A Giveaway to Big Pharma

For brief descriptions of and links to recent posts, click here. For an inverse-chronological list with links to all posts after January 23, 2017, click here. For a subject-matter index to posts before that date, click here.

If you seek evidence of our political leaders abandoning science to serve our Oligarchs and the public’s wishful thinking, you need look no further than the FDA’s approval of a new drug for Alzheimer’s disease.

The new drug is made by Biogen, Inc. It has the generic name Aducanumab and the trade-name Aduhelm. The FDA just granted it accelerated approval, subject to a requirement for additional trials, which, according to the New York Times, could take years.

Before we start following the money and wishful thinking, let’s explore four key facts about this new drug. First, the primary reason for its accelerated approval was its ability to reduce the famous amyloid plaques in the brains of Alzheimer’s patients. As an FDA doctor wrote on the agency’s website, the “FDA has determined that there is substantial evidence that Aduhelm reduces amyloid beta plaques in the brain and that the reduction . . . is reasonably likely to predict important benefits to patients.” (emphasis added.) In other words, there was no solid proof, just hope.

In fact, the FDA’s own scientific advisory committee recommended against approving this drug. One of its members took the extraordinary step of publishing, with another expert co-author, an op-ed piece in the New York Times explaining why. As the Times also reported separately, “Prominent experts, including the F.D.A.’s independent advisory committee and a professional society representing geriatricians and other health care providers for older adults, urged the agency not to approve the drug.”

The second important thing to understand is the role of the famous amyloid beta plaques in the disease itself. Science simply doesn’t know what that role is. The plaques appear reliably in the brains of Alzheimer’s patients and appear to get denser and more tangled the worse the disease. But whether they are the cause of the disease, or whether they are just a highly visible chemical symptom, is simply unknown.

Amyloid plaques are not like the fatty plaques in coronary arteries that signal heart disease. The adverse effects of those plaques is simple, mechanical and obvious: they block the flow of blood. But the brain and its neurons are far more complex than blood vessels. There is no medical analogy between the two types of plaques, apart from the verbal coincidence of using the same English word to describe them. For all science knows now, reducing amyloid plaques in Alzheimer’s patients might do as little good for symptoms as reducing the fat around a heart patient’s midriff without reducing the plaques in his coronary arteries.

That sad fact is that science knows little about the microbiology and genetics of Alzheimer’s disease. We do know it tends to run in families, especially early Alzheimer’s. But science has identified neither the precise genetic pathway nor the microbiological mechanism(s) of the disease. There may be several. Humans’ natural blood-brain barrier makes its hard to study brain function in live patients, let alone at a microbiological/chemical level. And studying the progression of such a complex disease by autopsy is obviously not easy.

So instead of running down the basic science, i.e., microbiology, most industrial research has been chasing the “holy grail” of reducing the plaques. It has just assumed that the plaques are the cause, without researching in depth or knowing the truth. All this comes at time when decades of basic microbiological/genetic research allowed two industrial companies (Pfizer and Moderna) to develop outstandingly effective vaccines against Covid-19 in less than a year.

The third thing to know about Aduhelm is that it’s not the first drug able to reduce the plaques. As the New York Times explained, “Over more than two decades of clinical trials, many amyloid-reducing drugs failed to address symptoms, a history that, some experts say, made it especially important that aducanumab’s data be convincing.” (emphasis added). Approving Aduhelm under this circumstance seems to fit Albert Einstein’s definition of insanity: doing the same thing over and over again and expecting different results. What we need is aggressive funding of basic research to understand what causes Alzheimer’s, what genes promote it and how.

The final thing to understand about Aduhelm is its side effects. In two Phase 3 clinical trials, only one—with a higher dose—showed measurable improvement in symptoms. The higher dose “could delay cognitive decline by 22 percent or about four months over 18 months.” But in that trial an astonishing forty percent (that’s two fifths) of patients showed brain swelling and/or bleeding, which can often be detected only by expensive MRIs. (Only 6% of patients had severe enough symptoms to force them to quit the trials.) In contrast, the reported incidence of severe side effects (over 104 °F fever) after the second shot of Pfizer’s Covid-19 vaccine was two out of 2098 + 1660, or 0.05% [Search for “Systemic Reactions”].

I’m an ex-scientist (Ph.D., physics, 1971 UCSD) and a world-class hypochondriac. My mother died of Alzheimer’s, so I probably have at least some of the genes. I’m almost 76 and could be starting to develop the disease. Would I take Aduhelm based on this information? Absolutely not. In fact, I probably won’t take any Alzheimer’s drug until someone proves a cause and effect relationship between what it does and Alzheimer’s. The precise role of amyloid beta plaques is still unproven and mostly unknown; holy grails, I believe, are for religion, not science.

So why the hasty approval? To answer that question, we must leave the realm of science and follow the money and the wishful thinking. According to the New York Times, Biogen intends to charge $56,000 per patient per year for Aduhelm. There are about six million patients in the US and an estimated 30 million worldwide. If a mere ten percent of them take the drug, that’s $33.6 billion in annual revenue for Biogen, just inside the US. Worldwide, it’s $168 billion annually. Most of the domestic haul would probably come from Medicare, i.e., the US government. In comparison, the US government reportedly spent approximately $2.5 billion to develop and buy doses of the Moderna Covid vaccine, and $1.95 billion to buy doses of the Pfizer Covid vaccine, whose development was privately financed.

This huge expense is for a drug that reduces plaques never proven to cause Alzheimer’s, whose effect on symptoms is ambiguous and uncertain, and which causes serious side effects in 40% of those who take it. But that’s not all. The MRIs needed to monitor those side effects are expensive and will provide a bonanza for diagnostic imaging companies, whether or not related to Biogen. So perhaps the best argument for approval is that it’s a private stimulus bill for Biogen and the diagnostic companies that do Alzheimer’s-related brain imaging and test memory and cognitive function.

But that’s still not all. There are also so-called “patient advocacy groups” that pushed hard for approval of Aduhelm. The expert op-ed author who advocated not approving the drug yet and the New York Times both mentioned them, without much information about them.

It’s an unfortunate truth about our society that virtually everything has become political. But activists don’t do scientific or medical research; most of them don’t have the training, let alone the specific knowledge.

So it’s OK for activists to push for experts to do the work and for the government to fund it. That’s in fact what most AIDS activists did back in the day. Quite rightly, they pushed back against the Reagan Administration’s refusal to even mention the disease, or to fund research into it, apparently because most of the people suffering and dying were gay.

But it’s quite another thing for activists to push for approval or marketing of a particular alleged cure when the experts are skeptical or opposed. Then politicians’ favor is little more than pandering. Pandering can come back to bite everyone, including patients, if preliminary warnings of ineffectiveness and/or dangerous side effects prove prescient. Imagine how shamed our FDA will be if, five years or so down the road, real understanding of Alzheimer’s disease produces a preventative as effective as today’s Covid vaccines.

There are no shortcuts in science. We all know how unreasonably impatient and demanding we Americans have become. The question now is how much our leaders will indulge unreasonable demands and lack of patience and discipline, to the undeserved enrichment of private corporations, the detriment of credulous patients, and the ultimate degradation of proper scientific research. Accelerated approval of Aduhelm is a step in the wrong direction and mark of shame for the still-young Biden regime.

Permalink to this post