On Thursday, the Food and Drug Administration awarded a full approval to the Alzheimer’s disease treatment Leqembi, a decision expected to significantly increase use of the therapy and, potentially, others that work like it.
Developed by partners Eisai and Biogen, Leqembi received a conditional approval early this year. FDA staff concluded the drug was reasonably likely to provide some level of benefit to patients, based on results from a roughly 850-person study that showed sharp reductions of a protein many researchers believe to be the root cause of Alzheimer’s.
Insurers haven’t been convinced, however. Medicare, the government program covering the majority of U.S. patients with the disease, has in place a policy strictly limiting access to Alzheimer’s medicines that were given conditional approval and target that protein of interest, known as “amyloid beta.”
Medicare’s policy has curbed the use of both Leqembi and an earlier drug from Eisai and Biogen, Aduhelm, as it requires patients to be enrolled in a randomized clinical trial in order to get these therapies. The pushback has been so intense that Aduhelm, once pegged by Wall Street as a blockbuster product, generated only a few million dollars in its first full year on the market.
Eisai and Biogen have another shot at a multibillion-dollar Alzheimer’s drug with Leqembi, especially now that the FDA has granted full approval. The agency’s decision hinged on results from a larger, more recent clinical trial that found cognition and function declined 27% slower among participants who received Leqembi as opposed to a placebo.
“Today’s action is the first verification that a drug targeting the underlying disease process of Alzheimer’s disease has shown clinical benefit in this devastating disease,” said Teresa Buracchio, acting director of the FDA office that reviews neurological disease drugs, in a statement. “This confirmatory study verified that it is a safe and effective treatment for patients with Alzheimer’s disease.”
Medicare has said it will provide broader access to amyloid-targeting Alzheimer’s therapies that receive full approvals, though restrictions will remain. In particular, coverage would be contingent on patients and their doctors agreeing to participate in registries that collect data on how these treatments work in the real world.
While some Alzheimer’s groups and experts have criticized these proposed requirements as overly burdensome, Medicare last month emphasized any registry would be free and easy to use.
That would bode well for Leqembi’s uptake, according to Brian Skorney, an analyst at the investment firm Baird.
In a recent note to clients, Skorney wrote that the registry is a “minimal barrier for physicians who treat Alzheimer’s disease to prescribe Leqembi to their patients [and] reflects positively on the potential near-term success” of the drug.
Analysts at RBC Capital Markets have predicted Leqembi, which is currently priced at $26,500 per year, could at its peak reach $10 billion in annual sales. Eisai, meanwhile, has said it anticipates at least 10,000 patients in the U.S. will be on the drug by the end of the company’s 2023 fiscal year.
But how quickly sales increase will depend on Eisai and Biogen’s ability to address certain challenges. Estimates hold that roughly 6 million people in the U.S. have Alzheimer’s of any stage. If even a relatively small fraction are cleared to use Leqembi — a drug administered via an hour-long intravenous infusion every two weeks — the volume could overwhelm Alzheimer’s treatment centers.
Additionally, treatment with Leqembi requires considerable testing. To be eligible for the drug, patients must be positive for disease-causing amyloid beta and be diagnosed with either mild cognitive impairment or mild dementia due to Alzheimer’s. They also must undergo at least several MRIs before and during treatment to scan for “ARIA,” a known side effect of amyloid-target therapies that presents as swelling or micro-bleeding in the brain.
In the larger study that led to Leqembi’s full approval, around one-fifth of participants on the drug experienced ARIA. There were also three deaths in an extension portion of the study in which all participants received Leqembi. Researchers observed brain bleeding in two of those patients, and a “possible cerebrovascular accident” and severe ARIA in the third.
Leqembi’s new label includes a boxed warning — the most significant kind of warning a drug can carry — alerting patients and doctors to the potential risks associated with ARIA.
The safety risks have fueled debate among doctors about whether Leqembi is a net-positive for patients. Some see it as the most effective option yet for slowing a devastating disease, while others believe it offers marginal benefits at best.
According to Constantine Lyketsos, director of the Memory and Alzheimer’s Treatment Center at Johns Hopkins Medicine, Leqembi is “doing better than the placebo, but not much better.”
In an interview earlier this year, Lyketsos argued there appears to be a ceiling of effectiveness for even the more promising anti-amyloid drugs. Because of those limits, and the potential side effects, he said he is “certainly going to be very conservative at first” when prescribing medicines like Leqembi.
Costs may also be a concern for prescribers and patients. Medicare expects members on its original plan to pay 20% coinsurance of the Medicare-approved cost for Leqembi once they meet their Part B deductible. That could leave some patients on the hook for hundreds or thousands of dollars.
Medicare noted in a statement that costs may differ depending on whether patients have supplemental coverage or secondary insurance, or if they’re enrolled in a Medicare Advantage plan.
“With FDA’s decision, [the Centers for Medicare and Medicaid Services] will cover this medication broadly while continuing to gather data that will help us understand how the drug works,” said CMS Administrator Chiquita Brooks-LaSure.