Should FDA Have Approved Lilly Alzheimer's Agent?

Late last week, the FDA approved an imaging agent from Eli Lilly for detecting beta-amyloid plaques in patients with cognitive impairment and who are being evaluated for Alzheimer's disease. Known as Amyvid, this is the first diagnostic agent approved for people who undergo a positron emission tomography, or PET, scan.

The approval comes after the agency last year initially declined to approve Amyvid over concerns that scans can be accurately read. An FDA advisory panel had voted against approval and noted that Lilly should first have to demonstrate that interpreting brain scans showing plaques could consistently yield an accurate diagnosis (here is the Lilly presentation to the panel).

To convince the FDA, Lilly conducted reader training for interpreting results, which the drugmaker maintains was effective and underscored the reliability of using its diagnostic tool. And the program will be available to specialists at both institutions and online, according to Edward Coleman, a professor of radiology at Duke University Medical Center, who has consulted for Lilly.

However, Coleman acknowledged that Avymid reliability was not measured in the absence of a reader training program. Nonetheless, he maintained that similar levels of reliability were recorded using both in person and online versions of the training program. "Reliability is heighted by this reader training," he said during a media briefing this morning.

In discussing the approval, Lilly was cautious to note that a positive Amyvid scan does not establish a diagnosis of Alzheimer's and that using the agent is actually an adjunct to other diagnostic evaluations. A positive scan indicating moderate to frequent amyloid plaques may be present in other types of neurological condition or older people with normal cognition (read the statement).

One critic says the FDA should not have approved Avymid. The agency "backed off, but it's a dangerous test," says Sid Wolfe, who heads Health Research Group at Public Citizen. "It's inaccurate. The advisory committee voted it down because those who didn't have Alzheimer's were read as having it and, conversely, those who did have (Alzheimer's) were negative, in some cases." (Here is a letter he wrote to the FDA last year).

"The ifs, ands and buts in the Lilly press release fail to obscure the fact that this is an inaccurate test, subject to serious inter-reader interpretation differences, that has been shown to falsely diagnose Alzheimer’s Disease in patients who do not have the disease and fail to diagnose it in patients who turn out to have the disease," he continues. "It is clearly a financial boondoggle for Lilly but another blow for Alzheimer’s patients, their families and friends."

Last year, the consumer group charged that the authors of an Avymid study published in the Journal of the American Medical Association excluded data on the extent to which the scans could be intepreted accurately from one doctor to the next (back story with links to the JAMA study and the Public Citizen letter). Lilly denied the assertions and maintained the study data was conducted and disclosed properly.

Wolfe also contends this marks the second time in two years that, in his view, the FDA has wrongly approved a product for Alzheimer’s. The other instance involved a higher dose of the Aricept pill sold by Pfizer, which was given a green light by the agency over the objections of staffers who noted the drug did not improve overall functioning, and caused more side effects than a lower dose available (back story).

Meanwhile, neither Avymid nor the accompany PET scan will be covered by Medicare, which means that Lilly will have a limited ability to recognize huge amounts of revenue from its agent. The drugmaker expects to charge $1,600 per patient ready dose on a wholesale acquisition cost basis, according to ISI Group analyst Mark Schoenebaum.

Consequently, he foresees $500 million in annual revenue. The math? Assuming about 450,000 cases of Alzheimer's diagnosed each year in the US, he estimates Lilly will win about one-third of the market, since there are other PET imaging agents, and the training program may impede uptake by some doctors. Total US sales, even assuming Medicare coverage, might be $200 million. He adds $300 million from Europe, where Lilly is seeking approval.

To overcome the lack of Medicare coverage, a Lilly spokeswoman says the drugmaker is working with such organizations as the American College of Radiology and the Society for Nuclear Medicine in hopes of convincing the Centers for Medicare & Medicaid Services to formally reconsider its policy on agents and PET scans, which has been in place since 2000.