AAVantgarde’s Stargardt Gene Therapy AAVB-039 Garners FDA Orphan Drug Designation, Cleared for Trial in UK

AAVantgarde Bio’s AAVB-039, an investigational adeno-associated virus (AAV) vector-based gene therapy intended to treat Stargardt disease, has received orphan drug designation (ODD) from the FDA and clearance of a clinical trial application (CTA) from the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA).¹

AAVB-039, which is currently being evaluated in the first-in-human, phase 1/2 CELESTE clinical trial (NCT07161544) in the United States, 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. The therapy previously received FDA fast track designation in August 2025.²

“The ODD and UK CTA approval represent 2 important regulatory milestones for AAVB-039 and reflect the FDA’s and MHRA’s acknowledgement of the urgent need for treatments for patients living with Stargardt disease,” Natalia Misciattelli, PhD, the chief executive officer of AAVantgarde, said in a statement.¹ “With fast track designation already in place, we now have a suite of regulatory incentives that will help accelerate development and bring this potentially transformative therapy to patients and families as efficiently as possible.”

The investigational new drug (IND) application enabling the launch of CELESTE in the US was cleared by the FDA in July 2025.³ A separate prospective natural history study, referred to as STELLA (NCT06591806) is also being carried out by AAVantgarde in the US, UK, 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.³ “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.”

AAVB-039 is not the only gene therapy product currently in development for Stargardt disease. Notably, Ocugen’s OCU410ST, an investigational AAV vector-based gene therapy, is currently being evaluated in the phase 2/3 GARDian3 clinical trial (NCT05956626) for Stargardt disease.⁴ The first patient was dosed in GARDian3 in July 2025.⁵ The phase 2/3 trial will enroll 51 participants with Stargardt disease, and 34 of the patients will be treated with a 1-time subretinal injection of OCU410ST (200 μL at a concentration of 1.5 × 10¹¹ vector genomes/mL) in their worse-seeing eye, whereas 17 participants will act as untreated controls. In August 2025, Ocugen announced that the European Medicines Agency Committee for Medicinal Products for Human Use had provided Ocugen with a positive opinion regarding the use of data from the United States–based GARDian3 trial to support a marketing authorization application for OCU410ST.⁴

“This positive opinion endorses a single trial as the basis for both biologics license application [BLA] and MAA submissions and brings us closer to providing a 1-time, modifier gene therapy to approximately 100,000 Stargardt patients in the US and Europe combined,” Shankar Musunuri, PhD, the chairman, chief executive officer, and cofounder of Ocugen, said in an August 2025 statement.⁴ “We are very encouraged about the prospect of addressing the unmet medical need that exists for these patients who currently have no approved treatment options available to them.”

REFERENCES
1. AAVantgarde announces FDA orphan drug designation and UK CTA approval for AAVB-039 for the treatment of Stargardt disease. News release. AAVantgarde Bio. October 2, 2025. Accessed October 21, 2025. https://firstwordpharma.com/story/6230309
2. 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/
3. AAVantgarde receives FDA IND clearance to progressstargardt 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/
4. Ocugen, Inc. announces positive scientific advice from the European Medicines Agency related to the approval pathway for OCU410ST—modifier gene therapy for Stargardt disease. News release. Ocugen Inc. August 13, 2025. Accessed August 14, 2025. https://ir.ocugen.com/news-releases/news-release-details/ocugen-inc-announces-positive-scientific-advice-european-0
5. Ocugen, Inc. announces first patient dosed in phase 2/3 GARDian3 pivotal confirmatory trial for OCU410st—novel modifier gene therapy candidate for Stargardt disease. News release. July 18, 2025. Accessed August 14, 2025. https://ir.ocugen.com/news-releases/news-release-details/ocugen-inc-announces-first-patient-dosed-phase-23-gardian3