VG801 gene therapy shows early promise for Stargardt disease in phase 1/2 clinical trial
VeonGen has reported encouraging early results from a clinical trial of VG801, an investigational gene therapy for Startgardt disease, a genetic retinal condition that currently has no approved treatments.
VeonGen has reported encouraging early results from its ongoing phase 1/2 trial of VG801, an experimental treatment for Stargardt disease, a genetic condition that currently has no approved treatments. VG801 uses a dual viral vector approach to deliver the large ABCA4 gene in two parts to retinal cells. Early findings from a small number of participants show the treatment has been well tolerated with no serious safety concerns, alongside preliminary improvements in vision that have been sustained for up to 12 months. The therapy has also received multiple regulatory designations to support faster development, though it remains in early-stage testing and requires further rigorous research before it could become widely available.
What is Stargardt disease?
Stargardt disease is a progressive inherited retinal condition in which vision loss is caused by the death of photoreceptor cells (light-sensing cells) in the central portion of the retina called the macula. It is the most common form of juvenile macular dystrophy.
The condition is most commonly caused by mutations in the ABCA4 gene, which provides the instructions needed to make a protein found in the photoreceptor cells. This protein is responsible for transporting toxic byproducts, made by the regular visual cycle, away from photoreceptor cells. Without this protein, these toxins can accumulate over time on the macula, which we use for seeing fine detail in high definition, destroying light-sensing cells and central vision.
There are currently no treatments available for the condition, however, there are several therapeutic approaches in development, including VG801 by VeonGen.
What is VG801?
VG801 is a dual adeno-associated viral vector gene therapy. This means that a small virus, that doesn’t cause illness in humans, is used as a delivery system to introduce or alter genetic material within cells. Most gene therapies for inherited retinal diseases (IRDs) work on the premise of delivering an entire new gene to replace the mutated one, however, the whole ABCA4 gene is too large to deliver in one viral vector. VeonGen look to overcome this problem by delivering the ABCA4 gene in two halves, using dual viral vectors, through a one-time injection into the eye.
Once in the cells, each half of the gene will make half of a molecule called messenger RNA (mRNA), which tells the cell how to make the ABCA4 protein. VG801 then uses a process known as mRNA trans-splicing to bond each half of the mRNA. This complete mRNA can then be used to make a functional protein. Due to this mechanism, VG801 has the potential to treat all individuals with an ABCA4 mutation leading to Stargardt disease.
The trial:
This phase 1/2 clinical trial is the first in human trial of VG801 evaluating the preliminary efficacy, safety and tolerability of a single dose. It is a single-arm, open-label, non-randomized and single dose-escalation study. This means that both participants and researchers know who is getting which treatment dose and there is no placebo group. It also means that the dose is gradually increased across groups of participants. In early-stage clinical trials, this is common because the main focus is on safety and trying to identify the dose that is the most effective and safe.
The trial is ongoing with only one trial site in China dosing both adult and paediatric participants.
Early findings:
According to the latest press release from VeonGen, nine participants have completed a 6-month follow up and some have reached a 12-month follow-up. This early data has shown that:
- VG801 has been well tolerated, with no dose-limiting or serious adverse events reported to date.
- Preliminary efficacy data shows consistent functional improvements in best-corrected visual acuity (BCVA) and a newly developed Virtual Reality Visual Test (VRVT), with improvements sustained through six- and 12-month follow-up.
Next steps:
VG801 has been granted several Fast Track and Orphan Drug designations from various regulatory bodies which are designed to expedite the normally lengthy review process. VeonGen are reportedly continuing to work with regulatory authorities to advance VG801 toward a pivotal trial and potential accelerated regulatory submission. However, please note that these findings are from early-stage clinical trials and that more research and evidence is needed from further trials to advance VG801 toward applications for approval. Different regulatory bodies also operate in the US, UK, Europe and elsewhere, and obtaining regulatory approval can take a long time, even if VeonGen seeks to work with all of them. Reaching agreement for NHS availability is a further, separate process.
To read more about VeonGen and VG801, please visit their website here.