Updated ICER Analysis Shows Leqembi Still Not Cost-Effective

The Institute for Clinical and Economic Review (ICER), in an updated evidence report, has calculated a health-benefit price benchmark (HBPB) for Biogen/Eisai’s Alzheimer’s treatment Leqembi (lecanemab) to be between $8,900 and $21,500 per year, which is lower than the Leqembi’s wholesale acquisition cost of $26,500 a year. ICER analysts said that Leqembi would need a 66% to 19% discount from its wholesale acquisition cost to fall within commonly used cost-effectiveness thresholds.

ICER’s health-benefit price benchmark is a price range suggesting the highest U.S. price a manufacturer should charge for a treatment, based on the amount of improvement in overall health patients receive from that treatment.

Leqembi is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody was approved in January 2023 under an accelerated approval to treat patients with mild cognitive impairment or mild dementia stage of disease. The accelerated approval was based on a surrogate marker, the ability to clear amyloid beta plaque in the brains of patients with Alzheimer’s disease.

David Rind, M.D.

“Current evidence strongly suggests that lecanemab mildly slows the loss of cognition in patients with early Alzheimer’s disease. However, given the risks of brain swelling and bleeding, particularly when lecanemab is used outside of clinical trials, we have some uncertainties as to whether the average benefits of lecanemab exceed its risks. At its announced list price, lecanemab exceeds typical thresholds for cost-effectiveness and, given the large number of patients with Alzheimer’s disease, it is particularly important that therapies for Alzheimer’s disease be priced in line with their value to patients,” David Rind, M.D., ICER’s chief medical officer, said in a press release.

At 18 months, the Leqembi-treated group showed a statistically significant 27% slowing of cognitive decline compared with placebo. But ICER analysts continue to be uncertain that amyloid removal is an appropriate surrogate outcome for clinical benefit. ICER researchers said there is not enough data to show that Leqembi’s removal of amyloid slows cognitive decline

They also express concern in the latest analysis that amyloid-related imaging abnormalities (ARIA) may be more severe in patients than in the trial population. Among participants treated with Leqembi, 21.5% experienced amyloid related imaging abnormalities with edema/effusion (ARIA-E), ARIA-hemorrhage or superficial siderosis (ARIA-H), or both compared with 9.5% in the placebo group, and 3.5% of patients in the Leqembi group experienced symptomatic ARIA-E or -H compared with 0.2% in the placebo group.

People with Alzheimer’s disease and their caregivers who spoke with ICER were concerned about brain swelling and questioned whether the gains in quality of life that might be seen with treatment outweighed that risk. There was also concerned about the disparities in clinical research. Although African Americans make up only around 9% of the U.S. population, they represent 13.8% of persons with dementia. But Black or African American and Hispanic or Latino people were underrepresented in the Leqembi studies; just 2.5% of patients enrolled in the CLARITY AD trial were black, for example. Black people with Alzheimer’s disease are more likely to experience neuropsychiatric symptoms, behavioral changes such as agitation and aggression, abnormal sleep, and motor disturbances.

Eisia and Biogen have submitted a supplemental biologics license application (sBLA) for full approval. The supplemental application is based on the data from the phase 3 confirmatory Clarity AD clinical trial. In Clarity AD, Leqembi met the primary endpoint and all key secondary endpoints with highly statistically significant results. In November 2022, the results of the Clarity AD study were presented at the 2022 Clinical Trials on Alzheimer's Disease (CTAD) conference, and also published in the Jan. 5, 2023, issue of The New England Journal of Medicine.

In this study, Leqembi reduced markers of amyloid in early Alzheimer’s disease and resulted in moderately less decline on measures of cognition and function than placebo at 18 months. But it also resulted in infusion-related reactions in 26.4% of the patients and amyloid-related imaging abnormalities with edema or effusions in 12.6% of patients. Serious adverse events occurred in 14.0% of the participants in the lecanemab group and 11.3% of those in the placebo group. The most commonly reported serious adverse events were infusion-related reactions. Adverse events leading to discontinuation of the trial agent occurred in 6.9% of the participants in the lecanemab group and 2.9% of those in the placebo group.