Real ROP Progress

What does EYLEA mean for the future of ROP treatment?
 

ROP is a leading cause of childhood blindness worldwide. Until the approval of EYLEA for the treatment of ROP, the only FDA-approved treatment in common use was laser photocoagulation – a complex and lengthy procedure that permanently ablates retina tissue and is stressful not only for infant patients but also the family navigating a delicate time after a preterm birth. Now, physicians will have an FDA approved pharmacological medication that will help treat this challenging disease and potentially help preterm infants preserve their vision.

How did the approval of EYLEA for ROP come about?
 

As you may know, EYLEA (aflibercept) injection was first approved in 2011 for the treatment of adult patients with wet age related macular degeneration (wet AMD). Over the years, EYLEA was approved to treat other diseases of ocular angiogenesis, including diabetic macular edema, diabetic retinopathy, and retinal vein occlusion.

In 2019, the FDA issued a pediatric written request to study EYLEA in the treatment of preterm infants with ROP. Vascularization of the retina occurs late in gestation and preterm birth interrupts normal retinal development, which sometimes leads to an overexpression of VEGF and pathologic neovascularization. EYLEA binds to VEGF preventing the activation of VEGF receptors and halting the formation of abnormal blood vessels seen in patients with ROP.

In short, Regeneron conducted two phase III studies – FIREFLEYE and BUTTERFLEYE – which investigated EYLEA 0.4 mg versus laser photocoagulation in infants with ROP. In both trials, approximately 80 percent of EYLEA-treated infants achieved an absence of both active ROP and unfavorable structural outcomes at 52 weeks of age. Though numerically similar to laser photocoagulation, the primary endpoint of non-inferiority was not met because of higher than expected levels of efficacy with the laser (based on previous ROP trials). Notably, per an exploratory analysis, the time required to complete treatment administration per patient was considerably less for EYLEA than for laser (FIREFLEYE: 4 minutes versus 122 minutes; BUTTERFLEYE: 11 minutes versus 129 minutes). No new safety signals were observed in either trial.

This data supported our supplemental application to the FDA and we received approval on February 8, 2023.

With five indications to EYLEA’s name, what comes next?
 

Also in February 2023, we announced the FDA acceptance of our Biologic License Application for aflibercept 8 mg for the treatment of wet AMD and DME. The application was supported by data from two Phase III clinical trials – PHOTON and PULSAR – wherein aflibercept 8 mg demonstrated non-inferiority in vision gains in both 12 and 16-week dosing regimens compared to an EYLEA 8-week dosing regimen in patients with wet AMD and DME.

Furthermore, 91 percent and 89 percent of DME patients and 79 percent and 77 percent of wet AMD patients respectively randomized to 12 and 16-week dosing maintained those intervals through 48 weeks. The safety of aflibercept 8 mg was similar to EYLEA in both trials, and consistent with the known safety profile of EYLEA from previous clinical trials.

These outcomes have demonstrated that aflibercept 8 mg can potentially lead to significant and clinically meaningful outcomes with a reduced treatment burden for patients. If approved, aflibercept 8mg could become the next standard of care for these serious retinal conditions.