Our mission at REGENXBIO is to improve lives through the curative potential of gene therapy. We have made tremendous strides with our NAV technology since the first adeno-associated virus (AAV) vectors were identified in the 1960s. When Novartis received US FDA approval of Zolgensma (onasemnogene abeparvovec-xioi), a one-time gene therapy for spinal muscular atrophy in children, in May 2019 — a therapy using our own proprietary NAV AAV9 vector — I was elated and humbled. It signified that REGENXBIO’s decade-long focus on developing AAV-based gene therapy not only had advanced science in a meaningful way, but also had helped bring a transformational treatment to children and their families affected by a devastating condition.

Retina has the distinction of being the field in which the first gene therapy was approved by the FDA: Luxturna (voretigene neparvovec-rzyl; Spark Therapeutics) was approved in December 2017 as a one-time treatment for biallelic RPE65 mutation-associated retinal dystrophy. My personal interest in developing gene therapy for the eye came from an early publication of research related to Luxturna in the New England Journal of Medicine in 2013. What struck me at the time of that publication was that the researchers showed that by directly targeting the retinal cell layer, they were able to achieve the highest expression of the necessary gene and that the treatment was durable over several years.

Early on at REGENXBIO, we wanted to go beyond fixing single faulty or missing genes to cure diseases; we wanted to think boldly and broadly to make gene therapy widely accessible to address larger chronic diseases and public health priorities. We decided to take advantage of an existing standard of care for a range of eye diseases, and use our AAV8 vector to deliver the nucleotide sequence encoding for ranibizumab, a well-known anti-VEGF monoclonal antibody fragment, directly into cells where it could potentially be produced and secreted into the retinal tissue. This became REGENXBIO’s lead gene therapy candidate, RGX-314, which is being developed as a novel, one-time treatment for wet age-related macular degeneration (wAMD) and diabetic retinopathy (DR), diseases affecting millions of patients.

Prior to the advent of ranibizumab, millions of patients with wAMD had deteriorating visual outcomes and became legally blind within few years of diagnosis. The approval of ranibizumab has been sight-saving around the world. However, despite the fact that ranibizumab provides powerful efficacy and long-term safety — supported by extensive clinical trial evidence — real-world evidence suggests that patient compliance is a significant concern, and patients often experience vision loss with reduced frequency of treatment with ranibizumab and other approved anti-VEGF treatments. The promise of AAV-mediated antibody gene transfer is that it can potentially offer a one-time treatment in place of ongoing and often lifelong recurring anti-VEGF treatments.

At the most recent AAO conference in San Francisco, we presented the interim data from our phase 1/2a dose-escalation study of RGX-314 delivered subretinally for the treatment of wAMD. Based on these data, we are preparing to initiate additional clinical trials of RGX-314 delivered subretinally in patients with wAMD and DR. We are also exploring the use of Clearside Biomedical’s SCS Microinjector to deliver the gene therapy to the suprachoroidal space with an innovative in-office procedure, which may allow for the treatment of an expanded population of patients with wAMD and DR. If successful, our work has the potential to generate a one-time therapy that transforms the lives of millions of patients.

These results provide evidence of the powerful potential of gene therapy. While the biotechnology industry must continue to pursue gene therapy for rare monogenic diseases, it should concurrently tackle common and pervasive diseases by leveraging the potential of AAV-mediated antibody therapy. Our company is proud to be a leader in the gene therapy field, with a robust pipeline in both rare and broad-impact chronic diseases. The time has come for other pioneers in our industry to adopt a broader and bolder purview. Millions of patients are counting on us. RP

Editor’s note: This article is part of a special edition of Retinal Physician that was supported by REGENXBIO.