ST-920 Gene Therapy Showing Safety, Signs of Efficacy in Trial
Sangamo Therapeutics’ gene therapy candidate ST-920 safely and effectively increased and sustained the levels of the alpha-GalA protein, the enzyme that is lacking in people with Fabry disease, according to preliminary Phase 1/2 trial data.
Four people have been treated at the first two therapy doses being evaluated — 5 trillion vector genomes per kg of body weight (vg/kg) and 10 trillion vg/kg. As of the Sept. 17 data cutoff date, all showed above normal alpha-GalA activity, which has been sustained for one year in the first person treated, and for 14 weeks (about three months) in the most recently treated patient.
These findings represent an alpha-GalA activity increase between two- and 15-fold above the mean of the normal range, Sangamo reported in a press release. Based on results to date, the company has begun planning a Phase 3 clinical trial.
The Phase 1/2 study, dubbed STAAR (NCT04046224), plans to enroll up to 48 adults with Fabry in the U.S. and U.K. Contact and site information is available here.
“We are encouraged by these early yet promising results,” said Rob Schott, MD, head of development at Sangamo. “As we continue with this study, we hope to further understand the potential treatment effect over the longer-term and in more patients, while we initiate plans for a Phase 3 trial.”
In Fabry, mutations in the GLA gene lead to a faulty alpha-GalA enzyme and the buildup of fatty molecules called Gb3 and lyso-Gb3 inside cells. This accumulation causes a wide range of symptoms, and can result in life-threatening heart attacks, strokes, and kidney disease.
Enzyme replacement therapy, which provides a functioning copy of alpha-GalA to break down Gb3 and lyso-Gb3, is a standard Fabry treatment but requires lifelong infusions. Another treatment known as chaperone therapy can only help those carrying specific GLA mutations, about half of all Fabry patients.
“There is significant unmet need in Fabry disease, a progressive and challenging condition that is currently treated with frequent burdensome infusions that do not adequately address the underlying disease,” Schott said.
ST-920 is designed to deliver a healthy version of the GLA gene to the liver via a single into-the-vein infusion, which would then continuously release alpha-GalA protein into the bloodstream.
In a Fabry disease mouse model, the therapy increased alpha-GalA enzyme levels in the liver, heart, and kidneys. Mice treated at the highest dose had undetectable levels of lyso-Gb3 in all tissues and blood.
The STAAR study enrolls Fabry patients who are on ERT, those who are ERT-naïve, as well as individuals who stopped ERT for at least six months or more.
Of the four patients, ages 22 to 48, in the first dosing group, one has stopped using ERT and another is planning to stop if their alpha-GalA activity remains stable.
In addition, one patient who had high blood levels of lyso-Gb3 before treatment showed a significant drop of about 40% in these levels within 10 weeks of ST-920 infusion (about two months), which was sustained over 32 weeks (about seven months). Steady lyso-Gb3 was also maintained in those with low levels before treatment.
The treatment was generally well tolerated among the four patients. All treatment-related adverse events reported were mild with no serious events. No one had elevated liver enzymes, a sign of liver damage, that required steroid treatment.
Recently, a fifth patient was the first to be infused at a higher dose of 30 trillion vg/kg, and a sixth person is currently undergoing screening for this third dose group.
All patients will be followed for one year post-infusion to determine the therapy’s safety, and the trial is due to conclude in February 2024.
According to Sangamo, data from STAAR will be updated throughout 2022 and findings presented at a medical meeting.
ST-920 has been granted orphan drug designation in the U.S. and orphan medicinal product designation in Europe, which provides regulatory support and financial benefits to develop and potentially market the therapy. These designations are granted to treatments for life-threatening or rare chronic diseases.
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