Preclinical evaluation of AL-001, a gene therapy for wet age-related macular degeneration.

Suprachoroidal delivery of AL-001 achieves sustained aflibercept expression and superior efficacy with minimal inflammation in a nonhuman primate model of wet age-related macular degeneration.

• Why it matters: Effective management of wet AMD requires frequent intravitreal injections, which pose safety and compliance challenges. Developing a long-lasting, targeted gene therapy could significantly improve patient outcomes and reduce treatment burden.
• What they did: The study developed and characterized AL-001, an engineered rAAV vector expressing aflibercept, and evaluated its expression, efficacy, and safety via suprachoroidal and intravitreal routes in rabbits and nonhuman primates, with a focus on lesion reduction and pharmacokinetics.
• The result: A single suprachoroidal injection of AL-001 provided durable antiangiogenic effects, reduced lesion incidence to 0%, and showed favorable safety with only mild inflammation, supporting its potential as a long-acting therapy for wet AMD.