Data from the ongoing Phase 1/2 STAAR clinical study of Sangamo Therapeutics' ST-920 (isaralgagene civaparvovec), an investigational gene therapy for Fabry disease, could serve as the primary evidence for its accelerated approval by the U.S. Food and Drug Administration (FDA). This eliminates the need for an additional registrational study to confirm its clinical benefit and could shorten the time for ST-920 to enter the market.
The full dataset from STAAR (NCT04046224), which is needed for the accelerated approval, will be ready in the first half of 2025, enabling Sangamo to seek a biologics license application by the second half of the year, three years earlier than expected.
Regulatory Pathway
In an earlier meeting, the FDA agreed a well-controlled registrational study, along with existing data, could be sufficient as the basis for ST-920’s approval, but it’s now providing an alternative clear regulatory pathway to accelerated approval, which grants a go-ahead based on a surrogate marker that’s thought to predict clinical benefit.
According to Sangamo's CEO, Sandy Macrae, PhD, this regulatory pathway could bring this treatment to patients significantly sooner than originally anticipated.
How ST-920 Works
Fabry disease is caused by mutations in the GLA gene, which provides instructions for producing alpha-Gal A, an enzyme that works to break down fatty molecules. When the enzyme is faulty, the molecules build up to toxic levels in cells, leading to progressive organ damage, particularly affecting the heart, kidneys, and nervous system, and resulting in a range of symptoms.
ST-920 is designed to deliver a healthy version of GLA to liver cells so they can produce a working alpha-Gal A enzyme on their own to support the breakdown of fatty molecules like Gb3 and help alleviate symptoms. It is administered as a single dose into the bloodstream.
STAAR Trial Details and Interim Results
The STAAR trial is evaluating the safety and tolerability of ST-920 in 33 men and women diagnosed with Fabry disease. Participants are followed for 52 weeks, after which they can enroll in a five-year extension study (NCT05039866). The patient with the longest follow-up has recently completed four years in the study.
Interim data indicated that ST-920 was well-tolerated, with common side effects including fever, headache, viral infection, fatigue, and cold-like symptoms. All participants demonstrated a sustained increase in alpha-Gal A enzyme levels, and their symptoms became less severe.
Notably, all 18 patients who began the study on enzyme replacement therapy (ERT) were able to discontinue ERT, while maintaining alpha-Gal A levels at normal or above-normal. Furthermore, in the 18 patients with more than one year of follow-up, ST-920 led to significant improvements in eGFR, suggesting enhanced kidney function. Based on these data, the FDA agreed that the eGFR slope at 52 weeks could serve as a primary basis for approval. The FDA also suggested calculating the eGFR slope at 104 weeks to confirm long-term benefit.
Regulatory Designations
Sangamo was awarded fast track status for ST-920 last year, facilitating more frequent engagement with the FDA. ST-920 also holds orphan drug and regenerative medicine advanced therapy designations in the U.S., as well as orphan medicinal product designation and priority medicines eligibility in the European Union.
