Clarity-AD-OLE Study in Alzheimer’s Disease

EP: 1.Presentation of Alzheimer’s Disease in Clinical Practice

EP: 2.Diagnosis and Treatment of Alzheimer’s Disease

EP: 3.Lecanemab for Treatment of Early Alzheimer Disease

EP: 4.ARIA With Monoclonal Antibody Treatments for Alzheimer Disease

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EP: 5.Clarity-AD-OLE Study in Alzheimer’s Disease

EP: 6.Continuous Dosing of Lecanemab for Alzheimer’s Disease

EP: 7.Donanemab for Treatment of Alzheimer’s Disease

EP: 8.Biomarkers in Alzheimer’s Disease (May 2025)

EP: 9.Emerging Agents in Alzheimer’s Disease

Summary for Physicians

Clarity AD Open-Label Extension (OLE): Longer-Term Efficacy and Safety of Lecanemab

The Clarity AD core study established the clinical efficacy of lecanemab in slowing cognitive and functional decline in early Alzheimer’s disease over an 18-month period. In 2024, interim results from the open-label extension (OLE) were published, providing critical insights into long-term use.

Comparison: Efficacy and Safety — OLE vs. Core Study

Efficacy Findings:

• Sustained Slowing of Disease Progression: Patients who continued lecanemab in the OLE maintained slower rates of cognitive decline (CDR-SB, ADAS-Cog, and ADL scales) compared to historical placebo.
• Early Initiation Advantage: Those originally randomized to lecanemab in the core trial had better long-term outcomes than those who initiated treatment in the OLE phase, supporting early treatment initiation.
• Amyloid Reduction Maintained: Amyloid PET imaging showed persistent low levels of amyloid plaque in patients who completed the core study, with minimal re-accumulation during the OLE.

Safety Findings:

• ARIA Incidence Remained Manageable:
  • No significant increase in ARIA-E or ARIA-H rates over time.
  • Most ARIA events occurred early, consistent with the initial treatment period.
• Symptomatic ARIA rates remained low, especially when monitoring protocols were followed.
• No new safety signals were identified in extended use.

Clinical Implications

• Supports Continuous Therapy: Long-term lecanemab use appears to sustain benefit without cumulative toxicity, supporting ongoing therapy in appropriate patients.
• Reinforces Early Diagnosis and Treatment: Patients starting earlier show better outcomes over time.
• Ongoing Monitoring Still Essential: Regular MRIs and clinical assessments remain necessary due to continued, albeit reduced, ARIA risk.

Key Takeaway

The Clarity AD OLE confirms that lecanemab’s benefits on cognition and function are durable, and that safety remains consistent with the core study. These findings strengthen the rationale for early and sustained use of amyloid-lowering therapies in Alzheimer’s disease.