FDA Converts Lecanemab-irmb to Full Approval for Treatment of Alzheimer Disease

The FDA has converted the accelerated approval of lecanemab-irmb (Leqembi) to a full traditional approval for the treatment of Alzheimer disease (AD) in patients with mild cognitive impairment or mild dementia state of disease.¹ Lecanemab-irmb is the first amyloid beta-directed antibody to be converted from an accelerated approval to a traditional approval for the treatment of AD.¹

“Today’s action is the first verification that a drug targeting the underlying disease process of [AD] has shown clinical benefit in this devastating disease,” Teresa Buracchio, acting director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, said in a statement. “This confirmatory study verified that it is a safe and effective treatment for patients with [AD].”¹

On June 9, the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee affirmatively voted that the results of the study verified the clinical benefit for the indicated use of lecanemab.¹ The traditional approval was based on a phase 3 randomized, controlled CLARITY AD clinical trial (NCT03887455), confirming the clinical benefit to patents.¹

Investigators evaluated the efficacy of lecanemab-irmb in a study of 856 individuals with AD. The treatment was started for those who had mild cognitive impairment or mild dementia stage of the disease and a confirmed presence of amyloid beta pathology, which is a marker of AD. Individuals received the approved dose of lecanemab-irmb 10 mg/kg every 2 weeks.²

Amyloid beta plaque was quantified using positron emission tomography imaging to estimate the levels of amyloid beta plaque within the regions of the brain expected to be affected by AD compared to other brain regions.² The results demonstrated a statistically significant and clinically meaningful reduction of decline from baseline to 18 months on the primary endpoint of the Clinical Dementia Rating Scale Sum of Boxes score compared to the placebo.¹

Additionally, there were statistically significant differences for all secondary endpoints, including Alzheimer’s Disease Assessment Scale Cognitive Subscale 14 and the Alzheimer’s Disease Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment.¹ Individuals who received the treatment had significant dose- and time-dependent reductions of amyloid beta plaque. The dosage resulted in a statistically significant reduction in brain amyloid plaque from baseline to week 79 compared to the placebo arm, where there were no reductions.²

However, there were safety concerns reported for a potential association with certain serious adverse events (AEs), including brain swelling and bleeding.Serious AEs were reported in 14% of patients in the lecanemab-irmb cohort and 11.3% in the placebo cohort.²

The most common AEs associated with lecanemab-irmb were infusion-related reactions, including flu like symptoms, nausea, vomiting, and changes in blood pressure. There were also reaction including amyloid-related imaging abnormalities (ARIA).²

ARIA tends to be symptomless, although serious and life-threatening events rarely occur. It can include temporary swelling of the brain that usually resolves over time, but may include small sports of bleeding.³

The FDA approves drugs under the accelerated pathway for serious conditions in which there is an unmet medical need, and a drug is shown to have an effect on a surrogate endpoint that predicts a clinical benefit to patients.³ Previously, the FDA voted unanimously that data from the clinical trial confirmed the clinical benefit of lecanemab-irmb for intravenous use in the treatment of AD.

The committee members also confirmed the overall benefit-risk profile of the drug, with clinically meaningful data. They discussed its use in specific subgroups, including those with Apolipoprotein E (ApoE) ε4 homozygote, those requiring concomitant treatment with anticoagulant agents, and those with cerebral amyloid angiopathy.⁴

The prescribing information now includes guidance about the ApoE ε4 allele and usage with anticoagulant agents, stating that testing for this the ApoE ε4 allele should be performed prior to treatment to assess the risk of ARIA.¹ Additionally, caution is recommended when using the drug for those who are taking anticoagulants or have other risk factors for intracerebral hemorrhaging, as this can increase the risk.¹

The results of the study were published in The New England Journal of Medicine.²

References

1. FDA converts novel Alzheimer’s disease treatment to traditional approval. FDA. July 6, 2023. Accessed July 6, 2023. https://www.fda.gov/news-events/press-announcements/fda-converts-novel-alzheimers-disease-treatment-traditional-approval
2. Hunter E. FDA grants accelerated approval to lecanemab for early stage Alzheimer disease. Pharmacy Times. January 6, 2023. Accessed July 6, 2023. https://www.pharmacytimes.com/view/fda-grants-accelerated-approval-to-lecanemab-for-early-stage-alzheimer-disease
3. FDA grants accelerated approval for Alzheimer’s disease treatment. News release. FDA. January 06, 2023. Accessed July 6, 2023. https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-alzheimers-disease-treatment
4. FDA Advisory Committee votes unanimously to confirm the clinical benefit of Leqembi (lecanemab-irmb) for the treatment of Alzerhimer’s diease. News release. Eisai. June 9, 2023. Accessed July 6, 2023. https://media-us.eisai.com/2023-06-09-FDA-Advisory-Committee-Votes-Unanimously-to-Confirm-the-Clinical-Benefit-of-LEQEMBI-R-lecanemab-irmb-for-the-Treatment-of-Alzheimers-Disease?_ga=2.81830486.1163536705.1688676971-219996024.1688676971