NEW YORK – The Institute for Clinical and Economic Review (ICER), a nonprofit that conducts independent value assessments of healthcare interventions, remains unconvinced that the benefits of Biogen and Eisai's Alzheimer's disease drug Leqembi (lecanemab) are worth its cost.
Leqembi is the latest anti-amyloid therapy to be approved by the US Food and Drug Administration for Alzheimer's disease. In a report released earlier this week, ICER categorized treatment with Leqembi as "promising but inconclusive."
The FDA in January granted Leqembi accelerated approval based on its ability to clear amyloid — the surrogate biomarker that was also the basis for the FDA's controversial approval of Biogen and Eisai's Alzheimer's drug Aduhelm (aducanumab) in 2021. In a Phase III trial, however, in addition to clearing amyloid, Leqembi also improved patients' cognition. Leqembi-treated patients averaged a score of 1.21 on the Clinical Dementia Rating Scale-Sum of Boxes, while those on placebo had an average score of 1.66. The 0.45 difference in scores between the two groups translates to a 27 percent slower rate of cognitive decline for Leqembi-treated patients, Biogen and Eisai reported.
However, it's unclear whether that less than half a point difference in score results in noticeable improvements in patients' memory and other functions, according to ICER. On top of that, the group said in the report that they remain "uncertain" that amyloid clearance is an appropriate surrogate endpoint for clinical benefit in Alzheimer's patients.
ICER also expressed caution about amyloid-related imaging abnormalities (ARIA), an adverse event seen in 21.5 percent of trial participants treated with Leqembi and 9.5 percent in the placebo group. That incidence could be more severe outside of clinical trials "if, as expected, monitoring MRIs are not as frequent as in the clinical trial, the patient population treated differs from the trial population, and clinicians are less expert than those who participated in the randomized trial."
"In aggregate, the net health benefits of lecanemab in participants with early [Alzheimer’s disease] may be small or even substantial, but there remains a possibility of net harm from ARIA," ICER concluded. "We rate treatment with lecanemab in [mild cognitive impairment] due to [Alzheimer's disease] or mild [Alzheimer's disease] as 'Promising but Inconclusive.'"
The cost-effectiveness assessment body also raised concerns about Leqembi's per-year list price — $26,500 — and issued an access and affordability alert on the grounds that the added costs associated with the drug might be difficult for the healthcare industry to "absorb over the short term without displacing other needed services," creating pressure for payors. Based on an analysis of treatment effectiveness, possible adverse events, and other medical costs, as well as social considerations like patient productivity and time spent by caregivers, ICER said Leqembi's price would need to drop between 19 percent to 66 percent to reach a cost-effective price of $8,900 to $21,500.
In its own data modeling, Eisai expects Leqembi to delay Alzheimer's progression by an average of three years compared to standard of care, and as such, places the per-patient societal value of the drug at $37,600 per year. However, Eisai explained in a statement earlier this year that it decided to price Leqembi below its "quantified societal value" at $26,500 per year "to promote broader patient access, reduce overall financial burden, and support health system sustainability."
Still, there is currently limited Medicare coverage for Leqembi. Last year, the Centers for Medicare & Medicaid Services agreed to cover anti-amyloid monoclonal antibodies for Alzheimer's only when patients receive them within randomized clinical trials. Meanwhile, the Veterans' Health Administration has said it will cover Leqembi.
ICER's cost-effectiveness analyses are influential in policy circles, but its conclusions about Leqembi go against the views of patients who want broader access to the drug. The report comes a month after patients and caregivers organized by the Alzheimer's Association lobbied legislators in Washington, D.C., to urge Medicare to provide early access to new drugs, such as Leqembi.