By: Imaan Sekhery, PharmD Candidate c/o 2025
On January 6, 2023, the United States (U.S.) Food and Drug Administration (FDA) approved Eisai’s Leqembi (lecanemab), an alternative treatment for Alzheimer’s disease (AD). The creation of the drug depicts a significant advancement within the small field of AD treatments. This disease state is known to begin with memory loss, progressively leading to further unresponsiveness in an individual.1 Before the approval of lecanemab, cholinesterase inhibitors and N-methyl-D-aspartate (NDMA) antagonists were the main available treatment options for patients with AD.2 Lecanemab is under the class of monoclonal antibodies and intends to target the fundamental pathophysiology of AD.3 Lecanemab specifically targets amyloid beta plaques and neurofibrillary tangles, where the monoclonal antibody selectively binds to destroy amyloid-beta aggregate.4 This affects an individual’s ability to remember and think coherently. Consequently, the medication would be recommended to patients within the first or mild stages of AD to obtain maximal benefit. This will aid in reducing the damage done by amyloid beta plaques, slowing down the path to dementia and deterioration.
The final push for the FDA to approve lecanemab using the Accelerated Approval Program was Eisai’s phase 3, eighteen-month, double-blind, placebo-controlled trial. This study was conducted with patients ranging from the ages 50 to 90, involving 1,795 patients with early AD.4 Of the 1,795 patients, 898 were given lecanemab 10mg/kg twice a week while 897 were given placebo. The study was conducted in over 200 sites across North America, Europe, and Asia. The primary endpoint was the change in Clinical Dementia Rating Sum of Boxes (CDR-SB) score from baseline at 18 months. To further assess lecanemab’s functionality, changes from baseline in amyloid burden on Positron Emission Tomography (PET), AD Assessment Scale: Cognitive Subscale 14 (ADAS-cog142) score, AD Composite Score (ADCOMS) and AD Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-MCI-ADL) score. Higher CDR-SB, ADAS-cog142, and ADCOMS scores indicated greater impairment whereas the opposite was true of ADCS-MCI-ADL scores.4 As seen in Figure 1, after 18 months, the use of lecanemab was shown to slow the rate of worsening AD within the beginning stages of the disease as compared to a placebo. There was an approximately 27% slower decline compared to the patients on placebo (CDR-SB difference: -0.45; 95% confidence interval [CI] -0.67 to -0.23; p < 0.001). Lecanemab demonstrated consistency in efficacy across the other predefined subgroups as well. Even so, minor side effects arose, such as infusion-related reactions and amyloid-related abnormalities, occurring in 26.4% and 12.6% of the patients, respectively. Additionally, a previous phase 2b trial utilizing a Bayesian design proposed that the drug may be able to slow the rate of mental deterioration by 2.5 to 3.1 years while improving the quality of life of patients in early stages of AD along with the people surrounding them.5 The results from these studies are what led the FDA to accelerate the approval of this drug.
Although the FDA has only just approved lecanemab, there has already been controversy surrounding the price that the AD medication will be marketed. Alongside came “Eisai’s Approach to U.S. Pricing,” which took the societal value of medicine into account for the new price of the drug.6 The price of the drug was determined based on a wholesale acquisition cost goal of no more than $26,500 a year for the average patient, weighing 75kg and receiving 10mg/kg IV weekly of lecanemab.6 Eisai also addressed that once this medication become covered by insurance, approximately 91% of patients will be covered for this medication. The other 9% would have Medicare without supplemental insurance and would became responsible for 20% of the $26,000 cost or $14.50 a day.6 This pricing approach seems reasonable for the medication’s value in the U.S.
The accelerated approval of lecanemab for AD by the FDA seems promising, despite the shocking price tag attached. In 2020, over 5 million Americans were living with AD, which is suspected to triple by 2060.1 While also assisting health system sustainability, lecanemab would improve the quality of life of AD patients and their loved ones. Lecanemab will surely change the world of AD therapy for the better.
- Alzheimer’s disease and related dementias. Centers for Disease Control and Prevention. Last Update October 26, 2020. https://www.cdc.gov/aging/aginginfo/alzheimers.htm
- How is Alzheimer’s disease treatment? NIH National Institute of Aging. Last Updated July 8, 2021. https://www.nia.nih.gov/health/how-alzheimers-disease-treated.
- FDA grants accelerated approval for Alzheimer’s disease treatment. U.S. Food and Drug Administration. Published January 6, 2023. https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-alzheimers-disease-treatment.
- Eisai presents full results of lecanemab phase 3 confirmatory clarity ad study for early Alzheimer’s disease at clinical trials on Alzheimer’s disease (CTAD) conference. Eisai Global. Published November 30, 2022. https://www.eisai.com/news/2022/news202285.html.
- Swanson CJ, Zhang Y, Dhadda S, et al. A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer’s disease with lecanemab, an anti-Aβ protofibril antibody. Alzheimers Res Ther. 2021;13(1):80. doi:10.1186/s13195-021-00813-8
- Eisai’s Approach to U.S. Pricing for Leqembi™ (lecanemab), a treatment for early Alzheimer’s disease, sets forth our concept of “Societal Value of Medicine” in relation to “Price of Medicine”. Published January 7, 2023. https://www.eisai.com/news/2023/news202302.html.