Competing Eye Care, Big Price Difference

One drug, Lucentis, costs $2,000 a dose.

The other, Avastin, costs $40 a dose.

Yet according to an initial small-scale study led by Manju Subramanian, an assistant professor of ophthalmology at Boston University’s School of Medicine, both drugs seem to work the same medical wonder: they help victims of “wet” macular degeneration, the leading cause of blindness among older Americans, to see again.

Subramanian’s findings should be great news not only for those suffering from macular degeneration, but for Genentech, the San Francisco–based pharmaceutical giant that produces Avastin, which is approved by the Food and Drug Administration to treat cancer, but not macular degeneration. But the company does not seem eager to embrace or endorse the findings.

That might be because it also owns and markets Lucentis.

“If Lucentis didn’t exist,” Subramanian says, “Genentech likely would have been overjoyed to have a colorectal cancer drug turn out to be a treatment for macular degeneration, but in this case, the off-label use is competing with their own product.”

Subramanian’s study, created with support from the VA Boston Healthcare System, Jamaica Plain Campus (Boston’s Veterans Affairs hospital), and now in its ninth clinical month, is emerging evidence that Genentech’s more expensive drug is no more effective against macular degeneration than its lower-priced drug. Her results, set to be reported at a conference sponsored by Ocular Surgery News in Hawaii beginning January 17, seem positioned to do two things: help answer a specific medical question that could save consumers millions of dollars and highlight a serious, systemic problem in the way drug efficacy studies are funded.

A large-scale clinical trial sponsored by the National Eye Institute also is under way, without Genentech involvement, and findings are expected in 2011.

Genentech has refused to fund head-to-head studies that compare the two drugs. “I believe they didn’t want to know the answer,” says Subramanian.

Genentech disagrees.

“From our perspective,” says spokesperson Nikky Levy, “Lucentis is approved by the FDA and meets the need of patients with wet, age-related macular degeneration, so our resources are better spent identifying new medical needs.” She would not address financial specifics about the two drugs or how Genentech’s bottom line would be affected if Avastin replaced Lucentis as the approved drug of choice for people with macular degeneration.

The notion that Avastin, first brought on the market in 2004 to treat colorectal cancer, might also help with one type of macular degeneration is not as strange as it seems. The drugs share a molecule and a mission: both inhibit blood cell development in ways that can starve a tumor and stop blood leaking into the eyes, which causes loss of sight.

Lucentis was approved for eye use in 2006, and Subramanian says the results have been “amazing. Before that, the best we could hope for was to stabilize vision,” using laser treatments to cauterize tiny veins in the eye and try to stop further leakage. “This is the first drug that actually stabilizes and improves vision.”

Philip Rosenfeld, a professor of ophthalmology at the University of Miami, first made the observation that some patients who were taking Avastin were also recovering sight. “It was a eureka moment,” says Subramanian, but initial studies suggested that “side effects from getting Avastin through the vein to treat the eye were too great.” And so came the natural next question: could Avastin be injected into the eye, like Lucentis, and be just as helpful?

“Retina specialists all over the world called for Genentech to sponsor a head-to-head trial,” she says.

Genentech refused, and many conjectured that the motive for the decision was profit-based. When Avastin came on the market to treat cancer in 2004, a price was established; ditto for Lucentis in 2006. Because only tiny amounts of Avastin are needed in eye care as compared to cancer treatment, the price per dose becomes far smaller: for the recommended regime of 13 injections a year, a patient, or insurance company, would pay approximately $26,000 for Lucentis, but only about $650 for Avastin. That shift would have huge implications for the company; Genentech reported $875 million in sales for Lucentis in 2008, although Avastin remains its most popular drug, with almost $2.7 billion in sales the same year.

Meanwhile, even though it is not FDA-approved for eye care, retina specialists have begun using Avastin, in what is called an off-label application: once a drug is approved by the FDA for one use, physicians have the right to prescribe it for another malady. “At professional meetings, more than half the people present raise their hands when asked if they are using Avastin,” says Subramanian. “Because of the cost difference, in most Third World countries they’re using it.”

Yet even if a doctor believes the drugs work equally well, “what if a veteran attending a VA hospital wants the FDA-approved drug?” asks Subramanian. “You shouldn’t deny them that — it’s not ethical.”

That question helped persuade the Boston VA Healthcare System to help fund Subramanian’s initial studies and locate patients. Recruitment was slower than she’d hoped; she found 29 patients who fit all her criteria. Of that group, she expects only 22 or 23 to complete a full year of comparison.

At the six-month mark, Subramanian found “no difference in efficacy” between the two drugs, using the rigorous criteria of a double-masked, randomized, controlled trial. But the trial pool is too small for conclusive proof — about 125 patients are needed to claim scientific validity.

Generally, drug companies support clinical trials as the only way to get their new products into the marketplace. Despite the funding source, such studies supposedly are structured to be unbiased, with careful peer review. In this case, apparently because of the level of controversy and the money involved, the National Eye Institute, under the umbrella of the National Institutes of Health, stepped in.

Genentech’s Levy insists that the company’s position is driven by safety concerns. “There are different standards for drugs that are being injected into the eye” than into veins, she says, and that could affect patient health. In addition, Lucentis works using “a smaller molecule, which can penetrate the retina better.”

Subramanian’s initial outcome suggests otherwise. But until larger-scale studies either support or disprove her findings, the status quo remains in effect. And there is no need for double-masked, randomized trials to conclude that the status quo improves Genentech’s bottom line.

Seth Rolbein can be reached at srolbein@bu.edu.