Marc Archambault smiled broadly Wednesday as he walked to the microphones at Butler Hospital in Providence, R.I. The silver-haired real estate agent was about to become the first person outside of a clinical trial to be treated with a new Alzheimer's drug in almost two decades.
"Obviously, I am very happy to have this," said Archambault, 70, who is in an early stage of the disease. "It's amazing."
The celebratory air at the news conference masked a growing furor over the Food and Drug Administration's highly contentious approval of the drug, called Aduhelm, last week. The monthly intravenous treatment is designed to slow cognitive decline, but whether that is the case remains so unclear that the FDA approved the medication on a different basis — its ability to reduce amyloid beta plaque in the brain.
For days, critics have blasted the approval in opinion columns and tweets, saying there is insufficient evidence of efficacy and expressing skepticism about whether getting rid of amyloid clumps improves brain function. They argue the drug — with a list price of $56,000 a year per patient — offers false hope while threatening Medicare's financial health and patients' pocketbooks. Three members of an FDA advisory board that recommended against approval of the drug have quit.
Public Citizen, a watchdog group that frequently criticizes the FDA, on Wednesday called for three top FDA officials to resign, saying the approval was "reckless."
But supporters have expressed confidence the drug will help patients such as Archambault stay in the earliest stages of the disease longer and lead to more treatments that might be more effective.
Much of the debate centers on the FDA's surprise decision to approve a broad label for the treatment, which theoretically means any of the more than 6 million people with Alzheimer's could receive it. As a practical matter, doctors and insurers will be left to decide whether to restrict the drug to the population studied in the clinical trials — people with mild cognitive impairment and early dementia, both caused by Alzheimer's. That's a job many physicians and insurers are unhappy to be stuck with, saying more FDA guidance is needed.
"Instead of a limited pool of eligible patients, you now have every patient and every family with Alzheimer's thinking maybe they should try this," said Steve Miller, chief clinical officer for the insurance company Cigna. "The FDA has transferred its responsibility down to the payers, and making payers out to be the bad guy."
Cigna and many academic medical centers have signaled they are likely to limit the drug to early-stage patients.
Other critics have complained about the FDA's use of "accelerated approval," which relies on a "surrogate endpoint" that is thought likely to predict clinical benefit but is not a measure of benefit itself. In this case, that surrogate is reduction in amyloid, a sticky compound that many scientists believe damages communication between brain cells and eventually kills them.
Acting FDA commissioner Janet Woodcock, in an interview with the trade publication BioCentury published Tuesday, said she wasn't involved in the decision but defended it as clearly meeting the agency's standards for accelerated approval.
The data on amyloid clearing "were quite solid," she said. There were "multiple trials showing a significant reduction in amyloid plaque in the brain." The FDA will require a confirmatory trial for Aduhelm, the brand name of the generic aducanumab, and could restrict its use or remove it from the market if it is shown to not be effective.
The FDA declined a request for Woodcock to elaborate on her remarks.
Patrizia Cavazzoni, director of the FDA's drug center, noted to reporters last week that accelerated approval has led to a "dramatic leap forward in the cancer space in the last 20 years, and we believe it serves as a model that we hope can be replicated with neurodegenerative diseases." Many advocates welcome that approach.
But some critics have faulted the oncology process, saying it allows costly drugs onto the market that don't necessarily prolong survival. And they say getting an ineffective drug off the market is difficult.
In Congress, some Democrats are complaining about the price of the new Alzheimer's drug, made by the Massachusetts-based biotech giant Biogen, and threatening congressional hearings. In an interview, Rep. Peter Welch, D-Vt., called the price "cruel," noting that beneficiaries in the traditional Medicare program would face cost-sharing of more than $11,000 a year if they did not have supplemental insurance coverage. And Part B premiums could go up for everyone.
Biogen said it was unable to provide someone for an on-the-record interview. Last week, Biogen chief executive Michel Vounatsos told CNBC the $56,000 price was "fair" and pledged not to increase it for the next four years.
Meanwhile, questions swirl about how the insurer that will undoubtedly be faced with the biggest check for the drug — Medicare — will cover the medication and related services.
The Centers for Medicare and Medicaid Services, which oversees the two government health plans, was surprised by the broad label, according to two former government officials who spoke on the condition of anonymity to describe internal discussions at the agency.
"They are really scrambling right now to figure out what to do," said one of the individuals.
CMS Administrator Chiquita Brooks-LaSure declined to tell reporters recently how the agency will handle the drug. Some health experts are calling for Medicare to develop a national coverage determination — a process that could take months or longer — that would limit coverage to early-stage patients. Such a decision also could avoid a patchwork of policies from local Medicare contractors.
Another complication is that the PET scans used to detect amyloid clumps — critical to diagnosing Alzheimer's — can cost thousands of dollars and are not covered by Medicare. Nor are the multiple follow-up scans needed to check for tiny brain bleeds sometimes caused by the drug.
"My greatest concern is around people with families with Alzheimer's disease," said Joshua D. Grill, an Alzheimer's researcher at the University of California at Irvine. "Few can afford the financial burden in the first place, let alone the additional costs of Aduhelm."
He said the cost of an amyloid PET scan was at least $5,000. "Doctors, families, even we researchers need more guidance," Grill said. Spinal taps offer a more affordable way of determining amyloid levels, but some patients shy away from them.
Because the drug is administered in doctors' offices and other outpatient settings, it will be included under Medicare Part B, which covers expensive intravenous drugs for cancer and other diseases. The Kaiser Family Foundation recently estimated that if 1 million Medicare beneficiaries receive Aduhelm, the total spent in a single year would be $57 billion. Medicare spent $37 billion on all Part B drugs in 2019.
Despite the unanswered questions, doctors are scrambling to figure out how to give the drug and to whom. They say patients have been phoning, texting and emailing constantly since the FDA approval was announced June 7.
Richard B. Lipton, a neurologist at Albert Einstein College of Medicine whose mother died of Alzheimer's, supports the FDA approval.
"The question I asked myself is, 'If this were available while my mother was still alive, would I have given her the drug?' And the answer was, unequivocally yes," he said. "And that is some mix of knowledge and emotion, and I'm not saying that it is a fully objective decision."
Phil Gutis wears an identification bracelet in case he gets lost from his home in New Hope, Pa. (Rachel Wisniewski/For The Washington Post)
