I am always fascinated by how much the field of pediatric retina advances between our annual issues. This year was especially exciting as we saw the approval of 0.4 mg aflibercept (Eylea; Regeneron) for the treatment of retinopathy of prematurity (ROP) by the US Food and Drug Administration (FDA). Having another drug approved for the treatment of ROP, in addition to 0.2 mg ranibizumab (Lucentis; Genentech), is a milestone in many ways, but it is particularly important that another pharmaceutical company would perform clinical trials in premature infants. This type of trial has been a lightning rod that companies have been unwilling to touch.

The FDA approval was interesting in that the FIREFLEYE and BUTTERFLEYE phase 3 studies did not meet their noninferiority primary outcome, which was the proportion of aflibercept-treated infants without active ROP and unfavorable structural outcomes compared to laser-treated infants 24 weeks after starting treatment. The main reason for this outcome was that the laser-treated babies did better than in previous ROP studies. The approval stemmed from the fact that 80% of babies did achieve absence of ROP and unfavorable structural outcomes in this orphan indication, which is better than no treatment, and the safety was similar to laser.

This outcome is similar to that of the RAINBOW phase 3 study in which 80% of babies treated with ranibizumab reached treatment success compared to 66% of laser treated infants at 24 weeks. Moreover, there was excellent long-term safety in the 2-year RAINBOW extension study, with a reduction in high myopia and quality-of-life measures.

Hopefully, these approvals will end the pharmaceutical companies’ reluctance to enter this space. In the case of Regeneron, the approval extends the patent expiration date of Eylea by 6 months due to the pediatric exclusivity extension. Over that time, Regeneron makes roughly $3 billion in sales of Eylea.¹ Companies developing aflibercept biosimilars will have to wait those additional 6 months before they can begin sales — from a business standpoint for Regeneron, this is well worth the development costs and risk of getting an ROP indication for Eylea.

In this issue, we look at the new classification scheme for ROP and tips and tricks for pediatric retinal detachments and how to diagnose and manage Coats disease. We hope you enjoy our pediatric retina issue and hope researchers will continue to push forward in this field to bring additional therapies to these infants. RP

REFERENCES

1. Regeneron. Regeneron reports fourth quarter and full year 2022 financial and operating results. News release. February 3, 2023. https://investor.regeneron.com/news-releases/news-release-details/regeneron-reports-fourth-quarter-and-full-year-2022-financial/