FDA narrows recommended use of Biogen Alzheimer’s therapy after flood of criticism

Marc Archambault, a 70-year-old resident of South Kingstown, R.I., received an infusion of Aduhelm, Biogen's approved drug for Alzheimer's disease.Jessica Rinaldi/Globe Staff

The US Food and Drug Administration, which approved Biogen’s controversial new drug for Alzheimer’s disease despite scant evidence that it works, narrowed its recommended use of the medicine on Thursday to patients with early symptoms, citing “confusion regarding the intended population for treatment.”

Biogen had already said Aduhelm was meant for Alzheimer’s patients with mild cognitive impairment, the group studied by the Cambridge drug maker in three clinical trials. But the FDA didn’t limit the medication to those people, who number 1 to 2 million in the United States, when it approved Aduhelm on June 7, raising the specter that anyone diagnosed with the disease — an estimated 6 million Americans — might seek it.

A recent analysis by the news site STAT found that if all 5.8 million Medicare-eligible adults with Alzheimer’s took the drug — with a price tag of $56,000 a year for the average patient — it would cost the government $334.5 billion, or nearly half the budget of the entire Department of Defense.

The FDA, which has been trying to justify Aduhelm’s approval even though its own expert advisory panel recommended against it, conceded Thursday that its original usage language was confusing to some doctors and patients.

“Hearing those concerns,” the FDA said in an e-mail to the Globe, the agency “believes that it was important to clarify the intent” of the label approved for Aduhelm. The FDA said “it is appropriate to initiate treatment in patients with the mild cognitive impairment or mild dementia stages” because “this is the population who were entered into the clinical trials.”

Nonetheless, the agency still appeared to leave wiggle room for doctors to prescribe Aduhelm to a broader group of Alzheimer’s patients.

“Some patients may benefit from ongoing treatment even if they progress from mild cognitive impairment or mild dementia to later stages of the disease during treatment,” the FDA said. As a result, the drug “label,” a 23-page guide for use of the medication, still says Aduhelm is “indicated for the treatment of Alzheimer’s disease” and doesn’t flatly say people with later symptoms should not take it. That’s appropriate, the FDA said in its e-mail, “because the disease is progressive.”

Dr. Peter Bach, director of the Center for Health Policy and Outcomes at Memorial Sloan Kettering Cancer Center in New York and a critic of high drug prices, said the FDA mistakenly bowed to pressure from advocates for Alzheimer’s patients by approving a drug he considers ineffective and potentially harmful.

Now, he said, the FDA is trying to repair its image and show it has listened to critics, including insurers who have complained about Aduhelm’s cost and the muddled results from clinical trials. But the agency has failed to fix the problem because, he said, Biogen never provided compelling scientific evidence that the medication works.

“The whole thing stinks from a scientific perspective,” Bach said. “Now they can say, ‘We heard, we heard, we’ve taken serious action, we’ve curtailed the use of this drug.’ It gives them talking points without addressing the heart of the matter, which is that the drug shouldn’t have been marketed.”

Some doctors who treat Alzheimer’s patients had already been preparing to prescribe the drug to patients with mild symptoms even though several say the scientific evidence supporting its approval was inconclusive.

Dr. Teresa Gomez-Isla and Dr. Kirk Daffner, Alzheimer’s specialists at Massachusetts General Hospital and Brigham and Women’s Hospital, respectively, said Thursday that their hospitals could start prescribing Aduhelm in the next few months to patients who might benefit. But, they said, they considered the FDA approval “premature” and would have preferred that Biogen conduct another late-stage clinical trial.

One doctor who has championed the drug applauded the FDA decision to narrow its use.

Dr. Stephen Salloway, who oversees neurology and the Memory and Aging Program at Butler Hospital in Providence, one of the clinical trial sites, said Alzheimer’s experts have consistently recommended that Aduhelm be limited to patients with mild cognitive impairment.

“Today’s announcement is a welcome revision to the label,” said Salloway, a paid consultant for Biogen. He contends the drug did slow cognitive decline in some patients with early symptoms. Salloway said that he treated 17 patients with Aduhelm ― called aducanumab during the trials ― and that 10 didn’t deteriorate while on it.

Alfred Sandrock Jr., Biogen’s head of research and development, said in a company statement Thursday that the firm supported a “label update” after discussions with prescribing physicians, drug regulators, and patient advocates. Biogen said it wanted to make explicit that “there are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied.”

One of the most closely watched experimental drugs in recent history, the medicine from Biogen and its Japanese partner Eisai is a monoclonal antibody made from the immune cells of older people with no or uncommonly slow cognitive decline. It is administered in monthly intravenous infusions.

Aduhelm generated contradictory results in two late-stage clinical trials. In one study, Biogen said, a high dose could delay cognitive decline by 22 percent, or about four months over 18 months, an encouraging result. The other trial failed to prove the drug was effective.

Critics have also noted that the drug caused side effects in some patients, including brain swelling, although that didn’t usually result in serious symptoms.

Based on the conflicting trial results and potential side effects, an FDA scientific advisory committee in November voted 10-0, with one panelist voting “uncertain,” that the agency shouldn’t approve the drug. But the FDA cleared it anyway to the surprise of some experts, prompting three members of the committee to quit in protest.

On Thursday one of the doctors who quit the panel, Dr. Aaron Kesselheim, a Harvard Medical School professor, said it’s better to have more precise information on the drug label than not, “but this doesn’t change anything about the problematic approval of the drug itself.” He had previously called Aduhelm’s approval “perhaps the worst” drug authorization in its recent history.

Biogen is facing a fierce backlash and congressional inquiries over the approval and pricing of the drug, which is expected to be a multibillion-dollar blockbuster.

A top official with the Alzheimer’s Association, which enlisted celebrities such as Samuel L. Jackson in a public campaign to persuade the FDA to approve it, has called the price “unacceptable.” The Democratic chairs of two key House committees recently announced an investigation of the medication and how the FDA approved it.

And an influential Boston drug-pricing watchdog group last week stood behind its withering assessment of the drug, saying it deserved an annual price tag between $3,000 and $8,400, roughly a tenth of what Biogen plans to charge. The watchdog group, formally called the Institute for Clinical and Economic Review, or ICER, cited the drug’s modest benefits and potential side effects.

However, Biogen has defended the cost of the monoclonal antibody, saying that other novel medicines using similar technology are much more expensive.

Biogen spokeswoman Allison Parks noted that immunotherapies like Merck’s blockbuster Keytruda — which treats more than a dozen forms of cancer — cost upward of $150,000 a year, and anti-inflammatory medicines such as AbbVie’s best-selling Humira cost more than $70,000 a year.

Aduhelm is the first new drug for Alzheimer’s approved since 2003. The FDA cleared it under a less common “accelerated approval pathway” reserved for medicines that fill a serious unmet need.

The FDA typically uses this approach when regulators are uncertain about the clinical benefits of a drug and rely on another yardstick that suggests it would help patients. In this case, that was Aduhelm’s reduction of a sticky substance called amyloid that clumps into plaques in the brains of people with Alzheimer’s. That reduction, Biogen says, is “reasonably likely to predict” that the drug will benefit such patients. Other experts say that hasn’t been proven.