Biogen, a prominent pharmaceutical company, has become a significant force in Alzheimer’s disease treatment development. Historically, treatment options were limited. Biogen’s dedicated research and development efforts aim to address this unmet medical need by exploring new approaches to target the disease’s underlying pathology.
Aducanumab’s Development and Impact
Aducanumab, marketed as Aduhelm, was developed by Biogen and Eisai and received accelerated FDA approval in June 2021 for Alzheimer’s disease. This approval was based on its ability to reduce amyloid beta plaques in the brain, a surrogate endpoint. The decision sparked considerable debate due to conflicting results from its Phase 3 clinical trials, EMERGE and ENGAGE.
The EMERGE and ENGAGE trials were initially halted in March 2019 after a futility analysis suggested the drug was unlikely to show a clinical benefit. Biogen later re-evaluated the data, claiming a reduction in cognitive decline in EMERGE but not ENGAGE. Despite an FDA advisory committee voting overwhelmingly against its approval, citing insufficient evidence of clinical benefit, the FDA proceeded with accelerated approval. Biogen discontinued aducanumab’s development and commercialization in January 2024, citing a realignment of its Alzheimer’s disease franchise and limited real-world uptake.
Lecanemab’s Efficacy and Approval
Lecanemab, known by the brand name Leqembi, represents a subsequent development from the collaboration between Biogen and Eisai, showing more consistent results in slowing cognitive decline. It initially received accelerated FDA approval in January 2023, followed by full traditional approval in July 2023. The full approval was largely supported by data from the confirmatory Phase 3 Clarity AD study, which involved 1,795 participants with early-stage Alzheimer’s disease.
The Clarity AD study demonstrated that lecanemab met its primary endpoint, showing a statistically significant 27% reduction in cognitive decline as measured by the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score over 18 months compared to placebo. This reduction represented a delay in progression of approximately 7.5 months. Lecanemab’s safety profile includes Amyloid-Related Imaging Abnormalities (ARIA), which occurred in 21% of lecanemab-treated patients in Clarity AD, compared to 9% in the placebo group. Symptomatic ARIA, which includes headache or confusion, occurred in 3% of treated patients, with serious symptoms reported in 0.7%. These symptoms typically resolved over time, with 79% of symptomatic ARIA cases resolving during observation.
Understanding Amyloid-Targeting Therapies
Both aducanumab and lecanemab are monoclonal antibody therapies that operate on the amyloid hypothesis, a leading theory in Alzheimer’s disease research. This hypothesis suggests that the accumulation of amyloid-beta (Aβ) proteins in the brain, forming sticky plaques, is a primary driver of the disease’s progression. These plaques are believed to trigger a cascade of events leading to neuronal damage and cognitive decline.
Monoclonal antibodies like aducanumab and lecanemab are designed to target and clear these amyloid plaques from the brain. Aducanumab was developed with a greater affinity for high molecular weight amyloid species, while lecanemab specifically targets amyloid-beta protofibrils, which are considered particularly toxic to neurons. The mechanism of action involves the antibodies binding to these amyloid forms, initiating their removal through processes like microglial activation, where the brain’s immune cells help clear the protein aggregates. By reducing amyloid burden, these therapies aim to slow the underlying disease process rather than just managing symptoms.
Accessing Biogen’s Alzheimer’s Treatments
Accessing treatments like lecanemab involves specific eligibility criteria and diagnostic procedures to ensure appropriate patient selection. Treatment is generally indicated for individuals with mild cognitive impairment or mild dementia due to Alzheimer’s disease, as these are the populations studied in clinical trials. Confirmation of amyloid pathology in the brain is required, typically through an amyloid Positron Emission Tomography (PET) scan or cerebrospinal fluid (CSF) analysis.
The treatment is administered intravenously in a healthcare provider’s office or an outpatient setting, usually as a biweekly infusion. For Medicare beneficiaries, coverage for lecanemab is available if the patient meets the diagnostic criteria, including documented evidence of beta-amyloid plaques. Additionally, the treating physician and clinical team must participate in a qualifying registry to collect real-world evidence on the drug’s effectiveness. While Original Medicare Part B covers 80% of the Medicare-approved amount after the deductible is met, patients may still incur out-of-pocket costs, estimated to be around $5,000 annually, depending on their supplemental coverage.