Low rates of ocular and nonocular adverse events were found in patients receiving either 0.3 mg or 0.5 mg of ranibizumab (Lucentis, Genentech) for neovascular age-related macular degeneration. Final 1-year results from the safety study of over 2,300 patients showed that rates of adverse events were similar to those found in other large studies of ranibizumab.
Key Biscayne, FL-Rates of ocular and nonocular serious adverse events were low in two dose groups at 1 year in a safety study of ranibizumab (Lucentis, Genentech) in patients with neovascular age-related macular degeneration (AMD).
The rates were similar to those reported in several previous studies of ranibizumab, said David Boyer, MD, a retina specialist in private practice in the Los Angeles area. Dr. Boyer presented the final 1-year results from Cohort 1 of the phase IIIb SAILOR study (Safety in Previously Treated and Newly Diagnosed Patients with Neovascular Age-related Macular Degeneration) here at the Bascom Palmer Eye Institute's 2008 Angiogenesis Meeting.
Elaborating on the results, Dr. Boyer said that a trend was seen toward higher stroke and nonvascular death rates in the 0.5 mg dose group, but it was not statistically significant. In addition, prior stroke was a significant risk factor for stroke. Although the numbers were small, a trend was seen for a higher rate in the 0.5 mg group than in the 0.3 mg group.
The individuals in that cohort were randomized 1:1 to the two dose levels of ranibizumab for three initial monthly treatments (n = 1,169, 0.3 mg, and 1,209, 0.5 mg). Re-treatments were given based on protocol-defined visual acuity (VA) and optical coherence tomography (OCT) criteria. The primary endpoint was the safety and tolerability of the drug; others were the number of adverse events, change in vision, and number of injections necessary.
"The bottom line was that the final results show that ocular and nonocular adverse events were pretty similar between the two dose groups and pretty much in line with everything we've said before," Dr. Boyer said. The outcomes were consistent with those seen in two pivotal phase III studies, MARINA and ANCHOR.
In SAILOR, patients were first randomized on the basis of having received prior treatment for AMD or being treatment-naïve. About 40% of patients were treatment-naïve and 60% had previous therapy. Patients were then randomized into dose level groups.
Clinicians then determined how to follow patients, for example basing the need for re-treatment on vision only; in that case, re-treatment would be given if a patient lost more than five letters of best-corrected VA. Alternatively, the re-treatment decision could have been made if there was an increase in central retinal thickness of more than 100 μm, or on a combination of those two criteria. About 82% of investigators chose to use both criteria, Dr. Boyer said.
Patients were given ranibizumab injections at day 0, month 1, and month 2; mandatory examinations were performed at months 3, 6, 9, and 12. The average number of injections was 4.6 over the year-long study period. Most patients received 3 to 5 injections, whereas very few had 9 to 12.
The discontinuation rate in SAILOR's Cohort 1 was 18%, which was very high compared with the rate of approximately 10% in other ranibizumab trials, Dr. Boyer said, adding that it may have been due to the protocol for re-treatment. He explained that in a typical practice setting, doctors would not wait until a patient experienced macular thickening of 100 μm before re-treating. They would more likely re-treat at a level of 50 μm. Some investigators withdrew their patients near the end of the study, believing that the re-treatment criteria were too lax and knowing that the patients could be treated with either ranibizumab or bevacizumab (Avastin, Genentech). In addition, some patients may have dropped out of the study because they were required to travel to a study center for treatment instead of being able to receive injections from local physicians.