Saturday, May 21, 2011

AMD Drug Study Sparks Concerns

The study that put bevacizumab (Avastin) and ranibizumab (Lucentis) into a dead heat for treating "wet" age-related macular degeneration (AMD) did not assure that the pricier drug would be out of contention or that the lower-cost one is a winner. In fact, the American Academy of Ophthalmology (AAO) reacted cautiously to the study, which was released Thursday.
Although the yearlong, head-to-head trial found that the two drugs were essentially equal in their effects on visual acuity, ranibizumab showed an advantage for one surrogate efficacy endpoint and in the rate of serious systemic adverse effects.
But because bevacizumab's price tag is about 40 times lower than that of ranibizumab for intravitreal dosing, many ophthalmologists have already been recommending the less expensive drug.
A finding of clinical equivalence in the closely watched 1,200-patient trial, sponsored by the National Eye Institute and conducted by the Comparison of AMD Treatment Trials (CATT) group, has been expected to tip even more physicians and patients toward bevacizumab.
Nevertheless, an official statement from the AAO stopped well short of suggesting that clinicians should prefer bevacizumab.
"The initial results of the CATT study affirm the position of the American Academy of Ophthalmology that both Lucentis and Avastin should be available for the treatment of AMD," the statement said.
"The treatment plan must be selected by the ophthalmologist and the patient, taking into account a host of complex factors," it went on.
An AAO spokesman explained that although there was no meaningful difference between the drugs in the study, ranibizumab should continue to be available to patients -- and that means retaining coverage by third-party payers.
"We want to have the choice," said Pravin Dugel, MD, of Retinal Consultants of Arizona in Phoenix and an AAO committee member.
Dugel pointed out that the CATT study reported only one year of data. "We don't know what results are going to come out next year or the year after. ... We are still in the infancy of understanding how these drugs affect blood vessels."
Although he called himself "primarily an Avastin user," he said there was widespread concern that health insurers and perhaps Medicare would drop coverage of ranibizumab because of the CATT results.
Dugel said loss of patient access to the more expensive drug could be a mistake. "No one would tell you that one-year results are decisive," he said.
Still, a recent study indicated that 55% of patients receiving a biologic treatment for AMD under Medicare were treated with bevacizumab.
Meanwhile, the manufacturer of both drugs, Genentech, insisted that ranibizumab should remain the first choice for treating wet AMD.
A statement from the company pointed to the higher rate of serious systemic adverse events with bevacizumab (HR 1.29, 95% CI 1.01 to 1.66, after adjusting for demographics and comorbidities at baseline) and ranibizumab's shorter lifetime in circulation as important advantages.
"Lucentis has been rigorously studied in 18 completed clinical trials, that included more than 7,100 patients to establish its efficacy and safety profile," Genentech said.
"It has been approved for use in the eye by health authorities worldwide. Avastin is not manufactured or approved for use in the eye. It was specifically designed and approved for the treatment of patients with certain forms of cancer."
As a result, the statement said, "we continue to believe that Lucentis is the most appropriate treatment for wet AMD."
But Dugel dismissed those differences in the trial as probably "statistical noise."
He pointed out that the increase in serious adverse effects in bevacizumab patients was concentrated in a group that received the drug "as needed" -- only when retinal imaging showed active neovascularization -- rather than those getting it on a fixed monthly schedule.
The as-needed group received cumulative doses that were about 35% lower than in the monthly treatment group.
Dugel said that, if the adverse events were truly drug-related, they ought to be more common in patients receiving more of the drug.

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