Avastin Use in Eyes Irks Genentech

Beverly Hills eye specialist Edgar Thomas swabbed his patient’s eye with anesthetic and reached for a syringe. “Now hold very still for me,” he told Cecilia Blackfield, as he inserted the needle into the corner of the 90-year-old woman’s right eye.

The syringe contained Avastin, a Genentech Inc. drug approved to treat advanced cases of colon cancer. But in the last several months, eye specialists have been using Avastin for macular degeneration, a disease associated with aging that can lead to blindness.

Blackfield, already blind in her left eye, was losing sight in the other before she received her first Avastin shot from Thomas in mid-August. Her vision was so improved weeks later that she could resume one of her favorite pastimes: reading “trashy” western and romance novels. She returned to Thomas last week for a second shot because the effects of her first treatment had started to wear off.

“This new medication is a wonderful thing,” Blackfield said as she sat under a bright light in an examination room before receiving her shot. “I can’t live without a book. Not to read, it’s horrible.”

Although “off-label” drug use -- using a drug for other than its government-approved purpose -- often boosts sales, Genentech is not happy to see eye specialists experimenting with Avastin. The South San Francisco-based biotechnology giant has been developing another drug, Lucentis, for macular degeneration. But according to eye specialists who’ve used Avastin, the cancer drug appears as effective as Lucentis -- at a fraction of the cost.

So far, evidence that Avastin works is largely anecdotal. The American Academy of Ophthalmology has called for clinical trials of Avastin, but Genentech said it had no plans to support human tests in eye patients.

“We have one drug that is proven after six years of very careful clinical trials conducted to high standards,” Genentech President Susan Desmond-Hellman said, referring to Lucentis. “We don’t think there is a benefit to patients to go back” and look at Avastin.

More than 1,000 patients with macular degeneration have been treated with Avastin, according to stock analysts and eye specialists. The annual meeting of the ophthalmology academy in Chicago over the weekend was abuzz about Avastin, according to people there.

Some analysts have reduced their earnings forecasts for Lucentis, which is expected to reach the market next year. Eric Schmidt of SG Cowan & Co. estimated that nearly half of Lucentis’ anticipated sales of $1.1 billion could instead go to the cancer drug.

Lucentis is a fragment of Avastin, a genetically engineered antibody. Both drugs block a protein that causes abnormal blood vessels to grow. In cancer, new blood vessels feed tumors. In macular degeneration, vessels proliferate behind the eye and damage the retina, causing vision loss. About 200,000 people in the U.S., most of them elderly, have the most serious form of the disease.

Avastin is an expensive treatment for colon cancer, costing $4,400 a month, because patients require large amounts of the drug. A tiny amount of Avastin is needed to treat macular degeneration, so the price is much lower, about $5 an injection. Because of a markup by the pharmacy, which must package Avastin into vials, the cost of an injection ends up ranging from $35 to $75. Avastin shots are given every two to four months.

Existing drugs for macular degeneration cost significantly more. Macugen, a drug marketed by Pfizer Inc. and Eyetech Pharmaceuticals Inc., goes for $995 an injection. Genentech hasn’t yet set a price for Lucentis, but analysts expect it will cost more than Macugen because the Genentech drug appears to be more effective.

Genentech said it started work on Lucentis in the late 1990s after its research indicated that Avastin wouldn’t work in the eye. Two animal studies -- including one that was published -- suggested that a large antibody like Avastin could not penetrate the retina to reach the troublesome blood vessels behind the eye, the company said.

But some eye specialists say Genentech’s research was far from conclusive because the company did not experiment with Avastin itself. One study looked at Herceptin, a breast cancer drug, and the unpublished experiment used an early version of Avastin.

“They never studied Avastin,” said Dr. Philip Rosenfeld, who has given the drug to 250 patients at the University of Miami’s Bascom Palmer Eye Institute. “There was no evidence that it would or would not work.”

Genentech defended its research, saying Avastin was not available when the company performed its tests.

“I am very comfortable with how we went about it,” Desmond-Hellman said. The experiments were based on “sound drug principles” and knowledge of “how antibodies work.”

The executive said Lucentis was designed for use in the eye and was 10 times more potent than Avastin. She said the drug did not contain a preservative and that breaking down Genentech’s packaging to create the doses increased the risk of contamination. Eye specialists and stock analysts, however, said they knew of no infections related to Avastin.

Genentech is in discussions with the Food and Drug Administration to modify the Avastin label to state that the drug is not for ophthalmic use -- language that could discourage some eye specialists from using the medicine. In addition, Genentech is preparing to offer Lucentis at no charge to 5,000 patients as part of an expanded access program that will continue until the drug receives FDA approval.

But analysts and eye specialists doubted the trial would blunt enthusiasm for Avastin. At a medical meeting in San Diego last month, 80% of 250 ophthalmologists in attendance said they planned to use Avastin in the coming months, said University of Iowa eye specialist James Folk, who writes a blog on eye disorders and treatment.

Avastin started catching on in July, after Rosenfeld presented results of a single case at a medical meeting in Montreal. Rosenfeld said the patient’s vision improved after an Avastin injection -- on a par with outcomes seen in Lucentis trials. Rosenfeld said he started experimenting with Avastin because approved treatments weren’t helping his patients. “They were going blind,” he said.

His result led other specialists to experiment. Thomas has given Avastin to 50 patients since August, and all have gained vision, he said. Blackfield was his first Avastin patient. Two weeks after she received the drug, her right eye improved to 20/40 from 20/200, which is the definition of legal blindness.

“We don’t have many drugs that make you say, ‘Wow.’ But this is a wow drug,” Thomas said.

Not all eye specialists have embraced Avastin. Joan Miller, head of ophthalmology at Harvard Medical School, said the side effects of using Avastin in the eye weren’t known. She noted that cancer patients who took Avastin developed high blood pressure, a particular problem with the elderly.

“All this switching to Avastin, when it hasn’t even been tested in animals, is a little startling to me,” she said.

Rosenfeld said he was developing plans for a large clinical study that would compare two Avastin doses, and hoped to gain the federal Medicare agency’s support. Rosenfeld said he believed that Avastin might be a longer-acting drug than Lucentis, which could spare patients some shots, and he was eager to test the drugs head to head.

“This is how capitalism is supposed to work,” Rosenfeld said. “This could save Medicare billions.”