Barcelona-based SpliceBio is advancing a novel gene therapy, SB-007, for Stargardt disease, a leading cause of inherited juvenile macular degeneration. The company has begun the dose-expansion phase of its Phase 1/2 ASTRA trial, evaluating the treatment’s safety and tolerability in patients with the rare retinal condition [1]. This step marks significant progress toward a potential therapy for a disease that currently has limited treatment options, and builds on SpliceBio’s pioneering work utilizing a unique protein splicing approach to gene therapy [2].
Barcelona-based gene therapy company SpliceBio has initiated the dose-expansion phase of its Phase 1/2 ASTRA clinical trial evaluating SB-007, a potential treatment for Stargardt disease, a rare inherited retinal condition. The move marks a significant step forward in the development of a therapy for a disease with limited treatment options, and highlights the growing potential of gene therapies in ophthalmology.
The company announced that the first patient has been treated with SB-007 at an Oxford, UK, clinical site as part of the ASTRA trial. SpliceBio is pioneering therapies based on protein splicing, a novel approach to gene therapy.
The ASTRA trial is expected to continue through late 2028. The primary goal of the study is to assess the safety and tolerability of SB-007 in individuals diagnosed with Stargardt disease, a genetic disorder that causes progressive loss of central vision and can lead to severe visual impairment.
“Gene therapy holds substantial promise in the field of ophthalmology,” said Aniz Girach, Chief Medical Officer of SpliceBio. “Its application has been limited by the challenges of delivering large genes like ABCA4. SB-007 is designed to enable the reconstitution of the full therapeutic protein in the retina.”
Targeting the ABCA4 Gene
Stargardt disease is caused by mutations in both copies of the ABCA4 gene, which provides instructions for making a protein crucial for the function of retinal photoreceptors. These mutations lead to a buildup of toxic byproducts and progressive vision deterioration.
SB-007 is a gene therapy engineered to restore the expression of a complete and functional ABCA4 protein. The therapy utilizes two adeno-associated virus (AAV) vectors to overcome the historical limitation of the ABCA4 gene’s size, which is too large to fit into a single conventional AAV vector.
Once inside retinal cells, the two gene fragments recombine through the protein splicing technology. This process aims to produce a fully functional ABCA4 protein. The company believes this approach could be applicable to patients with various mutations in the ABCA4 gene.
About the ASTRA Clinical Trial
The ASTRA trial is a randomized, controlled, and masked study involving individuals aged between 12 and 65 years with a confirmed diagnosis of Stargardt disease.
Phase B of the trial will compare two dosage levels of SB-007 against a control group receiving no treatment. Participants will be monitored for 96 weeks. The primary endpoint is to evaluate the safety and tolerability of the treatment, with a focus on ocular and non-ocular adverse events. Secondary endpoints will assess various visual efficacy measures and structural changes in the retina.
Approximately 57 participants are expected to enroll in the study. Detailed information about the trial is available on ClinicalTrials.gov, under identifier NCT06942572.
Regulatory Status and Additional Studies
SB-007 has received Fast Track designation from the U.S. Food and Drug Administration (FDA). It previously secured orphan drug designation in both the United States and the European Union. These designations are designed to accelerate the development of treatments for rare and serious diseases with limited therapeutic options.
In parallel, the POLARIS study, a natural history study of individuals with Stargardt disease, is ongoing. This study aims to improve understanding of the disease’s progression and support the interpretation of future clinical trials.
🔗 Original SpliceBio News Release:
SpliceBio Initiates Dose-Expansion Portion of Phase 1/2 ASTRA Clinical Trial for SB-007, a Dual-AAV Gene Therapy for Stargardt Disease
https://splice.bio/splicebio-initiates-dose-expansion-portion-of-phase-1-2-astra-for-sb-007/
Article drafted with AI assistance for document analysis, synthesis, and writing.
