FDA approval of visual gains and safety of aflibercept (8mg) were announced on August 18th, indicated for the treatment of patients with wet age-related macular degeneration (wAMD), diabetic macular edema (DME) and diabetic retinopathy (DR). According to the clinical sponsor (Regeneron), the recommended dose for aflibercept is 8mg every 4 weeks (monthly) for the first 3 months across all indications, followed by 8mg every 8 to 16 weeks (2 to 4 months) in wet AMD and DME and every 8 to 12 weeks (2 to 3 months) for DR. The sponsor’s summary of the results were built upon the 48-week results of PULSAR and PHOTON – two double-masked, active-controlled pivotal trials evaluating the 8mg dose compared to 2mg. Both the PULSAR trial in wet AMD (N=1,009) and PHOTON trial in DME (N=658) met their primary endpoint, demonstrating non-inferior and clinically equivalent vision gains at 48 weeks with both 12- and 16-week dosing regimens after only 3 initial monthly doses, compared to an aflibercept 8-week dosing regimen after initial monthly doses (3 in PULSAR and 5 in PHOTON). According to the sponsor, the vast majority of patients randomized at baseline to the 8mg dose 12- or 16-week dosing regimens (following 3 initial monthly doses) were able to maintain these dosing intervals through 48 weeks. In addition, the most common adverse reactions (≥3%) reported were cataract, conjunctival haemorrhage, intraocular pressure increased, ocular discomfort/eye pain/eye irritation, vision blurred, vitreous floaters, vitreous detachment, corneal epithelium defect and retinal haemorrhage.
Aflibercept, formerly VEGF Trap Eye, is a recombinant fusion protein consisting of portions of human VEGF (Vascular Endothelial Growth Factor) receptors 1 and 2 extracellular domains fused to the Fc portion of human IgG1, specifically purified and formulated for injection into the eye and capable of binding all forms of (VEGF-A) and Placental Growth Factor (PlGF). The drug acts as a soluble decoy receptor binding VEGF-A and PIGF thereby inhibiting the binding and activation of the cognate VEGF receptors. The earlier clinical trials, involving 2,412 patients, was approval under priority review based on the VIEW 1 and VIEW 2 multicentre, phase 3 trial data. the release of 96-week data from the VIEW 1 and VIEW 2 studies. According to the original results, the visual acuity (VA) gain from baseline in the aflibercept every 8 weeks group was 7.6 letters at week 96 compared to 8.4 letters at week 52, averaging 11.2 injections over the two years and 4.2 injections during the second year.
Following the announcement on the approval of the 8mg dose, Peter Kaiser, M.D., at the Cole Eye Institute and Professor of Ophthalmology at Cleveland Clinic Lerner College of Medicine, stated, “the FDA approval of EYLEA HD is an important advancement in retinal care. With EYLEA HD, patients with wet age-related macular degeneration or diabetic retinal disease can now receive less frequent injections after their initial monthly doses and still experience the similar visual gains, anatomic improvements and safety profile of EYLEA.” In addition, Allen C. Ho M.D., Director of Retina Research and Co-Director of the Retina Service of Wills Eye Hospital further commented that, “I look forward to offering EYLEA HD to my patients as a new treatment option that builds off of the established efficacy and safety profile of EYLEA. In its clinical trial program, EYLEA HD demonstrated an unprecedented ability to maintain vision with extended dosing intervals, which created an exciting new advancement in the treatment of our patients with serious retinal diseases.”