Source: DGNews  |  Posted 8 years ago

By Earl R. Nichols

ANAHEIM, CA -- November 24, 2003 -- Ranibizumab (rhuFab), an investigational anti- vascular endothelial growth factor (VEGF), appears to increase visual acuity in patients with age-related macular degeneration (AMD), according to a study reported at the American Academy of Ophthalmology meeting held here November 15th-18th.

Jeffrey Heier, MD, Ophthalmic Consultants, Boston, Massachusetts, United States, presented the results of two Phase I/II trials that examined the safety, tolerability and biological activity of ranibizumab in individuals with the wet form of AMD.

Wet AMD is characterised by choroidal neovascularisation (CNV) -- abnormal growth of blood vessels within the macula. VEGF is thought to play a major role in inducing CNV. Ranibizumab is a recombinant humanised antibody fragment, designed to bind to and inactivate VEGF.

The first study that Dr. Heier presented was a multicentre, randomised clinical trial involving 64 patients -- some with minimally classic lesions, some with predominantly classic lesions, and some who had undergone previous photodynamic therapy (PDT), the currently accepted standard of care for wet AMD.

Patients were randomised to receive ranibizumab 300 mcg, ranibizumab 500 mcg, or usual care. In the ranibizumab groups, intravitreal injections were administered once weekly for 8 weeks. The usual-care group received injections every week for 4 weeks, with the option of remaining on usual care or crossing over to the ranibizumab group for the last 4 weeks. The study was not blinded.

According to Dr. Heier, ranibizumab was well tolerated by the 62 patients who received it. The most common adverse event was transient inflammation. There were three drug-related serious adverse events -- one case of endophthalmitis that was treated successfully; one case of recurrent uveitis that resolved; and one case of central retinal venous occlusion in an 82-year-old diabetic woman.

Patients on usual care continued to lose vision. At Day 210 they had lost the ability to discern 5 letters on the Early Treatment for Diabetic Retinopathy Study (ETDRS) chart -- the gold standard for acuity testing in clinical trials. Patients who received ranibizumab at the 300 mcg dose gained 12.8 ETDRS letters, and those receiving 500 mcg gained 15.0 letters. Patients who crossed over from usual care to ranibizumab gained 10 or more ETDRS letters by the end of the trial.

The second study examined three different dose-escalation strategies, each of which started at 300 mcg once weekly and increased to either 1.0 mg or 2.0 mg once weekly.

"When we compare visual acuity of both studies side by side, we see that 44% of patients in the latter study improved 3 lines or better compared to 45% in the first study. The large majority of patients were stable, and very few patients lost 15 letters or more," Dr. Heier said.

Across all groups, patients gained an average of 9 to 15 ETDRS letters with ranibizumab treatment.

Two phase III trials of ranibizumab are underway, one is examining patients with minimally classic lesions, the other with predominantly classic lesions.

Carmen Puliafito, MD, MBA, director, Bascom Palmer Eye Institute, Miami, Florida, United States, and lead investigator of the Macugen collaborative trial, advised delegates to be cautious of these findings.

"Both this trial and the phase II trial of Macugen showed similar percentages of gainers and stability. There are problems with interpreting the results of phase II trials, due to small numbers, patient drop-outs, and poor follow-up," he said. The phase III trials should provide a more accurate picture of the potential of this new agent, he said.

[Study title: The VEGF Antibody Approach: The rhuFab Collaborative Trial. rhuFab V2 for the Treatment of Wet AMD.]