A Breakthrough Year in Retina Research

What an exciting year 2019 turned out to be for the management of retinal disease. As the year draws to a close, it's an ideal time to take a look back at some of the biggest stories, including the introduction of a new US Food and Drug Administration (FDA)–approved pharmaceutical agent for neovascular age-related macular degeneration (nAMD), positive data on interventions capable of slowing geographic atrophy (GA) progression, intriguing trial results for patients at high risk for nonproliferative diabetic retinopathy (NPDR), and further exploration of the power of artificial intelligence (AI).

New Treatments for AMD

AMD remains a leading cause of blindness secondary to one of two advanced stages: nAMD and GA.^[1] This year brought clinically relevant advances on both fronts.

nAMD

Brolucizumab (Beovu) received FDA approval for the treatment of nAMD in October 2019. Brolucizumab, a humanized, monoclonal single-chain antibody fragment, inhibits vascular endothelial growth factor (VEGF) A—and at 26 kD, it is smaller than the other anti-VEGF agents. At 6 mg per dose, the molar anti-VEGF binding capacity is substantially greater as well.

The FDA's approval was based on the phase 3 HAWK and HARRIER double-masked, randomized trials, which used aflibercept (Eylea) as the comparator.^[2] During the first 4 months of the 2-year studies, the matched phase, brolucizumab was found to achieve more complete drying of the retina. At week 16, 34% vs 52% of patients had residual fluid following treatment with brolucizumab and aflibercept, respectively. Subsequently, patients receiving brolucizumab were treated every 8 or 12 weeks depending on disease activity, with 39%-45% of these patients maintained at quarterly dosing through the week 96 endpoint.

GA

Characterized by loss of choriocapillaris, retinal pigment epithelium, and photoreceptors, GA represents the single greatest unmet medical need in patients with retinal disease,^[3] with no approved therapeutic strategies to prevent onset or progression.

Strong genetic and physiologic data have implicated complement dysregulation in GA pathogenesis,^[4] although targeting complement in an attempt to slow GA enlargement has yet to yield a validated pharmaceutical therapy.^[5]

Renewed hope has been brought to the field, however, by two recent phase 2 clinical trials reporting positive data. First, prevention of complement C3 cleavage with pegcetacoplan resulted in statistically significant reductions in GA growth by 20%-29% at 1 year, which appeared to increase with longer drug exposure and be dose dependent.^[6] Second, inhibition of the downstream complement component C5 with avacincaptad pegol (Zimura) similarly resulted in statistically significant reductions in GA by about 27% at 1 year.^[7] Both of these molecules are being investigated in phase 3 trials.

Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.

Cite this: A Breakthrough Year in Retina Research - Medscape - Dec 27, 2019.

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