New anti-VEGF effective for AMD
New VEGF-inhibitor shows long duration efficacy with fewer injections
The new vascular endothelial growth factor (VEGF) inhibitor abicipar (Allergan plc, /Molecular AG) appears to be as effective when administered on a quarterly basis as ranibizumab is when administered on a monthly basis in eyes with neovascular age-related macular degeneration (AMD), according the pooled results of CEDAR and SEQUOIA randomised, double-masked, active-controlled, phase III clinical trials recently published in the journal Ophthalmology.
The two multi-centre studies had identical protocols and involved a total of 1,888 patients with treatment-naïve active choroidal neovascularisation secondary to AMD. They were randomised on a 1:1:1 basis to receive treatment with three different anti-VEGF regimens: abicipar 2.0mg every eight weeks after three initial doses at baseline and weeks four and eight (Q8); abicipar 2.0mg every 12 weeks after three initial doses at baseline and weeks four and 12; or ranibizumab 0.5mg every four weeks.
Overall, 1,620 (85.8%) patients completed the first 52 weeks of the study. The mean best-corrected visual acuity (BCVA) improved in all treatment groups, with the improvement after the initial doses maintained through week 52. At week 52, there was a mean gain in BCVA from baseline of 7.5 letters in patients receiving abicipar every eight weeks, 6.4 letters in those receiving it once every 12 weeks and 8.4 letters in the ranibizumab group.
In addition, the mean central retinal thickness deceased by 144µm and 145µm in the eight- and 12-week abicipar groups, respectively, and by 144µm in the ranibizumab group. Optical coherence tomography showed that abicipar-treated eyes had a more rapid and more complete resolution of intraretinal and subretinal fluid than ranibizumab during the initial dose phase of the study.
However, the incidence of inflammatory intraocular adverse events was 15.4% and 15.3%, among patients receiving abicipar once every eight weeks and once every 12 weeks, respectively, compared to only 0.3% of patients receiving ranibizumab. Most inflammatory intraocular adverse events were mild or moderate in severity and responded to topical corticosteroids, but 32% of patients with the complication required oral and/or injectable corticosteroids.
The study’s authors note that inflammation in the abicipar group may have been the result of impurities remaining from the bio-engineered E. coli cells used to generate the abicipar molecules. Molecular Partners AG has since adopted additional purification measures which may eliminate the problem.
Abicipar pegol is the first designed ankyrin repeat protein (DARPin) to enter therapeutic use. It is genetically engineered antibody-mimetic protein that binds all isoforms of VEGF-A with high affinity and specificity.