FDA Approves Aflibercept for Diabetic Retinopathy

The US Food and Drug Administration (FDA) has approved aflibercept (Eylea) for the treatment of all stages of diabetic retinopathy.

The anti-VEGF treatment is administered as an intravitreal injection. For diabetic retinopathy treatment, aflibercept may be dosed every 8 weeks after 5 initial monthly injections, or every 4 weeks.

"Millions of people have been robbed of their vision due to the progression of diabetic retinopathy," said David Brown, MD, FACS, an investigator for the PANORAMA trial and Director of Research at Retina Consultants of Houston. "The prevention of worsening diabetic retinopathy with Eylea provides a compelling rationale for early treatment of patients with this disease, particularly since eyes dosed with Eylea as infrequently as every 16 weeks showed significant improvements in the pivotal PANORAMA trial."

The FDA’s decision to approve was supported by results of the PANORAMA trial, a phase 3, randomized, controlled trial with 402 patients with moderately severe to severe non-proliferative diabetic retinopathy (NPDR) without diabetic macular edema (DMA). The prospective trial compared aflibercept to sham injections. Patients were randomized to aflibercept every 8 weeks after 5 initial monthly doses (n = 134), aflibercept every 16 weeks after 3 initial monthly doses and an 8-week interval (n = 135), or sham (n = 133).

Meeting the primary endpoint, 65% of patients in the 16-week group and 80% of patients in the 8-week group achieved a ≥2 step improvement in the diabetic retinopathy severity scale (DRSS) from baseline at week 52, compared to 15% in the sham group.

Secondary endpoints included patient progression to proliferative diabetic retinopathy (PDR), which occurred in 2% of the 16-week group (Hazard Ratio [HR] 0.11) and 0% in the 8-week group (HR 0.00), compared to 12% in the sham group (P <.01 for both comparisons to sham). Another secondary endpoint was the composite of developing PDR or anterior segment neovascularization (ASNV), which occurred in 4% of the 16-week group (HR 0.15) and 2% in the 8-week group (HR 0.12), compared to 20% in the sham group (P <.01 for both comparisons to sham).

Charles Wykoff, MD, PhD, Retina Consultants of Houston, and Deputy Chair of Ophthalmology at Blanton Eye Institute, Houston Methodist Hospital spoke with MD Magazine® about the study’s 52-week primary endpoints at the 2019 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) in Vancouver, BC.

Wykoff highlighted the secondary endpoints in the PANORAMA study as the markers of what providers and patients care about most—vision-threatening complications such as proliferative diabetic retinopathy and DME.

“At some level does it really matter what the color fundus photograph looks like? Does it really matter how many hemorrhages a patient has?” asked Wykoff. “It's really a debatable question, but certainly I think what we all care about are the vision-threatening complications: proliferative disease and DME and there was a highly significant difference between the arms.”

The PANORAMA trial is a 2-year program, so further long-term outcome data are expected to be announced in the coming year.