaining patients in the first half of this year as we continue to explore potential partnerships and other financing options to support the initiation of a registrational trial.”

1. Sangamo Therapeutics Announces U.S. FDA Alignment on Abbreviated Pathway to Potential Approval and EMA Prime Eligibility for ST-920 in Fabry Disease. News release. Sangamo Therapeutics. February 12, 2024.
2. Sangamo Therapeutics Announces Updated Phase 1/2 STAAR Study Data in Fabry Disease Showing Sustned Benefit and Differentiated Safety Profile. News release. Sangamo Therapeutics. February 5, 2024. 4/4
3. Hopkin RJ. Isaralgagene civaparvovec (ST-920) gene therapy in adults with Fabry disease: Updated results from an ongoing Phase 1/2 study (STAAR). Presented at: WorldSymposium; February 4-9; San Diego, California.
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