A hint of success in treating Alzheimer’s raises ethical quandary

This post has been corrected. See note at the bottom for details.

Amid the generally discouraging news about drugs that can slow or reverse the progress of Alzheimer’s disease, a new study is a faint glimmer of hope: In mice whose brains are clogged with the protein deposits that characterize Alzheimer’s, a drug called bexarotene substantially reversed key signs of dementia and reduced by half the telltale protein deposits of the disease.

The encouraging new findings come at a heartbreaking moment: just two days after a pair of pharmaceutical giants announced they are abandoning further work on bapineuzumab, an immunotherapy for Alzheimer’s disease that proved disappointing in the late stages of human testing.

By contrast, bexarotene, known commercially as Targretin, is already on the U.S. market, approved by the Food and Drug Administration as a treatment for a form of non-Hodgkins lymphoma that affects the skin. And that has led a trio of bioethicists from the National Institutes of Health to ask: What’s to stop a physician from prescribing bexarotene to an Alzheimer’s patient whose family believes it’s their loved one’s only hope?

Legally, the answer is: nothing. Because bexarotene is already legally available in the U.S., physicians are perfectly entitled to use their medical judgment and prescribe the drug “off-label” to their patients.

Ethically, however, the team of bioethicists says that the latest study poses a difficult conundrum -- as have similar situations where early evidence suggests an existing medication may help treat an incurable disease.

The latest study, and the accompanying perspective, were published Thursday in the New England Journal of Medicine. And the ethicists’ concerns couldn’t come too soon: There’s already plenty of evidence that patients’ families are clamoring to get bexarotene, on the basis of research published last February.

For starters, the ethicists note that the results of the new research are a far cry from proof that bexarotene will have the same dramatic effects in the human brain, or on human behavior. The drug’s side effects can be significant, they add: It can raise cholesterol, reduce the effectiveness of insulin in diabetics, and it’s been linked to changes in thyroid function, acute pancreatitis and low white blood-cell count.

Those facts alone dictate that it is too early for a physician ethically to prescribe bexarotene for Alzheimer’s disease. But even if further trials on humans are promising -- a circumstance the ethicists say would likely create “sudden overwhelming demand” for the drug -- the dilemma faced by physicians, patients and their advocates may persist.

For one thing, widespread use of the drug among Alzheimer’s disease patients may make it more difficult for researchers to populate the clinical trails needed to rigorously test the drug’s effectiveness in treating the disease. Those will require that some subjects get a placebo -- and if bexarotene is already in wide use, many families will shy away from enrolling a loved one in a clinical trial, fearing they might not get the drug.

Second, patients and their advocates must consider whether it is fair for doctors to begin writing prescriptions for bexarotene for patients with dementia. The estimated out-of-pocket cost of bexarotene per month is $1,200 to $2,500. The unreimbursed cost of treating an Alzheimer’s disease patient with bexarotene would make this a treatment option only for the very wealthy. And to the extent that Alzheimer’s patients would likely quickly deplete stores of bexarotene, the far smaller population of lymphoma patients who need the drug would likely be unable to find it.

Physicians’ groups “should not try to address this challenge alone,” wrote the bioethicists, led by Dr. Steven B. Pearson of the National Human Genome Research Institute. Similar ethical concerns came up when drugs that would treat HIV/AIDS first came to light, they wrote. And they will continue to arise as research finds new uses for old drugs.

“It would be crucial ... to engage with a broad spectrum of patient advocates and others to produce guidance with true legitimacy,” the authors wrote. “Such a discussion could provide a model for future situiations with other therapies,” they added.

[For the record, 12.35 p.m. Aug. 13: An earlier version of this post incorrectly said that the out-of-pocket cost of bexarotene is $1,200 to $2,500 per day.]