SpliceBio Begins Dose-Expansion Phase of Clinical Trial for Stargardt Disease Protein Splicing Therapy

SpliceBio, a genetic medicines company developing protein splicing therapies for inherited retinal diseases, has dosed the first patient in the Part B dose-expansion portion of its Phase 1/2 ASTRA clinical trial (NCT06942572) evaluating SB-007 for the treatment of Stargardt disease caused by ABCA4 mutations. There are currently no approved therapies for Stargardt disease.

SB-007 is an investigational dual adeno-associated virus (AAV) gene therapy designed to restore expression of functional, full-length ABCA4 protein in the retina. The therapy has the potential to treat patients with all ABCA4 mutations. SpliceBio's proprietary protein splicing platform delivers two AAV vectors to overcome the size limitations of conventional AAVs, which cannot accommodate the full ABCA4 gene. Each vector carries approximately half of the ABCA4 gene; once inside retinal cells, each gene produces partial proteins that combine to make the full-length ABCA4 protein.

The first patient in Part B was treated at Oxford University Hospitals NHS Foundation Trust in Oxford, England. Robert MacLaren, MD, PhD, professor of ophthalmology at the University of Oxford, commented: “The use of two viral vectors that recombine once inside retinal cells is a unique approach to restoring the large gene needed in Stargardt disease. This unique gene therapy modality has the potential to slow or even halt the progression of this debilitating disease, which is the most common cause of inherited blindness in children.”

Part A of ASTRA evaluated three doses of SB-007 in an open-label, dose-escalation design. Part B will enroll approximately 57 patients aged 12 to 65 with Stargardt disease. In this part of the study, participants will be randomly assigned to receive one of two doses or no treatment at all (control group). Neither the patients nor the doctors will know the assignments (masking). Participants will be followed for 96 weeks. The primary goal of the study is to determine whether SB-007 is safe and tolerable. It will also examine whether SB-007 can preserve or improve vision. SB-007 is designed to be a one-time treatment administered via subretinal injection.

The FDA recently granted Fast Track designation to SB-007 after it previously received Orphan Drug designation in the US and Europe. This designation allows SpliceBio to have more frequent interactions with the FDA.

SpliceBio continues to enroll patients in its POLARIS trial (NCT06435000), a natural history study monitoring disease progression in Stargardt patients to identify appropriate patients and optimal outcome measures for clinical trials.