A new study published in The Lancet has unveiled promising results for RGX-314, a novel gene therapy aimed at treating wet macular degeneration, one of the leading causes of irreversible vision loss.

The study, co-authored by Houston Methodist Hospital Ophthalmologist Dr. Charles Wykoff, offers hope for a potential long-term solution to a debilitating condition that primarily affects the elderly.

"This gene therapy offers a potential one-and-done treatment for wet age-related macular degeneration, which would be a tremendous advantage for many patients who currently need to receive frequent injections into their eye to maintain as much vision as possible, often indefinitely," said Dr. Wykoff, a vitreoretinal surgeon and retinal disease expert.

The data recently published in The Lancet represents the complete results from the Phase 1/2a trial of 42 patients treated and followed for at least two years. The therapy is currently under investigation in ongoing, global Phase 3 clinical trials.

The Lancet study showed a dose-response and sustained disease control in patients who received higher doses of the therapy.

Delivery of RGX-314 involves injecting a virus into a bleb (bubble) under the retina during a vitrectomy surgery in order to convert the eye into an "intraocular bio-factory." The method aims to replace the current treatment of frequent eye injections with a single procedure that enables the eye to produce the necessary medication internally.

"Instead of injecting medicine into the eye, we are utilizing the native cellular machinery present inside of the eye to create a factory that produces ranibizumab, the same anti-VEGF agent that we have been injecting into eyes for about 20 years," Dr. Wykoff said.

The trial consisted of 42 intensively pretreated patients randomly assigned to one of five cohorts with escalating dose size. The lower doses given in cohorts one and two were deemed subtherapeutic but the doses in cohorts three, four and five showed significant efficacy at reducing the need for ongoing injections.

"A good reflection of efficacy in this patient population is the need for ongoing retreatments, which was meaningfully reduced in cohorts three, four and five after treatment," Dr. Wykoff explained. "In these groups, we observed a 60%-80% reduction in the number of injections they received, which is clinically meaningful. After the gene therapy, on average, patients received one to four injections a year, compared to about ten injections per year before surgery."

Additionally, visual acuity increased in groups three, four and five, particularly among cohorts three and four.

Despite the small sample size, the results were compelling, said Dr. Wykoff: "Each of these cohorts had less than 10 patients, but our findings show that the drug clearly works in cohorts three, four and five."

While the therapy shows significant promise, safety remains a priority.

"There's been no clinical evidence of intraocular inflammation, which is reassuring and distinct from some other forms of ocular gene therapy," Wykoff stated.

However, pigmentary changes were observed in the area of the bleb, leading to recommendations that providers direct the gene therapy to the inferior peripheral retina in order to avoid damaging important visual structures such as the macula.

The ongoing Phase 3 clinical trials, ASCENT and ATMOSPHERE, are critical for the potential FDA approval of RGX-314.

"This has the possibility of becoming the first FDA-approved gene therapy for wet AMD," Dr. Wykoff said. "Our hope is that it will be a long-term therapy that extends well beyond two years."