AAVantgarde’s Stargardt Gene Therapy AAVB-039 Garners FDA Fast Track Designation

AAVantgarde Bio’s AAVB-039, an investigational adeno-associated virus (AAV) vector-based gene therapy intended to treat Stargardt disease, has received fast track designation from the FDA.¹

AAVB-039 is intended to deliver a functional copy of the disease-targeted ABCA4 gene. The gene therapy product utilizes a dual AAV vector, as ABCA4 is too large to be transported by a standard AAV vector.

“We are thrilled that the FDA has granted fast track designation for AAVB-039, as it 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,” Natalia Misciattelli, PhD, the chief executive officer of AAVantgarde, said in a statement.¹ “This designation represents an important milestone for our program and enables us to accelerate development efforts as we work to bring a potentially transformative therapy to patients as quickly as possible.”

Notably, AAVB-039 received clearance of an investigational new drug (IND) application from the FDA in July 2025.² At the time of the IND clearance, AAVantgarde stated that it would be initiating a first-in-human, phase 1/2 clinical trial (CELESTE, NCT identifier pending). CELESTE will take place in the United States. A separate prospective natural history study, referred to as STELLA (NCT06591806) is also being carried out by AAVantgarde in the US, United Kingdom, and Europe, and has informed the design of CELESTE, along with providing additional information about Stargardt disease’s characterization.

“The IND clearance for AAVB-039 is a testament to the scientific foundation and translational potential of our proprietary dual AAV intein platform,” Alberto Auricchio, PhD, the chief scientific officer and scientific founder of AAVantgarde, said in a July 2025 statement.² “Delivering large genes like ABCA4 has been a challenge in the field. Our approach, validated by rigorous preclinical studies showing quantified high transduction, expression, and long-term safety in multiple relevant models offers a potential therapeutic that addresses the genetic root cause for patients with Stargardt disease.”

In addition to AAV-039, AAVanatgarde is also developing AAVB-039, (also known as AAV8.MYO7A), an investigationalAAV vector-based gene therapy intended to treat retinitis pigmentosa associated with Usher syndrome type 1B (USH1B).³ AAVB-081 is a dual hybrid product comprised of 2 AAV8 vectors that is intended to provide a functional copy of the disease-targeted gene, Myo7A, which is too large to be carried in a single AAV vector. The gene therapy product is administered to patients subretinally.

Notably, in September 2024, AAVanatgarde announced the dosing of the first patient in the phase 1/2 LUCE-1 clinical trial (NCT06591793), a first-in-human clinical trial evaluating AAVB-081. The multicenter, open-label LUCE-1 trial takes the form of a dose escalation study and is expected to enroll 15 patients in total. Open to patients with USH1B who are aged 18 to 50 years old, the trial is recruiting at locations in London, in the UK, and Naples, Italy.

“I am delighted to be involved as principal investigator in this first-in-human phase 1/2 clinical study of AAV-081 for patients with retinitis pigmentosa related to USH1B,” Francesca Simonelli, the head of the Ophthalmology Unit at the University Hospital of Campania Luigi Vanvitelli, said in a September 2024 statement.³ “Through this innovative program, we aim to revolutionize our approach to understanding and treating these underserved patients. We are poised to generate robust evidence that will not only advance scientific knowledge, but also directly impact patient care.”

REFERENCES
1. AAvantgarde Bio announces FDA fast track designation for AAVB-039 for the treatment of Stargardt disease. News release. AAVantgarde Bio. August 12, 2025. Accessed August 12, 2025. https://www.aavantgarde.com/en/news/aavantgarde-bio-announces-fda-fast-track-designation-for-aavb-039-for-the-treatment-of-stargardt-disease/
2. AAVantgarde receives FDA IND clearance to progress stargardt disease program AAVB-039. News release. AAVantgarde Bio. July 15, 2025. Accessed August 12, 2025. https://www.aavantgarde.com/en/news/aavantgarde-receives-fda-ind-clearance-to-progress-stargardt-disease-program-aavb-039/
3. AAVantgarde announces first patient dosed with AAVB-081 in FIH Phase 1/2 LUCE-1 study for retinitis pigmentosa related to USH1B. News release. AAVantgarde Bio. September 16, 2024. Accessed August 12, 2025. https://www.aavantgarde.com/en/news/aavantgarde-announces-first-patient-dosed-with-aavb-081-in-fih-phase-12-luce-1-study-for-retinitis-pigmentosa-related-to-ush1b/