February 22, 2023

FDA approves Alzheimer’s agent Leqembi shortly after release of congressional Aduhelm report

Less than two years after the FDA approved the first treatment for Alzheimer’s that was aimed at targeting the underlying disease process, it has approved a second similar agent. Payers are likely to cover the drug, one industry expert says, but they almost certainly will try to place restrictions on their coverage.

On Jan. 6, the FDA gave accelerated approval to Eisai Co., Ltd. and Biogen Inc.’s Leqembi (lecanemab-irmb) for the treatment of Alzheimer’s disease in people with mild cognitive impairment or mild dementia stage of disease. People must have confirmed presence of amyloid beta pathology before starting treatment. The agency gave the humanized immunoglobulin gamma 1 monoclonal antibody fast track, priority review and breakthrough therapy designations.

The agent will be available “during or before the week of” Jan. 23.

The wholesale acquisition cost for a 200 mg vial is $254.81, and the WAC for a 500 mg vial is $637.02. Eisai estimates that the average annual WAC will be $26,500.

The price is above the cost-effectiveness range set by the Institute for Clinical and Economic Review (ICER) in a Draft Evidence Report released Dec. 22. According to the group, “the prices needed to meet traditional cost-effectiveness thresholds for lecanemab, across various analytic perspectives and measures of benefit, range between $8,500 and $20,600 for a year’s course of treatment.”    

Approval Followed Release of Congressional Report.

The approval marks the second Alzheimer’s treatment for the two companies, following the June 7, 2021, controversial accelerated approval for Aduhelm (aducanumab-avwa) and that drug’s initial average price tag of $56,000, which later was cut in half. Leqembi’s approval also came shortly after the Dec. 29 release of a congressional report on the approval of Aduhelm and Biogen’s “aggressive launch plans” following an 18-month investigation by the U.S. House of Representatives’ Committees on Oversight and Reform, and Energy and Commerce.

“The findings in this report raise serious concerns about FDA’s lapses in protocol and Biogen’s disregard of efficacy and access in the approval process for Aduhelm,”concluded the report. “The findings also justify experts’ and stakeholders’ concerns about FDA’s accelerated approval of Aduhelm. The criticism surrounding Aduhelm’s approval may have been avoided had FDA adhered to its own guidance and internal practices. FDA must take swift action to ensure that its processes for reviewing future Alzheimer’s disease treatments do not lead to the same doubts about the integrity of FDA’s review. Biogen, which currently has another Alzheimer’s drug under review by FDA, must provide more transparency into its pricing and analyses of clinical benefit to ensure that new drugs are effective and available for those who need them.”

Eisai did exactly that: When the company unveiled the price, it shared the reasoning behind its decision, specifically its concept of “‘societal value of medicine’ in relation to ‘price of medicine.’” It concluded that the per-patient per-year value of treatment with Leqembi in the U.S. is $37,600 but that it had priced the drug “below quantified societal value.” The company also revealed that it was studying less frequent maintenance dosing, and, if found to be effective, such a regimen could lower the cost of the drug.

We deeply believe that our pricing approach to maximize value for all stakeholders will help Eisai achieve social good in the form of relieving anxiety over health and reducing health disparity according to our corporate philosophy,” maintained the company.

Eisai Will File Supplemental Application for Traditional Approval Soon

The data on which the FDA based its accelerated approval of Leqembi were from the Phase II Study 201, which showed that the drug decreased amyloid beta plaque. But on Sept. 27, Eisai and Biogen reported that the drug’s Phase III confirmatory Clarity AD clinical trial met its primary endpoint “and all key secondary endpoints with highly statistically significant results.” More specifically, lecanemab “reduced clinical decline on the global cognitive and functional scale, CDR-SB [i.e., Clinical Dementia Rating-Sum of Boxes], compared with placebo at 18 months by 27%.”

Eisai, said the release, was planning to discuss the data with the FDA “with the aim to file for traditional approval in the U.S.” by the end of the company’s 2022 fiscal year on March 31, 2023. In its press release announcing approval of the drug, the FDA acknowledged those study results and said it “anticipates receiving the data soon.”

On April 7, 2022, CMS released a final National Coverage Determination (NCD) stating that Medicare would cover monoclonal antibodies targeting amyloid for Alzheimer’s disease treatment that receive traditional FDA approval under coverage with evidence development (CED). Drugs receiving accelerated approval or that have not shown a clinical benefit will be covered in FDA- or National Institutes of Health-approved trials.

Currently, Medicare beneficiaries do not have access to Leqembi, Eisai and Biogen noted in a press release. However, CMS acknowledged the drug’s approval in a statement and said that it “is examining available information and may reconsider its current coverage.” It also stated that if the FDA grants Leqembi traditional approval, that Medicare would begin covering the drug under CED “on the same day.”

Asked about the significance of Leqembi’s approval, Ira Studin, Ph.D., M.P.H., principal at Stellar Managed Care Consulting, LLC, replies that “payers focus on clinical significance, and the ultimate arbiters of clinical significance are subject matter experts in the field. Data publicly available suggests it slowed disease progression by 27%. Given current standard of care, I would guess — despite continued uncertainty about the amyloid thesis — it does meet that threshold.”

“Expanding treatment options with Leqembi (lecanemab) for people living with Alzheimer’s disease is a great first step forward,” says Frank Amato, president and CEO of Synaps Dx, an Alzheimer’s disease diagnostic company that offers the Discern test, which can help identify Alzheimer’s. In clinical trials, it showed more than 95% sensitivity and specificity for identifying the condition. “We are excited about the prospect of adding a disease modifying therapy to the clinician’s armamentarium for this debilitating disease.”

While Studin acknowledges that Leqembi’s price is beyond ICER’s cost-effectiveness standard, “the devil is in the population size,” he tells AIS Health, a division of MMIT. “If Medicare payers commit to requiring rigorous documentation of early stage disease, $26,000 from a budget impact perspective may be acceptable because the volume won’t be there. However, there is also the issue of PET scans required for diagnosis, and those costs run in the thousands of dollars.”

He says he expects that payers will cover the new agent, “but I expect they will use all the latitude they have to be as restrictive as possible” both for initial authorization and subsequent reauthorizations. “If, for example, they want to adopt a tighter-than-label policy, they would need CMS approval, and that, in itself, will take time, which could mean no approvals until the plan gets closure on their request.

“One of the issues that does not appear to be discussed in the reporting is the impact of utilization on current private payer, MA-PD [i.e., Medicare Advantage prescription drug plan] budgets,” continues Studin. “Budgets are set, based on past experience, and I would guess 2023 payments from CMS do not reflect new product entrants for Alzheimer’s disease. However, I’m sure the budget impact issue for MA-PDs is being discussed by CMS.”

CMS’s NCD “is likely to be a major factor” in payer considerations for coverage, says Studin. “That’s why, if I understand current reporting, the manufacturer is planning their ‘scale up’ in launch strategy, not for the initial accelerated approval phase but for after, when they anticipate full approval.”

Contact Amato via Caroline Chambers at and Studin at

By Angela Maas

Provided by AISHealth – visit