Monday, March 27, 2006


Jennifer Webb, writing in the February 15th issue of Ophthalmology Times, reported that George A. Williams, MD, a vitreoretinal specialist in private practice in Royal Oak, MI, and chairman of the department of ophthalmology at William Beaumont Hospital, speaking at Macula 2006 in New York City in January, said that, “Ophthalmologists who choose to use bevacizumab (Avastin, Genentech) for off-label treatment of wet age-related macular degeneration (AMD) should not expect Medicare to reimburse those expenses.”

When he polled the 300 attendees at the meeting, on whether they had tried Avastin, “Ninety percent of the hands went up. I've never seen anything like this in 25 years of medicine: how quickly this has permeated the field and how quickly it's being adopted."

In a Dec. 21 article posted on Medscape, Jennifer I.. Lim, MD, explained that bevacizumab offered symptomatic relief from active subfoveal choroidal neovascularization (CNV) in a high percentage of patients, and its intra-vitreal use has increased "exponentially" in the past few months.

"Positive presentations at retinal meetings and the two published case reports of visual acuity improvement and decreased retinal thickness have led the retinal community to embrace this new treatment," Dr. Lim wrote. She is associate professor of ophthalmology, University of Southern California, and medical director of clinical trials, Doheny Eye Institute, Los Angeles.

Weighing off-label use

Despite this interest over bevacizumab, insurance carriers and Medicare are not as enthusiastic. Aetna, for example, listed the drug in late November as experimental and investigational—and not medically necessary—for the treatment of AMD.

"Carriers decide whether they're going to cover an off-label use based on a variety of evidence such as published trials, clinical trials, and published reports. [Bevacizumab] has moved so quickly [that] we still don't have publications out," Dr. Lim said. "Until they see these publications, their decision will be they can't cover it."

William Rich III, MD, medical director of health policy for the American Academy of Ophthalmology (AAO), said many accepted procedures and treatments are used off-label. He cited the National Institutes of Health-sponsored clinical trials that recommend injection of intravitreal antibiotics to treat endophthalmitis as one example.

Dr. Rich said bevacizumab is an appropriate drug to use as "salvage therapy" after other treatments have failed. Although Medicare does not yet reimburse for bevacizumab therapy for AMD, most patients are willing to pay the cost, Dr. Rich said. The drug costs $20 to $80 per treatment, he said.

However, two reports on the safety and efficacy of bevacizumab injections are expected to be published soon, he said. After that happens, AAO leaders and retina specialists will ask the Centers for Medicare and Medicaid Services to cover those treatments, as it does for off-label use of triamcinolone to decrease the need for photodynamic therapy and uveitis injections around the eye.

"There's not enough literature to justify [covering the] treatment at this time," Dr. Rich said, adding that the AAO also supports a head-to-head comparison of bevacizumab and ranibizumab (Lucentis, Genentech).

"Once a treatment is approved, physicians can use it and prescribe it how they see fit," said Genentech spokeswoman Dawn Kalmar. However, she said, "we are concerned, because we specifically designed ranibizumab to avoid some of those things that may or may not happen with a full-length antibody such as bevacizumab. The company has never performed any trials, animal testing, or toxicity testing using bevacizumab in this manner, so it is "concerned."

"From our perspective, that points to a significant unmet need that's still out there," Kalmar said. "People are willing to try it because there really is no hope for many of these patients. Our primary stance is: we're doing everything we can to get ranibizumab into the hands of physicians and patients as soon as possible."

For example, the company filed Dec. 30 for priority review status for ranibizumab with the FDA. Kalmar said Genentech should know within 6 weeks of that date if that status is granted. Once prior review status is achieved, Genentech would hope to have approval for the drug later this year.

She also pointed to the opening of a phase IIIb, single-masked, 1-year multicenter study of the safety and tolerability of intravitreally administered ranibizumab in patients with active subfoveal choroidal neovascularization (CNV) secondary to AMD. The trial, which began in November 2005, will enroll 5,000 patients at 70 sites nationwide, giving physicians an opportunity to try the new drug before FDA approval, she said.

As a full-fragment antibody, bevacizumab might not penetrate as well as researchers believe ranibizumab will, she added.

"When we tested a full-length antibody, it didn't penetrate as readily to get to the root cause of where the disease was," Kalmar continued. "One of the reasons we did a small fragment [version] was to penetrate to all the layers of the retina to get to where the disease starts."

When the most recent ranibizumab data were presented at the Macula 2006 meeting, "I literally saw jaws drop," she added. "We're very pleased both on the efficacy and safety side of ranibizumab and we're looking forward to getting it out there."

Author’s Note on Avastin

Since the original posting on January 31st, I have added three updates on this important drug for treating age-related macular degeneration. In addition to the posting you are reading, here is a listing (with links) to the others:

Avastin: A New Hope for Treating AMD

Avistin Update II: AAO supports Medicare Coverage for Off-label Avistan Use

ARVO 2006: A Further Update on Both Avastin and Lucentis for Treating AMD


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