Gene therapy keeps Gaucher patients off standard treatment for up to 2 years
Spur Therapeutics' avigbagene parvec has entered confirmatory Phase 3 trial
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Avigbagene parvec, a one-time gene therapy being developed by Spur Therapeutics for Gaucher disease type 1, helped four of six adults in a Phase 1/2 study remain off their standard treatment for up to about two years, trial data show.
While stopping treatment typically leads to a rapid increase in disease biomarkers and worsening symptoms, these patients showed improvements or stable clinical outcomes that were sustained throughout follow-up.
The findings, which come from the completed GALILEO-1 Phase 1/2 clinical trial (NCT05324943) and its ongoing long-term extension, GALILEO-2 (NCT06545136), were presented at this year’s WORLDSymposium, held Feb. 2-6 in San Diego.
The data were shared in a pair of posters and an oral presentation, titled “Two-year follow up of FLT201 AAV gene therapy in adults with Type 1 Gaucher disease: Results from GALILEO-1 and GALILEO-2,” and delivered by Ida Schwartz, MD, PhD, an investigator involved in both clinical studies.
The findings support the company’s decision to move avigbagene parvec into a confirmatory Phase 3 clinical trial (NCT07223944), which is already underway and may support both accelerated and full approval for Gaucher disease type 1.
“A single low-dose infusion of avigbagene parvec enabled patients to discontinue their prior treatments while maintaining improved or stable clinical outcomes. These results underscore the potential of gene therapy to meaningfully reshape care,” Schwartz, head of the Metabolic Clinics at Hospital de Clínicas do Porto Alegre in Brazil, said in a press release from Spur.
Avigbagene parve delivers modifies version of key gene
Gaucher disease is caused by mutations in the GBA1 gene that lead to a deficiency in glucocerebrosidase (GCase), an enzyme needed to break down certain fatty substances. Without enough functional GCase, these fatty molecules accumulate to toxic levels in various cells, leading to a range of symptoms.
The standard treatment for Gaucher disease is enzyme replacement therapy (ERT), which provides the body with a functional version of the GCase enzyme, and substrate reduction therapy (SRT), which reduces the production of fatty substances. However, these therapies require frequent dosing, and many patients still experience symptoms after years of continuous treatment.
Avigbagene parvec, formerly known as FLT201, is designed to deliver a modified version of the GBA1 gene, enabling cells to produce a more stable version of GCase that stays in circulation longer. In preclinical studies, the gene therapy led to sustained increases in GCase activity along with reductions in fatty substances.
In the GALILEO-1 trial, six adults with Gaucher disease type 1 received a single infusion of low-dose avigbagene parvec. All had been on ERT or SRT for at least two years before enrolling.
Four patients were able to discontinue their standard treatments within about 11 weeks after receiving the gene therapy, while the remaining two continued on their prior therapy. All six later enrolled in the GALILEO-2 extension study, and have been followed for a total of 20 to 29 months.
Consistent with earlier results from those four patients, avigbagene parvec led to sustained increases in GCase activity and durable reductions in blood levels of lyso-Gb1, a biomarker of disease burden. On average, lyso-Gb1 levels dropped by 83%.
As we move into the Phase 3 trial, these results reinforce our conviction in avigbagene parvec’s potential to make a meaningful and lasting difference for people with Gaucher.
Researchers also reported clearance of fat-laden cells from the bone marrow of one patient who had been on stable ERT/SRT for nine years. This is important because most patients show bone marrow involvement that does not improve despite long-term treatment.
Patient-reported outcomes, measured using the 36-Item Short Form Survey, showed improvements in pain, fatigue, and mental health after treatment.
Avigbagene parvec also led to sustained benefits in hemoglobin, the protein that carries oxygen in red blood cells, and platelets, the blood components that help blood clot. Spleen and liver volumes also remained stable.
Although two patients experienced increases in liver enzyme levels deemed related to the therapy, these resolved spontaneously or were managed with immune therapy. Infusions with the gene therapy were generally well tolerated, with no infusion-related reactions reported.
“From the outset, our goal has been to deliver a one-time gene therapy that reduces the treatment burden for people with Gaucher disease while alleviating ongoing symptoms,” said Pamela Foulds, MD, Spur’s chief medical officer. “As we move into the Phase 3 trial, these results reinforce our conviction in avigbagene parvec’s potential to make a meaningful and lasting difference for people with Gaucher.”
