AAVantgarde’s Dual-Vector Gene Therapy Gains Key Regulatory Approvals for Stargardt Disease

MILAN, ITALY – October 2, 2025 – AAVantgarde Bio, a clinical-stage biotechnology company, announced two major regulatory milestones for its lead gene therapy, AAVB-039, in development for Stargardt disease. The company has been granted Orphan Drug Designation by the US Food and Drug Administration (FDA) and received Clinical Trial Authorization (CTA) approval from the UK’s Medicines and Healthcare products Regulatory Agency (MHRA).

Stargardt disease is the most common inherited form of macular degeneration, caused by mutations in the large $ABCA4$ gene. Because this gene’s 6.8-kilobase length exceeds the payload capacity of a standard adeno-associated virus (AAV) vector, AAVB-039 uses a sophisticated dual-vector gene therapy approach to deliver the full-length protein. This strategy aims to benefit patients across all $ABCA4$ mutation types.

Accelerating Development Through Regulatory Incentives

The orphan drug designation provides AAVantgarde with significant development incentives in the U.S., including tax credits, waived FDA fees, and, upon approval, seven years of market exclusivity.

Natalia Misciattelli, PhD, CEO of AAVantgarde, noted that these milestones—combined with an existing Fast Track Designation—will significantly accelerate development. “The orphan drug designation and UK CTA approval… reflect [FDA’s] and MHRA’s acknowledgement of the urgent need for treatments for patients living with Stargardt disease,” Misciattelli said.

The UK CTA approval now permits the company to proceed with clinical evaluation, aligning with earlier U.S. clearance of its Investigational New Drug (IND) application. This regulatory alignment is critical for establishing streamlined, harmonized clinical development pathways.

The advancement of AAVB-039 validates critical strategies for the biopharma industry, particularly in rare diseases where manufacturing complexity has often been a limiting factor.

By successfully developing a dual-vector system, AAVantgarde demonstrates a viable path forward for other inherited disorders requiring innovative solutions for delivering large genetic payloads. The regulatory support reduces development risk and encourages investment in scalable manufacturing platforms tailored to complex gene therapies.

AAVB-039 is currently being assessed in the Phase I/II CELESTE trial to evaluate its safety and preliminary efficacy. With an estimated 60,000 to 75,000 individuals affected by Stargardt disease across the U.S. and Europe, AAVantgarde’s progress serves as a crucial case study in reshaping rare disease drug development through technical and regulatory innovation.