ROP is a leading cause of childhood blindness worldwide
TARRYTOWN, N.Y., Oct. 12, 2022 /PRNewswire/ -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced the U.S. Food and Drug Administration (FDA) has accepted for Priority Review the supplemental Biologics License Application (sBLA) for EYLEA® (aflibercept) Injection to treat Retinopathy of Prematurity (ROP) in preterm infants. The target action date for the FDA decision is February 11, 2023.
ROP is a leading cause of childhood blindness worldwide. Each year in the U.S., between 1,100 to 1,500 infants develop disease severe enough to require medical treatment. The rare eye disease often impacts infants who are born before 31 weeks of pregnancy have been completed or who weigh less than 1,500 grams (3.3 lbs) pounds at birth. As retinal blood vessels are often only fully developed when an infant is full-term (~9 months of pregnancy), these infants are at risk of developing retinal blood vessels that are abnormal (retinal neovascularization) potentially leading to retinal detachment and irreversible vision loss. Mild cases of ROP may get better without treatment, but some cases require treatment (for which the current standard of care is laser photocoagulation) to keep ROP from causing significant visual impairment and even blindness.
The sBLA is supported by data from two randomized global Phase 3 trials – FIREFLEYE (N=113) and BUTTERFLEYE (N=120) – investigating EYLEA 0.4 mg versus laser photocoagulation (laser) in infants with ROP. In both trials, approximately 80% of EYLEA-treated infants achieved an absence of both active ROP and unfavorable structural outcomes at 52 weeks of age, although their primary endpoint of non-inferiority was not met due to laser demonstrating comparable levels of efficacy that were higher than what have been historically observed in similar 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 EYLEA safety signals were observed in either trial. Comparing EYLEA to laser, ocular adverse events (AEs) among patients occurred in 39% versus 37% in FIREFLEYE and 18% versus 26% in BUTTERFLEYE, with serious ocular AEs occurring in 8% for both groups in FIREFLEYE and 6.5% versus 11% in BUTTERFLEYE. AEs in both trials were consistent with infant prematurity or to the injection procedure, and with the AEs in similar ROP trials.
The results of FIREFLEYE were published in Journal of the American Medical Association, and data from BUTTERFLEYE were recently presented at ROP Update 2022 meeting in the U.S. Both trials were conducted pursuant to FDA Pediatric Written Request, and a Pediatric Exclusivity Determination is under review by FDA with a response expected by early 2023. A Pediatric Exclusivity Determination is granted if the specifications of the Pediatric Written Request are met, regardless of whether a pediatric indication is approved.
EYLEA was granted orphan drug designation by the FDA for the treatment of ROP in July 2019. The safety and efficacy of EYLEA for the treatment of ROP have not been fully evaluated by the FDA and other regulatory authorities.
The lead sponsors of the trials were Regeneron for BUTTERFLEYE and Bayer for FIREFLEYE. Bayer and Regeneron are collaborating on the global development of EYLEA. Regeneron maintains exclusive rights of EYLEA in the United States. Bayer has licensed the exclusive marketing rights outside the United States, where the companies share equally the profits from sales of EYLEA.
About EYLEAEYLEA is a VEGF inhibitor formulated as an injection for the eye. It is designed to block the growth of new blood vessels and decrease the ability of fluid to pass through blood vessels (vascular permeability) in the eye by blocking VEGF-A and placental growth factor (PLGF), two growth factors involved in angiogenesis. The EYLEA safety and efficacy profile is supported by a robust body of research that includes eight pivotal Phase 3 trials, 10 years of real-world experience and more than 50 million EYLEA injections globally.
IMPORTANT EYLEA SAFETY INFORMATION AND INDICATIONS
INDICATIONSEYLEAâ (aflibercept) Injection 2 mg (0.05 mL) is indicated for the treatment of patients with Neovascular (Wet) Age-related Macular Degeneration (AMD), Macular Edema following Retinal Vein Occlusion (RVO), Diabetic Macular Edema (DME), and Diabetic Retinopathy (DR).
CONTRAINDICATIONS
- EYLEA is contraindicated in patients with ocular or periocular infections, active intraocular inflammation, or known hypersensitivity to aflibercept or to any of the excipients in EYLEA.
WARNINGS AND PRECAUTIONS
- Intravitreal injections, including those with EYLEA, have been associated with endophthalmitis and retinal detachments. Proper aseptic injection technique must always be used when administering EYLEA. Patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay and should be managed appropriately. Intraocular inflammation has been reported with the use of EYLEA.
- Acute increases in intraocular pressure have been seen within 60 minutes of intravitreal injection, including with EYLEA. Sustained increases in intraocular pressure have also been reported after repeated intravitreal dosing with VEGF inhibitors. Intraocular pressure and the perfusion of the optic nerve head should be monitored and managed appropriately.
- There is a potential risk of arterial thromboembolic events (ATEs) following intravitreal use of VEGF inhibitors, including EYLEA. ATEs are defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause). The incidence of reported thromboembolic events in wet AMD studies during the first year was 1.8% (32 out of 1824) in the combined group of patients treated with EYLEA compared with 1.5% (9 out of 595) in patients treated with ranibizumab; through 96 weeks, the incidence was 3.3% (60 out of 1824) in the EYLEA group compared with 3.2% (19 out of 595) in the ranibizumab group. The incidence in the DME studies from baseline to week 52 was 3.3% (19 out of 578) in the combined group of patients treated with EYLEA compared with 2.8% (8 out of 287) in the control group; from baseline to week 100, the incidence was 6.4% (37 out of 578) in the combined group of patients treated with EYLEA compared with 4.2% (12 out of 287) in the control group. There were no reported thromboembolic events in the patients treated with EYLEA in the first six months of the RVO studies.
ADVERSE REACTIONS
- Serious adverse reactions related to the injection procedure have occurred in