Alzheimer’s drug wins FDA approval after studies show it slows the disease

Questions remain about the treatment, Leqembi, sold by Biogen and Eisai, including its safety and whether Medicare will cover it.

Biogen is based in Kendall Square, Cambridge.Adam Glanzman/Bloomberg

Federal regulators on Friday approved a new drug for Alzheimer’s disease that moderately slowed cognitive decline in a closely watched study, raising hopes for patients and their families that it will become a useful weapon in the fight against an insidious condition that afflicts millions of Americans.

The treatment, made by Cambridge biotech Biogen and Japanese drug maker Eisai, decreased cognitive decline by 27 percent over an 18-month trial involving nearly 1,800 people in the early stages of Alzheimer’s. It also significantly lowered levels of a protein called amyloid that forms plaque in the brains of some people with the disease.

Although it doesn’t stop or reverse the devastating form of dementia, scientists and patients and their families welcomed the positive news — a rarity after decades of failed attempts to treat the disease by clearing amyloid plaques. Yet many questions remain about its safety, how meaningful its modest effect will be to patients, and whether insurers will cover the medicine.

The drug, called lecanemab during clinical trials, will be marketed as Leqembi and administered through an hourlong infusion every two weeks. Eisai said the drug would cost $26,500 per year, but estimated its value to society at $37,500. That price tag is still higher than the $8,500 to $20,600 range deemed cost-effective by the Institute for Clinical and Economic Review, an influential Boston-based drug-pricing watchdog.

For Biogen in particular, the Food and Drug Administration approval provides a chance for redemption after its disastrous rollout of another Alzheimer’s therapy, Aduhelm. That drug was approved in June 2021 despite doubts about its safety and effectiveness.

Many hospitals decided they wouldn’t offer Aduhelm, originally priced at $56,000 a year, and Medicare regulators and private insurers refused to pay for it, except in clinical trials. A scathing report released by two congressional committees last week criticized the FDA for “inappropriate” coordination with Biogen and faulted the drugmaker for its “aggressive” plans to maximize profits.

Although Eisai took the reins on working with regulators on Leqembi, a successful commercial launch could help Biogen repair its tarnished reputation — and refill its coffers. The companies will split profits of the drug, which some analysts predict could eventually generate sales of $8 billion a year.

“Patients at an early stage of the disease and their caregivers can now consider a new treatment option with their doctors,” said Biogen president and chief executive Christopher A. Viehbacher, whom the company’s board appointed to succeed Michel Vounatsos following the Aduhelm debacle. “Our focus now is on the path forward, working alongside Eisai with the goal of making Leqembi available to patients who may benefit from this treatment as soon as possible.”

Hugh Courtney, who suffers from mild cognitive impairment, got an infusion of Biogen's Alzheimer's drug, then called lecanemab, during clinical trials, at McLean Hospital in Belmont last June.Lane Turner/Globe Staff

Unlike Aduhelm, which provided modest benefits in one trial and failed in another, Leqembi’s clinical trial results were unequivocal. “There’s really no controversy about whether there was a difference between lecanemab and a placebo,” said Brian Skorney, a biotech analyst at the investment bank Baird.

But numerous bottlenecks could limit distribution of the new drug, which might not initially be covered by insurers. It was given accelerated approval by the FDA, based on earlier clinical data suggesting that removing amyloid can slow the disease. A previous Medicare ruling on Aduhelm and similar amyloid-busting drugs will restrict coverage of Leqembi until the FDA conducts a more thorough review of the recently completed 1,800-person study required for a full approval. That might not come until late this year.

In a recent interview with the Globe, Ivan Cheung, chairman and chief executive of Eisai’s US operations, said that access to the drug could potentially be “limited” before the full approval. “There’s a lot of work to get the health system ready,” he said.

Identifying patients eligible for the drug is one challenge, Cheung said. Although more than 6 million Americans have Alzheimer’s, Leqembi is approved only for people who show evidence of amyloid buildup in their brains and are diagnosed with mild cognitive impairment or mild dementia.

Biogen and Eisai previously estimated that 1 million to 2 million people may fit those criteria. Neurologists will need to conduct cognitive assessments and perform brain scans or spinal taps to look for amyloid to identify eligible patients — time-consuming and pricey diagnoses that have not routinely been made because, until now, there were no medicines to slow the disease. And hospitals will need to find space and staff to administer infusions.

“I don’t think the health care system is prepared for all of this,” said Dr. Alvaro Pascual-Leone, a cognitive neurologist and the medical director of the Wolk Center for Memory Health at Hebrew SeniorLife in Boston. “There is going to be a lot of demand, a lot of hope, a lot of expectations about this treatment that needs to be managed. Otherwise, there’s going to be a lot of frustration for patients and families.”

Experts also say that recipients will need to be carefully monitored for signs of brain bleeding and swelling that occurred in some patients who received Leqembi in clinical trials. Those reactions likely contributed to the deaths of three people who were also on blood thinners, according to media reports from Science and STAT, although Eisai dismissed the connection to its drug.

Monitoring would include periodic brain scans and neurological examinations, said Dr. Thomas Wisniewski, director of the Alzheimer’s Disease Research Center at NYU Langone Health. “That would be very difficult for most primary care physicians,” he said.

It’s unclear when hospitals will start providing the drug to patients. A spokesperson for Mass General Brigham, the state’s largest health care provider, said medication experts who make up the system’s Pharmacy and Therapeutics Committee need to review Leqembi before deciding whether to offer the drug.

In September 2021, the same committee decided not to offer Aduhelm to patients amid concerns about its safety and effectiveness. Neurologists at other hospitals said that they expect to offer Leqembi to eligible patients, although no formal decision has been made.

The US Food and Drug Administration building in Silver Spring, Maryland. Jacquelyn Martin/Associated Press

“It’s a fairly lengthy review process,” Wisniewski said. “There may be a bit more scrutiny because Alzheimer’s drugs have such a bad reputation, high failure rate, and a lot of side effects.”

Even when hospitals start offering the drug, the vast majority of potential patients may not be able to afford it until public or private insurers cover the cost. Doubts about Aduhelm led the Centers for Medicare and Medicaid Services to restrict coverage of all amyloid-targeting antibody drugs greenlit by an accelerated approval. That ruling was a death knell for Aduhelm, but the agency’s administrator has suggested that the door is open to potentially reconsider that ruling for new drugs.

Skorney, the Baird analyst, expects CMS will decide whether to cover the drug — a decision that typically influences commercial insurers — before the end of the year.

The drug’s benefit boiled down to a 0.45-point change on an 18-point scale, but doctors disagree on how noticeable of a difference that will translate to in the day-to-day lives of patients.

“It might be statistically significant, but how clinically meaningful is that going to be?” said Dr. Brian Silver, vice chair of clinical operations in neurology at UMass Memorial Medical Center. “The magnitude of the impact is probably not going to be as great as we would like.”

Dr. Stephen Salloway, who oversees neurology and the Memory and Aging Program at Butler Hospital in Providence, R.I., and ran one of the Leqembi trial sites, believes the benefit is meaningful. “Everyone is declining overall, but some are declining less than others,” he said.

Some scientists hope that giving the drug to patients before they develop signs of cognitive decline could lead to more dramatic effects, and maybe even prevent the disease. Biogen and Eisai are testing that hypothesis in a clinical study. Eisai is also testing Leqembi in combination with its experimental drug that removes a protein called tau that damages brain cells in those with Alzheimer’s.

“We have a long way to go to one day stop the progression of this disease or prevent this disease altogether. But it has to start somewhere,” Eisai’s Cheung said. “We hope this is the beginning of a paradigm shift, which ultimately will require potentially multiple therapies, multiple mechanisms.”