Phase 3 trial begins testing one-time gene therapy for Gaucher type 1
FLT201 is being studied in adults stable on standard treatments
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The first patient has been dosed in a global clinical trial testing the safety and efficacy of FLT201 (avigbagene parvec), an investigational gene therapy that Spur Therapeutics is developing for Gaucher disease type 1.
The Phase 3 trial (NCT07223944) is recruiting up to 45 adults with Gaucher disease type 1 who have been stable on standard Gaucher treatments for at least two years at 33 locations worldwide. The company expects to complete patient enrollment within one year.
Trial may support approval filing
If positive, results from the trial are expected to be used to support an application seeking the therapy’s approval for adults with Gaucher disease type 1.
“Dosing the first patient in our Phase 3 trial is an important step forward in our efforts to redefine what is possible for individuals living with Gaucher disease,” Michael Parini, Spur’s CEO, said in a company press release. Parini said Spur is focused on advancing FLT201, which he called a “potential best-in-class, one-time treatment,” toward registration, “and the eager response from the community to participate in this trial reflects the real potential for FLT201 to address persistent unmet needs.”
Gaucher disease comprises a group of conditions caused by mutations in the GBA1 gene that result in missing or dysfunctional GCase, an enzyme that helps break down a fatty molecule called glucocerebroside, or Gb1, also known as glucosylceramide.
This leads to the toxic accumulation of Gb1 and glucosylsphingosine, a toxic metabolite also known as lyso-Gb1, which drives the disease’s symptoms. These include enlarged liver and spleen, bone issues, and blood abnormalities, such as low levels of hemoglobin — the protein that carries oxygen in red blood cells — and platelets, cell fragments that help with blood clotting.
The disease can also result in neurological symptoms, such as seizures, abnormal eye movements, and cognitive difficulties, but these are not observed in people with Gaucher type 1, the most common form.
FLT201 is a gene therapy designed to deliver a modified version of the GBA1 gene to cells in the liver, allowing them to produce a more stable version of GCase, called GCase85, with sustained activity, via a one-time infusion. The modified gene is delivered using Spur’s proprietary AAVS3 viral carrier, which is designed to target the liver, leading to GCase85 production and release.
Earlier studies showed sustained effects
Results from the Phase 1 GALILEO-1 trial (NCT05324943), which involved six adults with Gaucher type 1, and a long-term extension study, GALILEO-2 (NCT06545136), showed a favorable safety and tolerability profile with a single low-dose infusion of FLT201 at 4.5 x 10¹¹ vg/kg.
Four of the six patients were able to discontinue standard enzyme replacement therapy (ERT) or substrate reduction therapy (SRT) and remained off those therapies two years later.
These participants showed increased GCase activity, maintained or reduced lyso-Gb1 levels, improvements in hemoglobin and platelet levels or maintenance within normal ranges, stable liver and spleen volumes, and improved or maintained bone density measures. Researchers said the bone density improvements correspond to reduced fracture risk in Gaucher disease.
The Phase 3 GALILEO-3 trial is designed to further evaluate FLT201’s safety and efficacy in a larger patient population. It is evaluating FLT201 in adult patients with Gaucher disease type 1 who have been stable on ERT or SRT for at least two years.
The main goal is to assess the proportion of participants with stable hemoglobin levels at one year. Secondary outcomes include FLT201’s safety and tolerability, along with other measures of treatment efficacy, including stability of platelet counts, spleen and liver volumes, biomarker changes, bone marrow burden and mineral density changes, and patients’ quality of life.
The study is expected to end in 2032, but researchers expect to finish collecting data for its main goal by mid-2028.
“The Gaucher community is eager for further innovation that can move the standard of living care beyond chronic ERT or SRT, which not only require lifelong infusions, but also leave patients with some features of Gaucher disease that are not fully addressed by currently available treatments,” said Priya Kishnani, MD, a professor of pediatrics at Duke University and a GALILEO-3 investigator. “The GALILEO-3 trial will help further evaluate the safety and efficacy of FLT201 and its potential to improve outcomes for the patients we treat.”
