The Food and Drug Administration on Thursday fully approved the Alzheimer’s treatment Leqembi, a pivotal decision that will expand access to the expensive drug for older Americans.
Medicare announced shortly after the FDA approval that it is now covering the antibody treatment for patients enrolled in the insurance program for seniors, though several conditions apply.
Leqembi is the first Alzheimer’s antibody treatment to receive full FDA approval. It is also the first such drug to receive broad coverage through Medicare.
Leqembi is not a cure. The treatment slowed cognitive decline from early Alzheimer’s disease by 27% over 18 months during Eisai’s clinical trial. The antibody, administered twice monthly through intravenous infusion, targets a protein called amyloid that is associated with Alzheimer’s disease.
Medicare coverage is a crucial step to help older Americans with early Alzheimer’s disease pay for the treatment. With a median income of about $30,000, most people on Medicare cannot afford the $26,500 annual price of Leqembi set by Eisai without insurance coverage.
Medicare had previously only agreed to cover Leqembi for patients participating in clinical trials after the treatment received expedited approval in January. This policy had severely restricted access to the drug.
To be eligible for coverage, patients must be enrolled in Medicare, diagnosed with mild cognitive impairment or mild Alzheimer’s disease, and have a doctor who is participating in a data-collection system the federal government has established to monitor the treatment’s benefits and risks.
Joanna Pike, president of the Alzheimer’s Association, the lobby group that advocates on behalf of people living with the disease, said although Leqembi is not a cure, it will help patients in the early stages of the disease maintain their independence, conduct their daily lives, and spend more time with their families.
“This gives people more months of recognizing their spouse, children and grandchildren,” Pike said in a statement Thursday. “This also means more time for a person to drive safely, accurately and promptly take care of family finances, and participate fully in hobbies and interests.”
But the treatment carries serious risks of brain swelling and bleeding. Three patients who participated in Eisai’s study died. FDA scientists have said it is unclear if Leqembi played a role in these deaths.
Alzheimer’s disease is the most common cause of dementia among older adults and the sixth leading cause of death in the U.S., according to the FDA.
Dr. David Knopman, a neurologist who specializes in Alzheimer’s disease at the Mayo Clinic in Minnesota, said Leqembi clearly demonstrated a benefit to patients in Eisai’s trial, though he cautioned the efficacy of the treatment was modest.
Knopman said appropriately diagnosed and informed patients should be able to decide for themselves whether they want to take Leqembi after weighing the benefits and risks of the treatment as well as the potential logistical challenges of finding a place to receive the twice-monthly infusions.
To receive coverage, Medicare is requiring patients to find a health-care provider participating in a registry system that collects real-world data on the drug’s benefits and risks. The system is controversial. The Alzheimer’s Association and some members of Congress are worried this requirement will create barriers to treatment.
There are concerns that the number of health-care providers participating in such registries will be limited, and that people in rural towns and other underserved communities will have to travel long hours to find such a provider.
The Centers for Medicare and Medicaid Services has set up a nationwide portal to make it easy for health-care providers to submit the required data on patients receiving Leqembi. The free-to-use portal went live moments after the FDA decision on Thursday.
Rep. Anna Eshoo of California, the ranking Democrat on the House Subcommittee on Health, and Rep. Nanette Barragan, D-Calif., raised concerns in a letter to CMS last month that patients could struggle to find a doctor participating in the system.
Alzheimer’s is typically diagnosed with the help of a PET scan to detect the amyloid protein associated with the disease or in some cases with a spinal tap. Medicare currently only covers one PET scan per lifetime for dementia. It is unclear if the program plans to change that policy.
There’s also concern that there could be too few specialist physicians and locations to administer the infusions if Leqembi is broadly embraced as a treatment and patient demand for the antibody is high.
Some studies have estimated that wait times for antibody treatments like Leqembi could range from months to even years over the next decade depending on demand.
Tomas Philipson, who advised the FDA commissioner and CMS administrator during the second Bush administration, said the registry is an unnecessary hurdle and Medicare should drop it, but he doesn’t believe the requirement will create an insurmountable barrier to patients accessing Leqembi.
If demand for Leqembi is high, doctors will have an incentive to participate in the registry and the drug companies will want to help, said Philipson, an expert on health-care economics at the University of Chicago.
How high demand will be for Leqembi is uncertain, he said. Families worried about the serious side effects may opt not to take the treatment, while others will decide the benefits outweigh those risks, he said.
Leqembi’s price tag and the treatment’s benefit-risk profile are controversial.
Medicare patients treated with Leqembi will pay 20% of the medical bill after they meet their Part B deductible, according to CMS. Costs may vary depending on whether the patient has supplemental Medicare coverage or other secondary insurance, according to the agency.
Patients could face up to $6,600 in annual out-of-pocket costs for Leqembi even with Medicare coverage, according to a study published in the journal JAMA Internal Medicine. The treatment could cost Medicare up to $5 billion a year depending on how many people receive the infusions, the study estimated.
Sen. Bernie Sanders, I-Vt., chair of the Senate Health Committee, has called Leqembi’s price “unconscionable” and in a letter last month asked Health and Human Services Secretary Xavier Becerra to take action to reduce the cost.
Sanders said patient out-of-pocket costs for Leqembi would amount to a sixth of many seniors’ total annual income and noted the high cost of the treatment could increase premiums for everyone on Medicare.
Eisai says its $26,500 annual list price for Leqembi is lower than the company’s estimate of $37,600 for the total value of the treatment for each patient. The Institute for Clinical and Economic Review, a nonprofit that analyzes health-care costs, estimated in April it should be priced at $8,900 to $21,500 per year.
Though Leqembi could prove costly to Medicare, Philipson said delaying coverage of the treatment would result in significant increased health-care spending as people with mild Alzheimer’s disease, which can be managed at home, progress to more serious disease that requires expensive nursing home care.
Philipson and his colleagues at the University of Chicago estimated that delaying Medicare coverage of Alzheimer’s antibody treatments by one year would result in $6.8 billion in increased spending. By 2040, health-care spending would rise by $248 billion.
Thursday’s full FDA approval comes after a panel of six outside advisors voted unanimously in June in support of the drug’s clinical benefit to patients. The panel was unusually small because some members recused themselves due to conflicts of interest.
The American Academy of Neurology stated in a February letter to CMS that there is a consensus among its experts that Eisai’s clinical trial of Leqembi was well designed and the results were “clinically and statistically significant.”
Some nonprofit groups such as Public Citizen, a consumer advocacy organization, strongly opposed FDA approval of Leqembi. A representative from Public Citizen told the advisory panel that the evidence for the drug’s benefit does not outweigh significant risks of brain swelling and bleeding.
And representatives from the National Center for Health Research and Doctors for America, also nonprofits, told the panel that Eisai’s clinical trial did not include enough Black patients, who are at higher risk for Alzheimer’s disease.
Leqembi has technically been approved for the U.S. market since January, when the FDA cleared the treatment under an accelerated pathway. The FDA uses expedited approvals to save time and get drugs to patients suffering from serious diseases more quickly.
But Medicare refused to cover the Leqembi at that time, asking for more evidence that the expensive treatment had a real clinical benefit for patients that outweighed the risks.
The program’s cautious coverage policy stems from the FDA’s controversial 2021 approval of another Alzheimer’s antibody treatment called Aduhelm, also made by Eisai and Biogen.
The FDA’s advisory committee declined to endorse Aduhelm because the data did not support a clinical benefit to patients. Three advisors resigned after the agency’s decision to approve the treatment anyway.
Knopman is one of the advisors who resigned over the FDA’s decision on Aduhelm. He said the data for Leqembi is different. Eisai conducted a clean trial that showed the antibody had a modest clinical benefit for patients, Knopman said.
An investigation by Congress subsequently found that the FDA’s approval of Aduhelm was “rife with irregularities.”
Sanders, in his letter to Becerra, said the FDA “has a special responsibility to restore the public trust after its inappropriate relationship with Biogen during the agency’s review of a prior Alzheimer’s drug, Aduhelm.”