In the US, Eisai has made two key decisions that differ from Biogen’s troubled launch of Aduhelm: it has put the price of Leqembi at less than half the initial price of Aduhelm (with hopes to lower the price in the future); and has submitted a Supplemental Biologics License Application for traditional approval of Leqembi (in addition to the accelerated approval received on Friday) to aid with CMS coverage decisions in the US.
Supplemental Biologics License Application
On the same day it received FDA accelerated approval for Leqembi from the FDA (Friday 6 January), Eisai submitted an application for the traditional approval pathway (sBLA).
The accelerated approval of Leqembi was based on Phase 2 data that demonstrated the drug reduced the accumulation of Aβ plaque in the brain, a defining feature of AD. Continued approval for this indication is contingent upon verification of Leqembi’s clinical benefit in a confirmatory trial.
The sBLA for Leqembi, in contrast, is based on the data from the Phase 3 confirmatory Clarity AD clinical trial. Data presented in November showed Leqembi met the primary endpoint and all key secondary endpoints with ‘highly statistically significant results’. Meanwhile, the profile of Amyloid-Related Imaging Abnormalities (ARIA) incidence - an area of concern with anti-amyloid drugs - was ‘within expectations’.
Eisai serves as the lead of Leqembi development and regulatory submissions globally with both Eisai and Biogen co-commercializing and co-promoting the product and Eisai having final decision-making authority.
In April last year, the US Centers for Medicare & Medicaid Services (CMS) stated it would not cover anti-amyloid monoclonal antibodies for which the FDA had not determined clinical benefit - in this case those under accelerated approval - which such drugs only covered under NIH trials. Without CMS coverage, this decision has affected the fortunes of Biogen's (accelerated approval) Aduhelm.
Reacting to Friday's approval of lecanemab via the accelerated approval pathway, a statement from the CMS confirmed the drug will - for the moment - be treated in the same way as Aduhelm's accelerated approval.
"As announced in April 2022, CMS laid out how FDA-approved monoclonal antibodies directed against amyloid for the treatment of Alzheimer’s disease could be covered by Medicare. Because Eisai’s product, lecanemab, was granted accelerated approval by the FDA, it falls under CMS’s existing national coverage determination," said the CMS.
However, it continued: "CMS is examining available information and may reconsider its current coverage based on this review.
"If lecanemab subsequently receives traditional FDA approval, CMS would provide broader coverage using the framework we announced last year, under coverage with evidence development, on the same day. For FDA traditional approval the drug demonstrates evidence of efficacy from a direct measure of clinical benefit.
"The same would apply to any monoclonal antibody directed against amyloid for the treatment of Alzheimer's disease."
The CMS continues to engage with stakeholders on anti-amyloid coverage: in the April 2022 National Coverage Determination (NCD), CMS stated it was interested in data that could answer the following questions:
- Does the antiamyloid mAb meaningfully improve health outcomes (i.e., slow the decline of cognition and function) for patients in broad community practice?
- Do benefits, and harms such as brain hemorrhage and edema, associated with use of the antiamyloid mAb, depend on characteristics of patients, treating clinicians, and settings?
- How do the benefits and harms change over time?
US and rollout
Leqembi is indicated for the treatment of Alzheimer’s disease in patients with early AD.
Eisai (which is solely responsible for pricing in its partnership with Biogen), will put the US launch pricing at $26,500 per year. That compares to Aduhelm’s initial launch price of $56,000, and remains just under Aduhelm's price cut to $28,000.
In setting out its calculations, however, it estimates that the per patient, per year value of Leqembi treatment to society to be $37,000 (for example in terms of medical and associated costs). Working on the basis the drug can delay disease progression by nearly 3 years on average compared to standard-of-care, that puts the value of the drug at around $135,000 in lifetime value per patient to society, it says.
“Eisai decided to price Leqembi below quantified societal value at the wholesale acquisition cost (WAC) of $26,500 per year: aiming to promote broader patient access, reduce overall financial burden, and support health system sustainability," says the company.
In addition, it continues to pursue a less frequent maintenance dosing regimen for Leqembi - such as monthly instead of the current biweekly regimen.
“This could further lower the yearly cost of Leqembi during the maintenance dosing phase, for example, from $26,500 to potentially about half of this figure given less amount of drugs.”
Eisai champions affordability as a key necessity to promote patient access.
"Among the eligible Early AD patient population in the US, once the patient's insurer covers Leqembi, we estimate that approximately 91% of individuals will be covered by Medicare with Medigap (supplemental insurance), Medicare Advantage (Medicare-approved plans from private companies with potential supplemental coverage), Medicaid, and Commercial (private insurance12).
“For these patients, their out-of-pocket costs for Leqembi treatment could range from $0 to a few dollars per day. Remaining 9% of the individuals will fall into the category of Medicare without supplemental insurance, and hence will be responsible for 20% of the Leqembi cost as co-insurance under Medicare Part B. For these patients, their estimated out-of-pocket costs for Leqembi at the price of $26,500 per year will translate into about $14.50 per day.
“Across the entire eligible Early AD patient population, we estimate the weighted average out-of-pocket costs for Leqembi to be about $2 per day.”
Global rollout plans
Eisai initiated submission of data for BLA to the National Medical Products Administration (NMPA) of China in December 2022. It also plans to file for marketing authorization applications of lecanemab in Japan and EU by the end of March (a market where Biogen failed to win approval for Aduhelm).