MeiraGTx’s rAAV8.hRKp.AIPL1 shows remarkable efficacy in treating severe retinal dystrophy

A gene therapy developed by MeiraGTx Holdings plc has demonstrated remarkable success in restoring vision to children born blind due to severe retinal dystrophy. The clinical-stage genetic medicines company recently announced the publication of its first-in-human interventional study in The Lancet, detailing the results of rAAV8.hRKp.AIPL1, an experimental gene therapy designed for patients with AIPL1-associated Leber congenital amaurosis 4 (LCA4).

The study highlights the efficacy of gene therapy in treating one of the most severe forms of inherited blindness, with all 11 children treated so far showing significant improvements in vision. This breakthrough underscores the potential of genetic retinal treatments to reverse early-onset blindness and could pave the way for regulatory approval and broader access to life-changing vision restoration therapies.

What Did The Lancet Study Reveal About the Effectiveness of rAAV8.hRKp.AIPL1?

The findings published in The Lancet provide compelling evidence of the transformative impact of gene therapy in treating AIPL1-related severe retinal dystrophy. The clinical study, conducted in the United Kingdom, involved two cohorts of children diagnosed with LCA4, a rare condition that leads to progressive retinal degeneration from birth.

The first group consisted of four children who received unilateral subretinal injections of rAAV8.hRKp.AIPL1. The second cohort of seven children underwent bilateral treatment, with gene therapy administered to both eyes. All 11 participants—previously diagnosed as legally blind—experienced notable improvements in visual acuity within four weeks of treatment, confirming the efficacy of gene therapy in addressing genetic retinal disorders.

The therapy works by delivering functional copies of the AIPL1 gene to the cone and rod photoreceptors in the central retina, helping to preserve retinal function and restore sight. Given that retinal dystrophy due to AIPL1 deficiency is among the most aggressive forms of congenital blindness, the results signify a major advancement in genetic retinal treatments.

What Were the Key Findings from the Clinical Study?

The study aimed to assess both safety and efficacy, and the results have been overwhelmingly positive. Prior to treatment, all children had binocular visual acuities (VA) limited to light perception. Following a single administration of rAAV8.hRKp.AIPL1, substantial improvements in visual function were observed, particularly in the treated eyes.

Comprehensive evaluations included visual acuity testing using both standard-of-care methods and an innovative touchscreen-based test. Functional vision assessments monitored the children’s visual behavior and ability to complete everyday tasks, while visual evoked potentials (VEPs) measured the brain’s response to visual stimuli, confirming restored retinal function. Retinal imaging, including optical coherence tomography (OCT) and widefield fundus imaging, demonstrated structural preservation of the retina.

The results showed that all treated children exhibited measurable visual improvements, with structural preservation evident in the treated eyes compared to the untreated ones. The improvements extended beyond visual acuity, with positive effects on developmental milestones, behavior, communication, and social interaction. Dr. Alexandria Forbes, President and CEO of MeiraGTx, described the findings as unparalleled in any previous ocular gene therapy, highlighting the exceptional clinical benefits observed in treated children.

What Is the Regulatory Path for rAAV8.hRKp.AIPL1?

Given the extraordinary clinical outcomes, MeiraGTx is now actively working with global regulators to expedite the approval process for rAAV8.hRKp.AIPL1. Following recent discussions with the UK Medicines and Healthcare products Regulatory Authority (MHRA), the company intends to submit a Marketing Authorization Application (MAA) under exceptional circumstances based on the existing data, without requiring additional clinical trials.

MeiraGTx has also initiated dialogues with the U.S. Food and Drug Administration (FDA) to explore accelerated regulatory pathways in the United States. The therapy has received orphan drug designation from both the FDA and the European Commission, as well as Rare Pediatric Disease Designation (RPDD) from the FDA, making it eligible for a Priority Review Voucher (PRV), which could be used for expedited regulatory review. Recent PRVs have sold for between $100 million and $158 million, underscoring the high demand for rare disease treatments in the biopharmaceutical industry.

What Other Gene Therapies Are in MeiraGTx’s Development Pipeline?

Beyond rAAV8.hRKp.AIPL1, MeiraGTx is advancing a broad pipeline of genetic therapies targeting inherited retinal diseases (IRDs) and other severe conditions. The company has received four Rare Pediatric Disease Designations from the FDA, including AAV8-RK-RetGC for Leber congenital amaurosis due to GUCY2D mutations (LCA1), AAV8-RK-BBS10 for Bardet-Biedl syndrome (BBS) associated with BBS10 mutations, and AAV5-RDH12, a therapy for RDH12-associated retinal dystrophy.

MeiraGTx’s vertically integrated manufacturing capabilities, which include Good Manufacturing Practice (GMP) viral vector production, allow for the efficient development and potential commercialization of these therapies. The company’s proprietary gene regulation platform further enhances the potential for wider application of genetic medicine.

What Does This Mean for the Future of Genetic Retinal Treatments?

The success of rAAV8.hRKp.AIPL1 in restoring vision in children born blind represents a landmark achievement in the field of gene therapy. If regulatory approvals move forward as anticipated, this therapy could become the first available treatment for AIPL1-related LCA4, fundamentally transforming the landscape of genetic retinal treatments.

With continued research, expanded clinical trials, and regulatory advancements, gene therapy is poised to reshape the future of precision medicine, offering lifesaving solutions for those affected by genetic blindness.