REGENXBIO Eyes Q4 Pivotal Readout for One-Time Wet AMD Gene Therapy

Key Points

• REGENXBIO expects top-line results in Q4 from the pivotal ATMOSPHERE and ASCENT trials of one-time wet AMD gene therapy sura-vec. Positive data could support a regulatory submission in 2027, with AbbVie leading the application process.
• Sura-vec is designed to produce anti-VEGF protein in the eye after a subretinal procedure, potentially reducing repeated injections. Earlier-stage studies showed substantial declines in injection requirements, but those results do not establish pivotal efficacy or approval.
• The company reported no drug-related serious adverse events at pivotal doses and said its Rockville facility could produce nearly 350,000 doses annually. Commercial uptake will depend on pivotal safety and efficacy, reimbursement, physician experience and initial use among patients with the highest injection burden.

REGENXBIO NASDAQ: RGNX outlined its clinical, manufacturing and commercialization plans for sura-vec, an investigational one-time subretinal gene therapy for wet age-related macular degeneration, or wet AMD, during a company event featuring retina specialists and executives.

The company said it expects to report top-line results later in the fourth quarter from its two pivotal wet AMD studies, ATMOSPHERE and ASCENT, in a planned joint release with partner AbbVie. REGENXBIO said the data could support a regulatory submission in 2027, with AbbVie, which owns the investigational new drug application, expected to lead the biologics license application process.

Program Designed for Broad Wet AMD Population

Chief Medical Officer Steve Pakola said the company designed the sura-vec program to address treatment burden associated with repeated anti-VEGF injections. Wet AMD patients commonly require recurring injections to control disease activity, but panelists said real-world adherence declines over time.

Lejla Vajzovic, a retina specialist at Duke University, said approximately 200 million people worldwide have AMD and projected growth could bring that total to 288 million by 2040. She said wet AMD contributes disproportionately to severe vision loss and that patients face varying levels of disease activity, including a substantial group requiring injections more often than every eight weeks.

Vajzovic also noted that roughly half of wet AMD patients have disease in both eyes. She said treatment adherence is a key challenge, citing figures presented during the event showing that 30% of patients are lost to follow-up in the first year and about half by year three.

Sura-vec uses an adeno-associated virus vector to deliver an anti-VEGF protein-producing gene through a subretinal surgical procedure. REGENXBIO and the physicians emphasized that the approach is intended to provide sustained protein expression in the eye, potentially reducing the frequency of supplemental injections.

Pakola said the program includes more than 1,400 enrolled participants across trials, with more than 100 patients dosed. The company characterized it as the largest and most comprehensive gene therapy development program conducted to date. More than 500 specialists have been trained to administer sura-vec, including more than 300 in the U.S., according to the company.

Pivotal Studies and Earlier Data

The ATMOSPHERE study compares low- and high-dose sura-vec with monthly ranibizumab in the U.S. The global ASCENT study compares the two sura-vec doses with every-eight-week aflibercept. Both studies use change in best-corrected visual acuity at 54 weeks as the primary endpoint and are designed to evaluate non-inferiority against their respective active controls.

Pakola said patients in the trials were treatment experienced and could have received up to four years of prior treatment. Patients underwent a ranibizumab screening injection and were assessed for an anatomical response one week later before enrollment, a design the speakers said enabled inclusion of both lower- and higher-disease-activity patients.

Rahul Khurana, a retina specialist with Northern California Retina Vitreous Associates, reviewed earlier-stage results that he said showed maintained vision, stable retinal anatomy and reduced treatment burden. In a Phase II pharmacodynamic study, he said injection needs declined by more than 75% from pre-treatment levels, while 53% to 60% of patients in the dose groups were injection-free during the reported period.

Khurana also discussed five-year Phase I findings in high-treatment-burden patients. He said annual injection rates declined by about 64% to 65% in two cohorts, while visual acuity was maintained or improved. These earlier results are not the pivotal readout and do not establish efficacy for approval.

Safety and Surgical Delivery

Arshad Khanani, managing partner and director of clinical research at Sierra Eye Associates, said no drug-related serious adverse events had been seen at pivotal doses across the studies discussed at the event. He said observed effects included routine post-procedure inflammation and conjunctival hemorrhage associated with surgery.

Khanani said the development program refined the placement of subretinal injection blebs after earlier experience with peripheral retinal pigmentary changes. According to his presentation, the optimized procedure used in the pivotal studies has not produced central macular pigmentary changes in the Phase II cohort, and peripheral changes were reported to stabilize without affecting best-corrected visual acuity.

Gaurav Shah, chair of ophthalmology at Sutter Health, said subretinal treatment is delivered using familiar vitrectomy procedures and existing outpatient surgical infrastructure. He said retina specialists already perform such procedures in ambulatory surgery centers and hospitals, and he cited established billing codes for vitrectomy and subretinal administration.

Speakers noted that post-surgical steroids would still be used for a limited period following vitrectomy, but said sura-vec does not require the extended prophylactic steroid regimens associated with certain intravitreal gene therapy approaches.

Manufacturing and Commercial Considerations

REGENXBIO said its Rockville manufacturing facility could produce nearly 350,000 annual sura-vec doses and up to 2,500 doses annually for its Duchenne muscular dystrophy program. The company said the facility was inspected in connection with RGX-121 and received no observations.

Chief Commercial Officer Ram Palanki argued that adoption could be supported by the concentration of wet AMD patients, retina specialists and surgical capacity at a relatively limited number of treatment sites. He said the company’s pivotal footprint overlaps substantially with those locations and that existing reimbursement precedents for retinal gene and cell therapies could support access if sura-vec is approved.

Panelists said uptake would ultimately depend on pivotal efficacy and safety data, patient selection, payer coverage and physician experience. Several physicians said they would likely first consider gene therapy for patients with the greatest injection burden, while broader use could follow if clinical outcomes and safety support it.

About REGENXBIO (NASDAQ:RGNX)

REGENXBIO Inc is a biotechnology company focused on developing and commercializing gene therapies for serious diseases. The company's programs are based primarily on its proprietary NAV AAV Technology Platform, which uses adeno-associated virus (AAV) vectors to deliver genetic material to targeted cells. Its research has emphasized conditions affecting the central nervous system, muscles and other tissues.

REGENXBIO's pipeline has included investigational therapies such as RGX-121 for mucopolysaccharidosis type II, RGX-111 for mucopolysaccharidosis type I and RGX-202 for Duchenne muscular dystrophy.

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