Neil Osterweil

May 03, 2011

May 3, 2011 (Fort Lauderdale, Florida) — Two-year data from a study pitting bevacizumab (Avastin, Genentech) against ranibizumab (Lucentis, Genentech) for treating neovascular or "wet" age-related macular degeneration (AMD) confirm what the 1-year data showed: Bevacizumab is generally comparable in safety to its 40-fold more expensive cousin ranibizumab. The data were reported by the study's investigators here at the Association for Research in Vision and Ophthalmology (ARVO) 2011 Annual Meeting.

As Medscape Medical News reported earlier, 1-year data from the Comparisons of Age-Related Macular Degeneration Treatments Trials (CATT) showed no significant differences between the 2 angiogenesis inhibitors in their ability to improve visual acuity in all but 1 safety parameter when administered on either a monthly or as-needed basis (PRN) in patients with neovascular AMD. These data were published online in The New England Journal of Medicine.

"For the last 5 years, ophthalmologists and patients have been confronted with the choice every day: What to do and how often. These results inform our decision, which was our primary goal," said lead author Daniel Martin, MD, from the Cleveland Clinic Cole Eye Institute in Ohio.

"Lucentis and Avastin were equivalent — in fact, virtually identical for visual acuity at all time points — when administered in the same dosing regimen," Dr. Martin said.

Asked whether he were to recommend 1 drug over the other for a family member newly diagnosed with AMD, Dr. Martin said that "I still believe that it is a choice for the patient. If they leave it completely to me, I do not believe there is any difference between Avastin and Lucentis. I have seen nothing so far regarding adverse events that would concern me greatly, and I would probably start with Avastin."

PRN Dosing: Diligence Due

The results with PRN dosing, although not quite as good as those seen with monthly dosing (an average of 2 letters less gained), were still excellent — "the best that's ever been achieved," according to Dr. Martin. This was as result of diligent monthly follow-up. PRN dosing results in 4 to 5 fewer injections over 1 year than monthly dosing, and both drugs produced an immediate and substantial decrease in fluid, although neither drug was able to eliminate fluid in the majority of eyes.

Bevacizumab is approved for various forms of cancer, and ranibizumab is approved for treatment of wet AMD. Both are delivered via injection into the vitreous humor. Bevacizumab costs about $50 per dose, ranibizumab about $2000. The molecularly similar drugs are both made by the same manufacturer, which has reported that it is not pursuing an AMD indication for bevacizumab.

Genentech Responds

In a statement released to coincide with the publication of the 1-year results in The New England Journal of Medicine, Genentech said that "Avastin and Lucentis are different medicines. We specifically designed Lucentis to be cleared more quickly from the bloodstream to minimize side effects. "

The statement also noted that "these findings from CATT add to an emerging body of evidence from much larger analyses that suggest the risk of systemic adverse events may be higher when injecting Avastin into a person's eye compared to Lucentis."

According to Paul Sieving, MD, PhD, director of the National Eye Institute of the National Institutes of Health in Bethesda, Maryland, sponsor of the CATT study, most of the 250,000 Americans treated for neovascular AMD with an angiogenesis inhibitor each year receive off-label bevacizumab.

Safety Data at 1 and 2 years

One-year data from the study showed that rates of death, myocardial infarction, and stroke were similar for patients receiving either drug, although bevacizumab was associated with a 24.1% rate of serious systemic adverse events (primarily hospitalizations) compared with 19% for ranibizumab (risk ratio [RR], 1.29; 95% confidence interval [CI], 1.01 - 1.66).

As Dr. Martin reported here, rates of death from any cause were essentially unchanged from 1 to 2 years, at 1.5% vs 2.8% among 599 patients receiving ranibizumab and 2.6% vs 2.9% among patients receiving bevaciumab. There were no significant differences between the drug groups in overall death rates at 2 years (P = .42).

Arteriothrombotic events were identical among patients receiving ranibizumab at years 1 and 2 (2.2% each year) and went down slightly from 1 year to the next among patients receiving bevacizumab (2.4 vs 1.7%). Strokes occurred in 0.8% of patients receiving ranibizumab at year 1 and 1.2% during year 2, and in 1.2% of patients receiving bevacizumab each study year.

At baseline, patients in both the bevacizumab monthly and PRN groups had more hypertension, diabetes, smoking, and conditions such as congestive heart failure, history of myocardial infarction, or arrhythmias than patients receiving ranizumab, Dr. Martin noted.

It remains to be seen whether visual acuity gains seen at 1 year will be continued through 2 years, the authors noted.

The CATT trial was supported by the National Eye Institute. Coauthor Juan Grunwald, MD, reported receiving consulting fees from GlaxoSmithKline, and coauthor Glenn Jaffe, MD, reported receiving consulting fees from Neurotech and SurModics. The remaining authors have disclosed no relevant financial relationships.

Association for Research in Vision and Ophthalmology (ARVO) 2011 Annual Meeting: Special presentation. Presented May 1, 2011.

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