The federal Food and Drug Administration has created an instant medical and regulatory morass by giving an accelerated approval to Biogen’s costly prescription medication targeted at patients with Alzheimer’s disease.

This is the first drug to win the precious official nod from the FDA in almost two decades.

But the agency’s OK to market aducanumab (pronounced “add-yoo-CAN-yoo-mab”), which will go by the brand name Aduhelm, may go in the books as one of the sketchiest and most ferociously contested in recent times. The drug somehow overcame Everest-sized reasons why, at best, it needed further study — which it is supposed to get. And it faces Himalayan-sized criticisms that it will raise false hopes for those afflicted with a condition that is spiking in a fast-graying nation, and for which no effective medical remedy has been found.

It also may stick taxpayers with billions of dollars in hard-to-defend spending.

A rocky path to approval

Aduhelm, in the rosiest view, has shown some effect as a monoclonal antibody drug — a type of remedy that the public has learned much about both in cancer fighting as well as in the battle against the coronavirus pandemic. Biogen’s drug showed it could help in ridding the brain of “a protein, amyloid, that clumps into plaques in the brains of Alzheimer’s patients and is considered a biomarker of the disease,” the New York Times reported.

This, in turn, is supposed to slow the cognitive decline that, thus far, has proven to be a fearsome and irreversible aspect of Alzheimer’s. This is the medical theory under which researchers have toiled for years now. But this hypothesis, despite billions of dollars of spending, has not proved persuasive, and, indeed, is falling into disfavor and without a quick replacement.

Critics of the Biogen’s drug pointed to the manufacturer’s own two, large, and largely unsuccessful clinical trials, to underscore that ridding the brain of amyloids failed to show much progress in improving Alzheimer’s patients’ cognitive capacities or in delaying the disease’s progress. After the two trials, the drug maker announced it was abandoning the product into which it had sunk huge sums. But it then reexamined and reinterpreted data from its studies, arguing that its after-the-fact analyses showed its drug was useful and should be approved.

The FDA’s own independent experts, however, tore apart Biogen’s research and advised the agency — in stark and uncertain terms — to reject the drug. With that advice disregarded, members of the elite panel have started resigning in protest in increasing numbers.

As the Associated Press reported on a key and unconvincing measure of the drug’s effects:

“Patients taking aducanumab saw their thinking skills decline 22% more slowly than patients taking a placebo. But that meant a difference of just 0.39 on an 18-point score of cognitive and functional ability. And it’s unclear how such metrics translate into practical benefits, like greater independence or ability to recall important details.”

Despite independent experts’ assessments of that small gain and what might be a reasonable price for a medication that provided it, Biogen has said it plans to charge $56,000 annually for a typical regimen of the drug. The company pledged to keep that price for four years.

A drug that is neither cheap nor easy to use

But critics pointed out that the drug’s steep cost for uncertain benefit, if any, carries further challenges. The drug must be given as a monthly infusion, meaning it likely can only be administered in doctor’s offices, clinics, or hospitals — which will tack on additional costs.

Further, experts caution that doctors should not prescribe the drug too readily, say, if patients show simple forgetfulness or occasional confusion. Instead, clinicians have been advised to employ existing and less-than-optimal diagnostic tools to ensure patients may have early signs of dementia, including its most common form Alzheimer’s. In practical terms, this may mean that patients must undergo costly brain scans to detect brain plaques, believed linked to amyloid buildup.

They also likely would need to keep undergoing these pricey tests. That’s because Biogen’s drug “carries a warning about temporary brain swelling that can sometimes cause headaches, confusion, and dizziness. Other side effects included allergic reactions, diarrhea, and disorientation.”

With all the many other issues attached to aducanumab, the FDA further inflamed the opposition to the drug with yet another of its regulatory decisions: The medication was studied as a treatment only in early-stage Alzheimer’s patients. Its unsteady data came from those volunteers, not from individuals with more advanced disease.

But the FDA gave its accelerated approval for the drug’s widest use — with all Alzheimer’s patients. A huge rationale by the agency in greenlighting aducanumab was the desperation of patients and their families. The condition is nightmarish for them, what with its cognitive impairments, most notably memory loss, but also agitation, wandering, and loss of control over bodily functions. And as the Washington Post reported:

“About 6.2 million Americans have Alzheimer’s, a number projected to more than double by 2050, barring breakthroughs in treatment, according to the Alzheimer’s Association.”

Taxpayers may get stuck with billions of dollars in new costs

The FDA’s approval of this medication, though, cast a financial pall on the nation’s leading health care source for seniors: Medicare. As the news site Vox reported of what may be a new, $100 billion annual burden for the government health program:

“Now that aducanumab is approved by the FDA, the issue of coverage falls largely to Medicare, because of the age of the patient population most affected by Alzheimer’s, the federal program is likely to bear the brunt of the drug’s costs. In practice, if the FDA approves a drug, Medicare will pay for it. Aducanumab would be covered through Medicare Part B, which covers outpatient care, because it is an infusion treatment administered directly by doctors. To be covered by Part B, medical care must be ‘reasonable and necessary’ — a vague standard that has, for medications, historically been mostly synonymous with FDA approval. Because the drug is covered by Part B, doctors will even have a financial incentive to prescribe it. For prescription drugs, the program pays physicians the average price plus 6%, a policy that both Presidents Obama and Trump proposed changing but nevertheless remains in place … At the individual level, patients could face out-of-pocket costs anywhere from $0 for patients eligible for both Medicare and Medicaid, to $10,000 annually, since Medicare Part B can hold patients responsible for up to 20% of costs …”

The fiscal challenges posed by one drug should not loom so large, but, especially with the pandemic, federal health programs — especially Medicare and Medicaid — have been put under great pressure, with increasing concerns about the solvency of the programs. This is especially true because of the deep political divides in the country, with Republicans long opposed to any federal role in the U.S. health care system. The GOP, by the way, also has fought attempts to allow Medicare to use its huge clout to negotiate with Big Pharma over prescription drug costs.

In my practice, I see not only the harms that patients suffer while seeking medical services, but also the damage that can be inflicted on them by dangerous and bankrupting drugs. Yes, federal regulators have struggled to balance the immediate needs and concerns of patients and their loved ones with the rigorous and time-consuming testing of prescription medications. This became a significant problem during the worst of the HIV-AIDS crisis when the federal government and the FDA appeared to hamper important paths to treat a deadly illness.

What happens with speedier oversight

But has the agency over-corrected, particularly as it has been pressed by pro-business interests, arguing for less regulation and bureaucracy? Research has shown the FDA has speeded up drug approval processes — moves that have not necessarily resulted in more drugs getting to the market and improving and extending patients lives. Instead, the agency — which is depending more and more on fees generated from Big Pharma — has turned with greater frequency to less reliable measures of the safety and effectiveness of prescription drugs.

The FDA has increasingly accepted “surrogate endpoints” in evaluating products, approving them based, for example, on whether they shrink cancerous tumors or slow the advancement of diseases — not whether medications improve or prolong patients’ lives. Critics say the agency is flooding the market with drugs of dubious effectiveness (and safety), leaving the sick and injured with impossible decision making with their doctors, who may be equally baffled by an array of increasingly complex and costly treatments.

Biogen’s amyloid-scrubber is supposed to be tested further, with the FDA telling the drug maker it must conduct a sizable, rigorous clinical trial to show aducanumab’s real-world effectiveness. But it is unclear how long before the company must do this and produce results — potentially not for as long as a decade. Experts say it will be even more difficult to recruit participants in trials for this drug once it is on the market. Patients will ask themselves why they should risk foregoing it as a participant if it has any chance of work, right? Other drug makers, seeing the path that Biogen pursued, also soon may bang on regulators’ doors with other products targeting Alzheimer’s or other conditions because, why not? The FDA suddenly has made patient desperation and demand a part of the criteria in regulatory approval, critics say.

Medicare officials, doctors, and hospitals may put a brake on the agency’s hasty and ill-considered Biogen approval, discussing in detail with patients the many reasons why the drug may not be a reasonable option. Wouldn’t it have been better for the supposed taxpayer watchdog agency to have exercised more diligence? Or maybe the agency has gambled that its decision, by purpose or stroke of luck, opens a course to effective Alzheimer’s and dementia treatment? We need a lot more work from the FDA to show it is doing its job in advancing the public interest. This mess ought to be a resounding reason, by the way, for President Biden to look outside the agency for its next chief.