Ranibizumab injections after PDT beneficial, interim trial finds

October 1, 2005

Montr?al—The addition of intravitreal ranibizumab (Lucentis, Genentech) has been associated with impressive efficacy for improving and stabilizing vision and reducing the need for repeat photodynamic therapy (PDT) after 12 months of follow-up in the FOCUS (RhuFab V2 Ocular Treatment Combining the Use of Visudyne to Evaluate Safety) trial, said Jeffrey S. Heier, MD, at the annual meeting of the American Society of Retina Specialists.

Montréal-The addition of intravitreal ranibizumab (Lucentis, Genentech) has been associated with impressive efficacy for improving and stabilizing vision and reducing the need for repeat photodynamic therapy (PDT) after 12 months of follow-up in the FOCUS (RhuFab V2 Ocular Treatment Combining the Use of Visudyne to Evaluate Safety) trial, said Jeffrey S. Heier, MD, at the annual meeting of the American Society of Retina Specialists.

Treatment with ranibizumab has been associated with an increased risk of severe ocular adverse events, but on average vision outcomes have been superior in those patients to those among controls treated with PDT alone. So far, there is no evidence for an increased risk of systemic adverse events associated with anti-VEGF therapy, said Dr. Heier, a private practice vitreoretinal specialist at Ophthalmic Consultants of Boston and president of the Center for Eye Research and Education Foundation in Boston.

FOCUS is a phase I/II, randomized, single-masked (patients and vision examiners were masked), multicenter, sham-controlled study.

All patients received PDT at day 0, and the ranibizumab or sham injections were administered at day 7 and then monthly thereafter. Re-treatment with PDT was performed only if leakage was noted on quarterly fluorescein angiography studies.

The two treatment groups were well matched in their baseline and demographic characteristics, and follow-up to 12 months is greater than 90% in both treatment arms. In the primary efficacy analysis of the proportion of patients with less than 15 ETDRS letters lost at month 12 versus baseline, there was a highly statistically significant difference favoring ranibizumab plus PDT versus PDT alone, 90.5% versus 68%, respectively.

A secondary efficacy endpoint considered patients gaining 15 letters or more. In that analysis, the combination treatment outperformed PDT alone by fivefold as rates of "3-line or more gainers" in the two groups were 24% and 5%, respectively.

"Many of us have frequently expressed that simply minimizing the amount of vision loss is important, but it is true vision stabilization with potential for improvement that really seems to be the more desirable objective," Dr. Heier said.

Gain in visual acuity

Analysis of mean VA change over time showed a loss of 8.2 letters among patients treated with PDT alone compared with a mean gain of nearly 5 letters in the ranibizumab combination group. Severe vision loss (30 letters or more) occurred in only 1% of patients in the combination group versus 9% of those treated with PDT alone.

Treatment with ranibizumab was also associated with a dramatic decrease over time in the need for further PDT treatments. At 3 months, only 16% of patients in the ranibizumab combination group required PDT re-treatment versus 80% of those treated with PDT alone. At months 6 and 9, there was almost a 10-fold difference in the need for PDT between the two treatment groups, and an almost 20-fold difference at 12 months. The mean number of PDT treatments administered over the 12 months was 3.4 in the PDT-only group and 1.3 in the combination arm.

"Keep in mind that the latter value includes the mandatory PDT treatment at day 0 of the trial," Dr. Heier said.

Patients who had been treated previously with PDT were allowed to enter the study, and subgroup analyses showed differences favoring the combination treatment in patients who had prior PDT.

The safety review of ocular serious adverse events showed a 5% rate of presumed endophthalmitis in the combination treatment group, representing two patients who were reported by the investigator to have endophthalmitis and three patients who were reported as having uveitis but received intravitreal antibiotic treatment.