OCT 12, 2019

Gene Therapy for Wet AMD?

Could a one-time gene therapy replace monthly anti-VEGF injections? If phase 1/2a findings hold true, RGX-314 carries the potential to alleviate—or even eliminate—injection burden for patients with wet AMD, according to Jeffrey S. Heier, MD, who presented data at the Late Breaking Developments session during Friday’s Retina Subspecialty Day.

A novel AAV8 vector. Developed by Regenxbio, RGX-314 is an experimental subretinal gene therapy designed to deliver high and long-lasting gene expression with a low immune response. The proprietary NAV AAV8 platform carries a gene encoding for an anti-VEGF monoclonal antibody fragment, driving sustained protein production by the retinal cells.

Fully enrolled trial. The study tested five different doses of RGX-312 in 42 patients who were responsive to and dependent on anti-VEGF treatment. Each received subretinal delivery of the experimental drug and were monitored monthly for safety and need for additional anti-VEGF therapy.

Safety first. Overall, RGX-314 was well tolerated by all 42 patients, Dr. Heier noted. There were no drug-related serious adverse events, immune responses, ocular inflammation, or postoperative inflammation beyond those typically seen after vitrectomy. Most adverse events related to RGX-314 were deemed mild.

Visual gains hint at efficacy. Investigators observed a dose-dependent increase in RGX-314 protein in aqueous samples across the five arms. The latest data—which includes six patients with 1.5 years of follow-up—reveals promising long-term results, including a 9-letter gain in visual acuity along with stable anatomic outcomes. “Three of the six patients were injection free at 18 months,” Dr. Heier said, adding that these patients demonstrated stable protein production over one year and gained 11 letters in the process.

So, what does the future hold? Dr. Heier explained that RGX-314 will move on to phase 2 trials by the end of 2019, and the therapy will also be tested in patients with diabetic retinopathy. In addition, investigators will study the feasibility of in-office suprachoroidal delivery of RGX-314 using Clearside’s proprietary microinjector.—Keng Jin Lee, PhD

Financial disclosures: Dr. Heier: 4DMT: C; Adverum: C,O; Aerie Pharmaceuticals: C,S; Aerpio: C,S; Aldeyra: C,O; Alkahest: C; Allegro: C,O; Allergan, Inc.: C; Annexon: C; Apellis: C,S; Array Biopharma: C; Asclepix: C; Chengdu Kanghong Biotech: C,S; Clearside: S; Daiichi: S; Digital Surgery Systems: O; Eloxx: C; Galimedix: C; Genentech: C,S; Generation Bio: C; Graybug: S; Gyroscope: S; Hemera: S; Interface: C; irenix: C; Janssen R&D: C,S; jCyte: C,O; Kala: C; Kalvista: S; Kodiak: C; NGM Biopharmaceuticals: C; Notal Vision: C,S; Novartis Pharma: C,S; Ocugenix: C; Ocular Therapeutix: C,O; Omeicos: C; Ophthotech: S; Optos: S; Optovue: S; Orbit Biomedical: C; Regeneron Pharmaceuticals: C,S; Regenxbio: C,S; Retrotope: C; Santen: C; Scifluor: C; Shire: C; Stealth Biotherapeutix: C,S; Takeda: C; ThromboGenics: S; Voyant: C.

Disclosure key. C = Consultant/Advisor; E = Employee; L = Speakers bureau; O = Equity owner; P = Patents/Royalty; S = Grant support.