Aduhelm, Biogen’s new Alzheimer’s drug, won FDA approval. Now doctors, patients, and insurers face tough decisions about care and cost.

Normally, the approval of the first new drug for patients with Alzheimer’s disease in almost 20 years would be cause for celebration, and, in some cases last week, it was.

But the FDA’s decision to approve aducanumab on June 7 also met with an unusual chorus of criticism from Alzheimer’s experts, who said evidence that the high-priced drug actually improves thinking ability — the end point that really matters to patients and families — was lacking. Instead, the FDA relied primarily on the fact that the drug, which will be branded Aduhelm, reduced clumps of amyloid in the brain. These deposits are a key indicator of Alzheimer’s, but proof that reducing them improves brain functioning is slim. The agency concluded that Aduhelm’s trials showed that reducing amyloid is “reasonably likely to predict a clinical benefit.”

The FDA insisted that the drug’s maker, Biogen, begin a new clinical trial to further test whether aducanumab works, a step many critics argue should have been taken before approval. Two previous clinical trials were stopped early and had mixed results. One was promising for cognitive function. An FDA advisory panel recommended against approval of the drug, and three members quit after that advice went unheeded.

Amid all the controversy and uncertainty around aducanumab, it is clear that the drug is raising major issues of medical practice, health-care costs, and the future of drug regulation. Philadelphia area dementia specialists, whose patients have begun asking about the drug, are preparing for complex discussions about Aduhelm’s significant side effects, its potential benefits, and insurance coverage.

» READ MORE: Patient Perspective: FDA’s approval of Biogen’s Alzheimer’s drug gives patients, families hope

Meanwhile, the Alzheimer’s Association, which has hailed Aduhelm as a rare glimmer of hope for people with a progressive, fatal disease, this week pronounced Biogen’s proposed price — a whopping $56,000 a year — “simply unacceptable” and said it would be an “insurmountable barrier” to access. It called for a price cut. Joanne Pike, the organization’s chief strategy officer, would not name a specific, lower price. (The Institute for Clinical and Economic Review last month said the “insufficient evidence” for Aduhelm supports a value-based price of $2,500 to $8,300 or as high as $23,100 in the most optimistic analysis.)

Pike supports the FDA approval. “We believe it was the right decision and a milestone,” she said.

Biogen has said it will begin shipping Aduhelm to hundreds of sites in about a week, but then what? Doctors said few of their dementia patients could afford to pay cash for the drug and associated testing. Insurance coverage is uncertain. Medicare’s approval is especially important because most Alzheimer’s patients are 65 and older.

“If Medicare does not cover it, it will be a drug that will simply not be used,” said David Weisman, a neurologist at Abington Neurological Associates who treats patients with dementia and runs clinical trials of new treatments.

Biogen declined to comment on availability of its drug or insurance coverage. A spokesperson for the Centers for Medicare and Medicaid Services (CMS), which administers the Medicare program, said only that CMS “would have more information soon.” Independence Blue Cross said it is waiting to see what CMS does.

Oh, and the FDA approval document says all patients with Alzheimer’s are eligible for the drug, which was only tested in people at early stages, another decision that baffled dementia experts. Will insurers and doctors go along with that?

Weisman has written a five-page letter he hopes will help patients understand the new dilemma. He starts the letter by recapping a 2007 trial of a monoclonal antibody that reduced amyloid deposits in the brain but had no clinical benefit. He ends it conflicted about how to balance the unknown benefit of the new drug with suffering from Alzheimer’s and a significant side effect of treatment: brain swelling in 35% of patients.

“This uncertainty feels terrible,” he wrote, ”but better than embracing dogma.”

In an interview, Weisman said he is “in the middle of the road” on the new drug. He thinks one trial’s positive clinical results are encouraging, but still considers aducanumab “experimental.” He’s open to prescribing it, especially for people who can’t qualify for trials of other drugs, but also will encourage patients to join other trials. His practice is currently participating in tests of three other drugs that are, like aducanumab, monoclonal antibodies that target amyloid.

Weisman thinks Aduhelm is most appropriate for patients who would have qualified for the clinical trials. The FDA decision to approve it for all Alzheimer’s patients, he said, is “dangerous” and an “abandonment of responsibility.”

Jason Karlawish, co-director of the Penn Memory Center, is a widely quoted critic of the drug approval, even though his center participated in two Aduhelm trials. Before the drug was approved, he said he wouldn’t want to prescribe it. After the FDA decision, though, he said he thought he had to offer it to patients who understood the risks and want to try the drug. “I remain an unenthusiastic prescriber,” he said. But, he added, “I have to respect that one of my chief goals is to help people maintain their autonomy.”

Carol Lippa, director of the Cognitive Disorders and Comprehensive Alzheimer’s Disease Center at Jefferson Health, thinks some of her fellow dementia experts have been overly harsh. Six million Americans have Alzheimer’s, and no drug can slow their decline. She is persuaded that Aduhelm might. “We know where you’re going to be in a few years if you don’t take this,” she said.

Regardless of demand, patients can’t just get a new drug immediately unless they’re so wealthy they don’t care about the price tag. The decision on whether Medicare will cover the drug, and under what conditions, could be months away.

“It’s not something where you can say, ‘Come on in. We’ll give it to you tomorrow,’ ” Lippa said. “I’m sort of waiting for further instruction.”

One big issue is that Alzheimer’s diagnoses are 60% to 90% accurate, depending on which doctors are involved, Weisman said. There are many kinds of dementia. Some have similar symptoms but different types of brain pathology. Most dementia patients are never tested for amyloid buildup. Specialists like Karlawish, Lippa, and Weisman tend to make the most accurate diagnoses based on symptoms. Outside of clinical trials, that hasn’t mattered much because of the lack of treatments.

It seems obvious, though, that a very pricey drug that attacks amyloid clumps should be given only to patients known to have such clumps. Currently, the primary way to find that out in living patients is through special, expensive PET scans. Medicare has so far declined to cover these, arguing that they’re pointless because they don’t change treatment. Aduhelm will force Medicare to reconsider that stance.

Insurers have been more open to paying for tests of spinal fluid, which is taken through spinal taps, but Karlawish says they’re harder to interpret.

“The biomarker door will have to be opened for aducanumab to be used,” said Weisman, referring to the amyloid tests.

The drug protocol will also require one MRI before treatment and two during the first year of monthly infusions.

Weisman said the choices will be difficult for everyone. “I think this is not an impulsive decision,” he said. “I think it really has to be a contemplative decision taking the patient’s risk tolerance and goals into account.”