Pharmacokinetics of anti-VEGF drugs suggest reinjection between 4 weeks and 8 weeks

VIENNA — Calculation of the half-life of anti-VEGF drugs supports reinjection intervals between 4 weeks and 8 weeks, according to studies presented by one speaker.

“We developed an enzyme ELISA test to determine the concentration of unbound bevacizumab and ranibizumab in the anterior chamber at different time points after injection and used it in a series of prospective trials,” Carsten H. Meyer, MD, said at the Advanced Retinal Therapy meeting.

In the first trial, intravitreal injection of 1.5 mg Avastin (bevacizumab, Roche/Genentech) was performed in 30 patients with severe cataract, diabetic macular edema, age-related macular degeneration, branch retinal vein occlusion or central retinal vein occlusion. Patients were tested at 1 days to 53 days after injection. Anterior chamber tap was performed during cataract surgery. Highest values were found of on day 1, with a concentration of 33.3 µg/mL. Minimal concentration for biological activity was reached at day 29, with 5 µg/mL. Half-life was 9.82 days on average, with minor variations according to eye conditions.

“It seems reasonable, according to these findings, to perform monthly intravitreal injection of bevacizumab,” Meyer said. “In a second trial, we doubled the doses but had no significant impact.”

Lucentis (ranibizumab, Novartis/Genentech) was tested in the same way, and the highest values were found again at day 1, with 56.1 µg/mL. Minimal concentration was at day 25, and average half-life was 7.19 days.
“A little shorter than bevacizumab, although the binding affinity is higher. In this respect, our findings were in line with the CATT trial,” Meyer said.

“We are currently investigating aflibercept (Eylea, Regeneron/Bayer HealthCare). Our first results from 36 samples suggest intraocular VEGF suppression for more than 60 days, but the upper limit is still unknown,” he said.

Disclosure: Meyer has no relevant financial disclosures.