Employing a therapeutic approach consisting of pan-vascular endothelial growth factor (VEGF) blockers such as ranibizumab (Lucentis, Genentech) and/or bevacizumab (Avastin, Genentech) as an induction therapy, followed by a selective VEGF blocker such as pegaptanib (Macugen, OSI/Eyetech) as a maintenance therapy, appears to be effective in patients with neovascular age-related macular degeneration, according to the interim results of the LEVEL study. This approach may be preferred for many patients from the standpoint of systemic safety.
Preliminary results of the ongoing LEVEL study have shown that this induction-maintenance strategy not only is effective for patients with NV-AMD but it also is a potentially safer option than treating these patients with non-selective VEGF antagonists alone, he said.
Ongoing, phase IV study
Booster injections were allowed and given at the discretion of the investigator to any patient who experienced a worsening of symptoms, visual acuity (VA) loss, or macular thickening during the trial. Inclusion criteria included a VA of 20/20 to 20/400, any lesion subtype ≤ 12 disc areas, and an OCT center point thickness ≤ 275 μm or retinal thinning ≥ 100 μm following induction therapy.
The interim study results show that patients needed to have at least one but no more than three induction injections (2.7 average). During the induction phase, more than 88% of patients gained a VA of more than three lines, and the average VA improved from 50 Early Treatment Diabetic Retinopathy Study (or ETDRS) letters prior to induction to 65.5 letters at the beginning of the maintenance phase. During maintenance using pegaptanib given every 6 weeks, Dr. Friberg said that the mean VA generally was stable. At the end of the 54 weeks, VA averaged 60 letters, a more than two-line gain compared with pre-induction levels.
About a third of the patients received bevacizumab, a third ranibizumab, and the other third used a combination of those drugs and sometimes with photodynamic therapy.
Data also showed that during the 54 weeks, 46% of patients did not require booster treatment. Of the patients who required booster treatment, 50% required only one booster injection. Booster injections could be given if the patient lost two lines of vision or if the optical coherence tomography (OCT) thickness was more than 300 μm. This strategy served as a fall-back treatment during the trial, but fortunately was largely unnecessary, Dr. Friberg said, adding that the adverse events reported were consistent with VISION trial results, with no evidence of increased risk of systemic or ocular events.
Anti-VEGF therapies have become the cornerstone for the treatment of patients with NV-AMD, he said. Two commonly used therapies are ranibizumab and bevacizumab, and both drugs are pan-VEGF blockers, meaning that they block all the isoforms of VEGF. Alternatively, pegaptanib is a selective blocker of VEGF 165 only. According to Dr. Friberg, employing a selective blocker for maintenance therapy can be very advantageous to the patient, because it may be less than optimal to block all VEGF proteins in the long term.
"VEGF is necessary for normal physiology," he said. "Some VEGF may be needed to revascularize the heart after ischemia or [myocardial infarction], in a small but important way. Also, there are arguments regarding maintaining the choroidal capillary bed fenestrations, and VEGF is needed to do this. Totally blocking VEGF, therefore, might theoretically prove to be disadvantageous over a longer period of time."