comes with contamination risks. Very rare cases of dangerous eye infections have been reported from compounded bevacizumab, and that risk is one reason some ophthalmologists don’t prescribe the drug.
But is bevacizumab any less effective for wet AMD than the chemically similar ranibizumab, or aflibercept? That hasn’t been definitively proven. The National Institutes of Health sponsored a large study known as the Comparison of AMD Treatment Trial (CATT), to test bevacizumab and ranibizumab head to head. The NIH reported in 2012 that that there was no statistically significant difference between the two drugs on AMD patients’ vision loss after two years of treatment. Other researchers have found similar results in other studies. (For another data point, eye doctors note that aflibercept has done better in treating another retinal disease, diabetic macular edema, in head to head studies with its rivals.)
It all adds up to a segmented market. Bevacizumab has a 44 percent market share, according to a recent research note from SunTrust Robinson Humphrey. Next is aflibercept (37 percent), followed by ranibizumab (19 percent).
Polling several eye doctors, Xconomy found the same fragmentation. Carl Regillo, the director of retina service at Wills Eye Institute in Philadelphia, says he’s always preferred on-label drugs. There are “slight differences” in favor of them over bevacizumab, Regillo says, and he starts patients on either ranibizumab or aflibercept. Clark of the Palmetto Center prefers those two drugs as well. Feistmann believes bevacizumab is usually just as effective as the other drugs at a fraction of the cost. Shulman, however, will start patients on aflibercept if their AMD is particularly bad and they can get insurance coverage, feeling it’s the best drug in the group.
The high costs and increased use of eye injections have forced ophthalmologists to provide more justification for their prescriptions. Clark says he sends insurers more paperwork to support routine clinical care, but there are more denials than ever before.
In 2015, the insurer Humana instituted a “step therapy” policy for wet AMD for its commercial group and individual coverage, meaning patients have to fail or not be eligible for bevacizumab before Humana will pay for more expensive drugs. Via email, Humana spokesperson Marina Renneke said that its coverage was “consistent” with American Academy of Ophthalmology treatment guidelines and “is aligned” with National Institutes of Health research comparing the different wet AMD drugs.
The pressure from Medicare to cut costs isn’t as direct. Medicare was once able to demand a similar step therapy approach, but that ability was rescinded in 2010. In its place, doctors like Clark report more paperwork and more justification required for the expensive drugs. Direct limits aren’t completely off the table, however. The 2014 GAO report that highlighted escalating Part B drug costs spurred an outside Medicare commission to reconsider cost-saving measures, which it calls “least-costly alternative policy.” The commission has not made a final recommendation.
But a medical society for eye doctors is pushing back against the cost measures. The American Society of Retina Specialists has complained to insurers and their drug-buying agents about policy changes.
“These three anti-VEGF agents are not interchangeable,” the ASRS wrote in a December 2014 letter to Humana, arguing that specialists must be allowed to use their judgment for each patient.
Genentech and Regeneron expressed similar sentiments.
“We believe doctors choose the most appropriate medicines for their patients and having a choice of medicines is a good thing for people facing serious diseases,” said Genentech spokesperson Allison Neves.
Regeneron spokesperson Ilana Tabak says that the company “support[s] the need for a value-based reimbursement model that takes into consideration critical factors including clinical value, innovation, and cost,” but adds that the Regeneron is “committed to ensuring” that aflibercept is accessible and affordable for patients and hasn’t raised the drug’s price in the U.S. once since it was FDA approved in 2011. (Price hikes every year are common in the drug industry.)
Potential conflicts of interest also color the debate. As the New York Times and Washington Post have reported, Medicare reimbursement rules allow eye doctors to gain more financially by buying one of the on-label treatments rather than bevacizumab. And many eye doctors who were Genentech consultants were also among the top billers of the company’s ranibizumab.
Clark of the Palmetto Center in South Carolina acknowledges that he is a paid consultant to Genentech, Regeneron, and Bayer and has been an investigator in several pegpleranib trials. But he says the charge that doctors are more likely to buy and prescribe high-priced wet AMD drugs because they’ll benefit financially “isn’t fair at all.” There are tiny margins between the price his office pays for the drugs and the amount he’s reimbursed—four percent at best, he says—and he doesn’t have a low-cost, FDA-approved alternative to ranibizumab or aflibercept.
“This is an issue of drug pricing, and [retina specialists] have absolutely no control over that,” Clark says. “We just have to try to take care of people the best we can.”
It’s into this climate that combination therapy could soon arrive, with Ophthotech’s drug, pegpleranib, leading the way. The company is testing pegpleranib in three separate combinations with each of the anti-VEGF drugs. The idea is to
