Regenxbio-AbbVie in-office eye disease gene therapy clears interim phase 2 test

Regenxbio and AbbVie have taken a small step toward in-office administration of their eye disease gene therapy candidate. Interim phase 2 data suggest the prospect can be given safely at the doctor’s office, opening up a convenient delivery option for the wet age-related macular degeneration (AMD) treatment.

AbbVie paid $370 million for rights to the candidate, ABBV-RGX-314, in 2021. By then, Regenxbio was testing subretinal administration of the gene therapy in pivotal trials while running phase 2 studies of an alternative, suprachoroidal delivery route. Suprachoroidal administration could enable physicians to give the gene therapy in their offices, rather than requiring patients to go to operating rooms.

The interim phase 2 results show suprachoroidal delivery, which is enabled by Clearside Biomedical tech, may be a viable alternative. None of the 106 patients, across three dose levels, suffered drug-related or ocular serious adverse events. Regenxbio reported two cases of intraocular inflammation but they were mild and resolved by the next visit. No patients who received a short course of prophylactic steroid eye drops had intraocular inflammation.

Talking on a Regenxbio conference call to discuss the data, Eye Associates of New Mexico’s John Pitcher, M.D., and Wills Eye Hospital’s Allen Ho, M.D., respectively said the use of eye drops is “very palatable to patients and retina specialists” and “a completely acceptable way to control” the inflammation risk.

On the efficacy front, BCVA, a vision test, and central retinal thickness were stable six months after the administration of the one-time gene therapy. Patients received fewer anti-VEGF injections, the current standard of care for wet AMD, too. At the third dose level, Regenxbio tracked an 80% drop in injection burden. Half of the patients in that cohort needed no eye injections.

The potential for ABBV-RGX-314 to keep vision stable without frequent injections is key to Regenxbio’s pitch for the gene therapy. On the conference call, Regenxbio presented data showing that vision gains in recipients of the VEGF drug Lucentis fade between the second and fifth years of treatment, potentially because of noncompliance with the burdensome series of injections.

“I frequently see patients experience setbacks or vision loss due to inadequate treatment with the current standard of care. It's not always easy to avoid. Patients may travel from far distances to receive injections ... so they may become sick or have unreliable transportation options,” Pitcher said. “A one-time, in-office gene therapy option could help and obviously eliminate a lot of the obstacles.”

ABBV-RGX-314 is designed to reduce the need for injections by using a vector encoding for an anti-VEGF antibody fragment to cause sustained protein production by the patient's retinal cells. Regenxbio thinks the candidate has multi-billion-dollar sales potential. Phase 3 trials of the subretinal candidate are due to wrap up in 2025. The next steps for the suprachoroidal program will depend on discussions with AbbVie.