AAVantgarde Bio has received Fast Track designation from the FDA for AAVB-039, an investigational gene therapy under clinical development for the treatment of Stargardt disease.
The announcement follows last month’s news of the federal agency greenlighting AAVantgarde’s investigational new drug (IND) application for a phase 1/2 trial on the same asset.
First: Tell me about this designation.
Fast Track designation is part of an FDA program for investigational drugs that also includes Regenerative Medicine Advanced Therapy (RMAT) and Breakthrough designations (BTD).
Who it’s issued to: Companies looking to expedite the development and regulatory review process of an investigational therapeutic with the intended purpose of treating serious medical conditions and filling an unmet need.
- A major bonus: Non-clinical data and/or preliminary clinical evidence aren’t required in a company’s submission request for Fast Track.
Nice! And Stargardt fits the disease criteria, right?
Indeed it does. Not only is it one of the most common inherited single-gene retinal diseases, but there are also no treatments yet approved.
Some background: Stargardt is caused by changes (mutations, to be more accurate) in the ATP-binding cassette subfamily A, member 4 (ABCA4) gene.
- Note: This gene affects how the body uses Vitamin A, and follows an autosomal recessive pattern of inheritance.
As such: These mutations lead to defective processing in the ABCA4 gene and the buildup of Vitamin A byproducts in and around the macula—resulting in damage to retinal pigmental epithelium (RPE) cells that eventually lead to cell death, causing vision loss.
Alrighty, now let's talk about this candidate.
AAVB-039 is part of AAVantgarde’s adeno-associated virus (AAV) gene therapy pipeline.
More specifically: The therapeutic is an intra-retinal AAV8 (AAV serotype 8)-intein-mediated product that targets the critical ABCA4 gene.
- And a quick reminder: AAV8 is a specific viral vector type that delivers genetic material to the retina (targeting photoreceptor cells) to treat retinal disease (such as Stargardt).
Back to AAVB-039: It uses AAVantgarde’s proprietary dual AAV intein platform to deliver the full-length ABCA4-protein and address the root cause of Stargardt, enabling treatment for all Stargardt patients (regardless of the specific mutation).
- To note: Delivery of large genes like ABCA4 has, historically, been a major challenge for retinal diseases—and AAVB-039 addresses this.
Nice! But what is this dual AAV intein platform, exactly?
This platform is one of two developed by AAVantgarde and designed to address the aforementioned capacity limitation associated with AAV vectors’ DNA cargos.
- Focusing on AAV intein, the platform is based on protein trans-splicing with one major disease target: Stargardt.
And what’s included in it?
Two AAV vectors, each with an independent expression cassette encoding one of a target protein’s two halves, accompanied by short sequences (split iteins).
- Click here for a rundown on how it works (hint: the process involves a subretinal injection).
Take note: As we mentioned, the intended resulting effect is protein trans-splicing and full-length protein reconstitution in the retina.
Got it. Now circle back to this designation … what does it mean for AAVB-039?
As with any FDA-granted designation, Fast Track comes with several advantages.
Among them: More frequent meetings and communications with the FDA to discuss:
- Development plans (such as proposed clinical trial designs and biomarker use)
- Potential eligibility for accelerated approval and priority review (if criteria are met)
- Rolling review of a future new drug application (NDA)
- Enabling an NDA submission in stages rather than waiting until all sections are completed (as per standard, non-expedited practice)
Any feedback from the company?
Notably, from CEO Natalia Misciattelli, PhD.
She emphasized that Fast Track designation “underscores the urgent unmet need and important potential of our program due to the serious nature of challenges faced by patients living with Stargardt disease.”
Speaking of clinical trial designs, there’s one already in the works, right?
Planning for it is, at least. And yes! This would be the study we mentioned earlier (which AAVantgarde was granted FDA clearance for): CELESTE, a U.S.-based, multicenter, open-label, dose-escalation first-in-human (FIH) phase 1/2a study.
What we know so far: The trial is evaluating the safety, tolerability, and preliminary efficacy of AAVB-039 when administered via sub-retinal injection among Stargardt patients.
- To note: No specific timeframe for clinical data has been established as of yet.
Any other studies to be aware of?
One other ongoing trial: STELLA, a prospective natural history trial (NCT06591806) underway across the U.S., Europe, and the United Kingdom.
Stay tuned between now and 2027 (its estimated end date) for clinical data!