The US Food and Drug Administration has selected Abeona Therapeutics' ABO-503 gene therapy for X-linked retinoschisis (XLRS) to participate in its Rare Disease Endpoint Advancement (RDEA) Pilot Program, marking a significant milestone for the development of treatments for this rare inherited retinal disease.
Enhanced FDA Collaboration for Rare Disease Development
As part of the RDEA program, Abeona will have opportunities for enhanced communication and collaboration with the FDA, including frequent advice and regular ad-hoc conversations to accelerate the development and validation of product-specific novel efficacy endpoints for the company's XLRS program.
"We are honored that ABO-503 gene therapy for XLRS has been chosen for the FDA's highly competitive RDEA pilot program," said Vish Seshadri, CEO of Abeona. "We believe our participation will meaningfully improve the success rate of our XLRS clinical development efforts and, more broadly, could help facilitate pipeline innovation by using novel efficacy endpoints in new therapy development across other inherited retinal diseases."
Understanding the RDEA Pilot Program
The FDA launched the RDEA Pilot Program to support the development of novel efficacy endpoints for rare disease treatments. Under the pilot program, between 2023 and 2027, the FDA will accept up to one RDEA proposal per quarter with a maximum of three proposals per year. To be considered, sponsors must submit a proposal detailing the data they plan to collect, the novelty of the endpoint, and its potential to establish substantial evidence of effectiveness.
An additional goal of the program is promoting "innovation and evolving science" by sharing learnings on novel endpoint development through FDA presentations, guidance documents, public workshops, and a public-facing website.
ABO-503 Preclinical Efficacy Data
ABO-503 is composed of a functional human RS1 gene packaged in the novel AIM capsid AAV204. The gene therapy has shown preclinical efficacy following delivery to the retina in a mouse model of XLRS. Preclinical studies have demonstrated structural and functional improvements following robust RS1 expression throughout the retina, including improved cone photoreceptor density and overall photoreceptor cell survival, restoration of outer retina architecture by eliminating cysts characteristic of XLRS, and improvements in visual function as demonstrated by electroretinogram (ERG).
Abeona anticipates completing IND-enabling studies in the second half of 2026.
Addressing Significant Unmet Medical Need
XLRS is a rare, monogenic retinal disease that results in the irreversible loss of photoreceptor cells and severe visual impairment. The disease is caused by mutations in the RS1 protein, which is normally secreted by retinal photoreceptors and bipolar neurons and functions to mediate cell-cell adhesion. XLRS is characterized by abnormal splitting of the layers of the retina, resulting in poor visual acuity, which can progress to legal blindness.
The incidence of XLRS is estimated to be between 1 in 5,000 and 1 in 20,000 in males, with an estimated prevalence of 35,000 in the United States and Europe combined. There are currently no disease modifying therapies approved for XLRS, but because the genetics of the disease are well understood, early intervention via gene therapy has significant potential to reverse or stabilize disease progression at early stages and prevent vision loss.
"XLRS is an underserved area with a large unmet need," Seshadri noted.
Strategic Partnerships and Technology Platform
Recently, Beacon Therapeutics exercised its option agreement to license Abeona Therapeutics' patented AAV204 capsid for use in potential gene therapies for a range of prevalent and rare retinal diseases that result in blindness. This worldwide, non-exclusive license is pursuant to the agreement between Abeona and Beacon that was announced in July 2024 to evaluate the therapeutic potential of AAV204.
