When will lecanemab be available? Eisai and Biogen Alzheimer's drug awaits FDA approval

Federal drug regulators will decide by July 6 whether to grant the first traditional approval to an amyloid-busting drug to treat Alzheimer's disease.

On June 9, the Food and Drug Administration's advisory panel of experts endorsed the drug, lecanemab, as effective – while not voting on the thornier question of how to advise doctors and patients about known side effects and medical risks. The FDA doesn't have to accept its advisory panel's recommendation when evaluating a drug but often does.

The decision will be closely watched by patient advocates and scientists alike because Eisai and Biogen's drug, sold under the brand name Leqembi, would be the first amyloid-targeting medication to pass the FDA's full review. It will also set expectations for patients who have been unable to afford the $26,500-a-year drug, which one study projected would cost taxpayers and families $2 billion to $5 billion a year. More than 6 million Americans live with Alzheimer's disease, the fifth-leading cause of death for adults over 65.

Doctors can already prescribe Leqembi. Why is FDA approval needed?

The FDA already has granted a type of conditional approval for Leqembi and Aduhelm, both of which are monoclonal antibodies that clear the protein amyloid from the brains of Alzheimer's patients. The FDA's "accelerated approval" is for drugs that serve an unmet medical need and achieve a goal, such as removing amyloid. But to get full approval, drugmakers must prove the drug works in a clinical study.

Doctors have prescribed Leqembi since January, when the FDA granted accelerated approval. But the Centers for Medicare and Medicaid Services refuses to pay for Leqembi, Aduhelm and other similar Alzheimer's drugs unless patients are enrolled in a clinical trial.

If the FDA grants traditional approval, Medicare will likely pay for the drug as long as prescribing doctors participate in a registry, or a database that tracks how well the drug works. Medicare said such registries are used to learn how patients fare after taking newly approved drugs or undergoing procedures. One example: tracking how well patients fare after getting heart valve replacement using a catheter.

The Alzheimer's Association said a registry is a "unnecessary and potentially harmful barrier."

“Medicare is supposed to be a rock-solid guarantee for Americans, and it is time for CMS to step up and provide Medicare access on the day of an FDA traditional approval," said Joanne Pike, Alzheimer’s Association president and CEO. "Americans living with Alzheimer’s disease deserve access to FDA-approved therapies without barriers, just like people with cancer, heart disease and HIV/AIDS.”

What did the clinical trials show?

An 18-month study showed people with early signs of memory and cognitive decline fared better on Leqembi compared with a placebo group that did not take the medication. Eisai said its study showed people on the drug declined 27% more slowly than a placebo group.

It was enough to win the unanimous endorsement this month from the FDA's Peripheral and Central Nervous System Drugs Advisory Committee, which found the study showed evidence of the clinical benefit.

Study participants who took the drug had lower levels of amyloid, a protein the accumulates in the brains of Alzheimer's patients. Some Alzheimer's researchers have long predicted removing or preventing clumps of amyloid from forming in the brain could delay or halt memory and thinking problems. But that view is not universal, and some researchers say too much time, effort and funding have targeted amyloid at the expense of competing ideas.

Dr. Lon Schneider, a professor of psychiatry and behavioral sciences at the University of Southern California Keck School of Medicine, said memory and thinking slipped both for people on the drug and placebo. It's just the group that took the drug worsened at a slower rate.

"It has modest effect," Schneider said. "It's really small."

Brain swelling, bleeding common

The FDA must decide whether such a modest benefit is worth safety risks, such as brain swelling and tiny bleeds common in this class of amyloid-clearing drugs. FDA staffers said the risk for such side effects appeared to be greater for patients who inherited two copies of the Alzheimer's risk gene ApoE4.

Dr. Merit Cudkowicz, an advisory panel member and chief of neurology at Massachusetts General Hospital, said ApoE4 testing should be "strongly recommended" so doctors and patients could be aware of potential harms.

"The risks were higher in this group," Cudkowicz said during the advisory panel meeting. "As a physician, I think you'd want to know the (ApoE4) status of your patient and have the chance to go over the risks and benefits in more detail."

Advisory panel members had mixed opinions about the safety of the drug for people on blood thinning medications. Though some advisory panel members recommended the drug be made available for patients on such anticoagulants, others were concerned that a small number of patients had serious side effects. Two patients on lecanemab died from brain bleeds, according to a FDA briefing document.

Cudkowicz said she would be wary of recommending Leqembi for patients on anticoagulants because of the limited data in the clinical trials. She said more data is needed to better understand potential risks such as major brain bleeding while on Leqembi and certain blood thinners.

Dr. Stephen Salloway, a professor of neurology and psychiatry at Brown University, said he expects the FDA will strengthen wording on the drug's label to inform doctors and patients about such risks.

FDA must decide on MRI coverage, genetic testing

If the drug is approved, Medicare must decide not only how it will cover the drug. The federal health program for adults 65 and older must decide whether to reimburse tests needed for those on the drug.

Patients must undergo tests such as a brain scan, spinal tap or blood test to show they have amyloid accumulating in the brain. Patients also must have multiple MRIs during the first year of treatment to check for side effects.

And because the clinical studies show people who who carry two copies of the ApoE4 gene have a higher likelihood of brain swelling and bleeds, some doctors want Medicare to pay for genetic testing.

Salloway said the testing should be covered to ensure patients can get equitable access to the treatment.

"All those things need to be covered," said Salloway, who directs a memory and aging program at Butler Hospital in Providence, Rhode Island. Testing "is a required part of this therapy. It's not optional."

'Doesn't make anyone better'

Doctors also worry families will want the drug even for loved ones whose memory and thinking problems have progressed so far that the drug is unlikely to help. The study tested people in an earlier stage of the disease called mild cognitive impairment or early dementia.

"They'll ask for it and we will have to say no," Schneider said. "There's going to be a certain amount of disappointment."

While patient groups have pressured the federal government to approve and pay for Leqembi, some doctors raised questions about the amyloid-busting drug's known harms and expense. Not only does Leqembi and other anti-amyloid drugs cause brain swelling and bleeds in some patients, it also will be costly for taxpayers and families, said Dr. Adriane Fugh-Berman, a Georgetown University professor of pharmacology and physiology and expert on pharmaceutical marketing.

"These drugs don't make anybody better," Fugh-Berman said. "This is wasting taxpayers' money to harm patients."

Ken Alltucker is on Twitter at @kalltucker, or can be emailed at alltuck@usatoday.com.

This article originally appeared on USA TODAY: FDA approval weighs benefits, harms of the Alzheimer's drug lecanemab