In short
AAVB-039 is an investigational gene therapy being studied for Stargardt disease, a rare inherited eye condition that causes progressive sight loss. The therapy is a combination of two adeno-associated viral vectors of serotype 8 that deliver the two halves of the human ABCA4 gene. A single Phase 1/2 trial (NCT07161544) is currently authorised to assess its safety and efficacy in 75 participants.
Key points
- AAVB-039 is an investigational gene therapy, not yet an authorised medicine.
- It is being studied in Stargardt disease (STGD1), a rare inherited cause of progressive vision loss.
- The only registered trial is a Phase 1/2 study with an authorised status.
- The trial plans to enrol 75 participants across multiple centres.
- The medicine is given by subretinal injection directly into the eye.
- The trial measures safety and tolerability as its main outcome, alongside efficacy.
What is AAVB-039?
AAVB-039 is an investigational gene therapy. Its full name is the combination of two adeno-associated viral vectors of serotype 8 containing the 5'- and the 3'- half coding sequences of human ABCA4 fused to inteins. It has not received a marketing authorisation and is being studied in clinical trials.
The European Medicines Agency (EMA) granted an orphan designation for this substance on 17 October 2019, under the number EU/3/19/2208. The designation was granted to Fondazione Telethon, Italy, for the treatment of Stargardt's disease. An orphan designation is given to medicines intended for rare diseases that affect fewer than 5 in 10,000 people in the European Union.
How does AAVB-039 work?
Stargardt's disease is most often caused by abnormalities in the ABCA4 gene. This gene is responsible for producing a protein called ABCR, which regulates the transport of vitamin A byproducts in and out of certain cells in the retina, the light-sensitive surface at the back of the eye. In people with Stargardt's disease, ABCR does not work properly. As a result, deposits known as lipofuscins build up inside the retinal cells, which become damaged and eventually die.
AAVB-039 is designed to deliver a working copy of the ABCA4 gene to retinal cells. Because the ABCA4 gene is too large to fit into a single viral vector, the therapy uses two adeno-associated viral vectors of serotype 8, each carrying one half of the gene coding sequence. The two halves are fused to inteins, which are protein segments that help the two halves join together inside the cell to form a complete, functional protein.
Which conditions is it studied for?
- Stargardt disease (STGD1) — a hereditary disorder of the eye that leads to progressive loss of sight and can eventually lead to blindness. It is the most common form of inherited macular degeneration in young people.
How is AAVB-039 given?
AAVB-039 is given by subretinal injection. This means the medicine is injected directly under the retina during a surgical procedure on the eye. The trial listed in the registry describes a single administration of AAVB-039 via subretinal injection.
What do the clinical trials show?
One clinical trial of AAVB-039 is registered: an open-label, multicentre Phase 1/2 trial (NCT07161544) to assess the safety and efficacy of a subretinal administration of AAVB-039 in people with Stargardt disease. The trial is currently authorised and plans to enrol 75 participants.
The primary outcome of the trial is to measure the number and severity of treatment-related adverse events following treatment with AAVB-039. The trial also aims to determine the safety, tolerability and efficacy of a single administration of AAVB-039 via subretinal injection.
The trial is open-label, meaning both the participants and the researchers know which treatment is being given. It is a multicentre trial, conducted at more than one hospital or clinic. As a Phase 1/2 trial, it combines the early assessment of safety in humans (Phase 1) with an initial look at how well the treatment works (Phase 2).
What side effects are known?
The registered trial is designed to measure the number and severity of treatment-related adverse events, so the side effect profile of AAVB-039 is not yet fully known. The main purpose of the ongoing Phase 1/2 trial is to collect this safety information.