The following is a guest blog post from one of our regular contributors, Alan Cassels, who is an author, journalist, and drug policy researcher with an interest in how clinical research and experience on pharmaceuticals gets translated for policy-makers, prescribers and consumers.
A March 20th story in the Boston Globe. “Biogen drug offers hope for patients with Alzheimer’s,” was one of many stories last week that cast a glimmer of hope on new drug treatment to prevent Alzheimer’s Disease, which affects as many as 5 million Americans.
Those following the ups and downs of Alzheimer’s research will recognize the feel good’ narrative of this story, where promising new pharmaceutical wizardry is once again on the cusp of a substantial advance to prevent the slow and, as yet, unpreventable slide into dementia. Unfortunately this kind of news story is not designed for health consumers, but for investors, who are lured to bet again on a winning horse, with positive signs from a clinical trial held up as bait. Surely it’s the size of the prize (a market for any Alzheimer’s drug that could actually work is potentially ginormous) that must be blinding them to the details.
Most of these stories include a few cautious caveats of the benefits and harms of the experimental treatment. It was very helpful to mention that the trial was on a “small number of patients who had early indications and mild cases of the neurodegenerative disorder,” yet the Boston Globe story wins the prize for using the most terms that Gary Schwitzer counsels journalists to strenuously avoid in health stories like “quite ecstatic”, “exceeded their expectations”, “significant breakthrough” and “in a different league.” All this from an early-stage study of 166 patients? C’mon folks, don’t treat us readers like a bunch of forgetful mice.
Anchorman Lester Holt of NBC Nightly News read his teleprompter, with a script that likened Biogen’s new drug to a “potential silver bullet to slow down memory loss.”
The Wall Street Journal joined the fray (“Biogen’s Alzheimer’s Drug Impresses in Early Trial”) adding to the enthusiasm: “While still very early, these data are more impressive than anything we’ve seen in [Alzheimer’s disease], justifying the pre-data excitement,” said Christopher Raymond, a Robert W. Baird analyst. Saying something is more impressive’ isn’t saying much at all, given how low the bar is in this field. To its credit, though, the story explained: “the so-called ‘amyloid hypothesis’ is controversial, and other drugs targeted at amyloid plaques have failed in late-stage studies.”
The New York Times reported that Biogen’s aducanumab or BIIB037, is “designed to get rid of amyloid plaque in the brain, which is widely believed to be a cause of the dementia characteristic of the disease.” Really, “Widely believed?” That’s a nose-stretcher for sure unless maybe I’ve been asleep for the last 20 years. I thought the amyloid hypothesis was soundly discredited, a perennial and embarrassing, non-starter relegated to the graveyard of potential Alzheimer’s cures. They’ve tried ultrasound, vaccines and many drugs to try to scour plaque out of our brains and nothing has even come close to finding a benefit in the human world (though to be fair, many of these treatments looked pretty good in mice). The Times did follow up with this line, though: “However, other drugs designed to prevent or eliminate plaque have failed in large clinical trials, raising questions about what role the plaque really plays.”
But those almost-afterthought followup lines from the Wall Street Journal and New York Times didn’t go far enough.
I called up Linda Furlini in Montreal, one of Canada’s experts on Alzheimer’s Disease to get her general take on this story. Following Alzheimer’s research developments for 25 years, she received a full-on education in the disease since both of her parents were diagnosed with it. She ended up doing a PhD on the subject and has served both as a volunteer and a board member for Alzheimer’s associations in Canada.
She’s seen the story of Alzheimer’s disease cured so many times, they almost trigger a yawn. “I’ve seen this stuff for 25 years and they should stop misinforming people about amyloid plaque,” she said, adding, “We don’t know if amyloid plaque is a precursor or an after-effect of the disease. Testing to get rid of it hasn’t worked for decades—so we’re beating a dead horse. We need more basic science.” That viewpoint is also reflected in a Forbes Magazine article from 2012 around the failure of another amyloid-attacking drug. It said that by the end of 2012 “we will have data from six major Phase III trials without even a shred of support for the amyloid hypothesis.” Saying that these facts are “hard to ignore,” the commentatory goes on to say that “amyloid optimism has required dismissing or minimizing the lessons of history.”
Would questioning the amyloid hypothesis (at all in some cases, or more deeply in others) have made a difference in this spate of news stories? The most quickly measurable effect of not mentioning amyloid skepticism is the fact the shares of Biogen Idec rose $42.33 to $475.98 a share, gaining about 10 percent. (Note: Biogen Idec, in the last day dropped the Idec’ from its name.)
Linda Furlini says that drug discovery hullaballoo ignores the real issues around Alzheimer’s treatment which are as urgent as ever: “Many elderly people—often seniors living at home– aren’t being diagnosed properly and are often left without the care they need.” What that means, says Ms. Furlini who quotes from a recent letter in her hometown paper, the Montreal Gazette, is that “we still have the same state of care—where the needs of those with dementia are being ignored.”
Alzheimer’s drug discovery has sadly experienced an almost universal failure rate of preclinical and Phase I, II, and III testing and nothing seems to get through the pipeline as this recent infographic from Nature Reviews Drug Discovery suggests. (The funnels illustrate the average number of compounds needed at each stage of drug development in order to get one drug approved.)
Given the millions that the United States government has already dumped into NIH-Pharma partnerships over the years testing the amyloid hypothesis (only to come up empty-handed) you’d think it would lead to a taxpayer revolt. But no, now it’s time to shakedown the British taxpayer to keep that horse alive. The Globe story concludes by saying a number of major drug companies, including Biogen are joining with “the British government and a charity to establish a $100 million venture capital fund to bankroll research into Alzheimer’s and other forms of dementia.”
Perhaps the best thing we can say about the American reporting of aducanumab is that it could be worse. See this rodent-themed story from Australia, proclaiming that a new Alzheimer’s treatment fully restores memory function. In fact, “Of the mice that received the treatment, 75 percent got their memories back.” It sounds like an article in The Onion, but it isn’t.
Beyond the inappropriate hype and failure to put these new discoveries into context, Linda Furlini and others are highly critical of the way the drug industry tries to develop preventive drugs. Unless there is any conclusive evidence that amyloid plaque is a precursor or a result of Alzheimer’s, Furlini thinks “we should stop recruiting people with mild cognitive impairment who may never develop Alzheimer’s into clinical trials with untested anti-Alzheimer drugs.”
Now that may be an idea worth banking on.
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