Eisai present clinical data for continuous treatment with lecanemab at The Alzheimer’s Association International Conference 2024

Eisai has presented the latest findings for lecanemab at the Alzheimer’s Association International Conference (AAIC) 2024, held in Philadelphia, U.S., on 30 July 2024. In Europe, lecanemab is an investigational medicine for adults with early Alzheimer’s disease (AD) (mild cognitive impairment or mild dementia due to AD) with confirmed amyloid pathology.¹ The data presented at AAIC include:

• Clarity AD open-label extension (OLE) data show: three years of continuous lecanemab treatment reduced clinical decline by -0.95 vs expected decline based on the Alzheimer’s Disease Neuroimaging Initiative (ADNI*) group, on the global cognitive and functional scale Clinical Dementia Rating-Sum of Boxes (CDR-SB).²
• Clarity AD OLE data show: no new safety findings have been observed with continued lecanemab treatment over three years.²
• Phase 2b (Study 201) data show: after plaque is cleared and lecanemab treatment is stopped, AD progression rate of decline reverts to that of the placebo group.²

The dual-acting medicine is a humanised amyloid-beta (Aβ) monoclonal antibody that selectively binds to soluble Aβ aggregates (protofibrils**), as well as insoluble Aβ aggregates (fibrils) which are a major component of Aβ plaques in AD, thereby reducing both Aβ protofibrils and Aβ plaques in the brain.^1,2,3,4 Protofibrils are toxic and can continue to cause neuronal injury and death after plaques have been cleared from the brain.^2,5

Clarity AD OLE data show: three years of continuous lecanemab treatment reduced clinical decline by -0.95 vs expected decline based on the ADNI group, on the global cognitive and functional scale CDR-SB.²

Clarity AD was a global core Phase 3 placebo-controlled, double-blind, parallel-group, randomised study in 1,795 people with early AD (lecanemab group: 10 mg/kg bi-weekly IV treatment: n=898, placebo group: n=897).¹ In the Clarity AD core study, the primary endpoint was the change in the score of the global cognitive and functional scale, CDR-SB.¹ The primary end point was met with statistically significant results, of a difference of -0.45 with lecanemab vs placebo.¹ The mean CDR-SB score at baseline was approximately 3.2 in both groups. The adjusted least-squares mean change from baseline at 18 months was 1.21 with lecanemab and 1.66 with placebo.¹

Over 36 months of treatment across the core study and OLE (n=714), lecanemab reduced cognitive decline on the CDR-SB by -0.95 compared to the expected decline based on the ADNI group.² The adjusted mean change from baseline at 36 months in CDR-SB was 3.09 for patients receiving lecanemab for 36 months and 4.04 for the ADNI observational group.²

In the global Phase 3 Clarity AD core trial, the most common adverse events (>10%) in the treatment group were infusion reactions, ARIA-H, ARIA-E, headache, and fall.¹ Amyloid-related imaging abnormalities (ARIA) can be characterised by either oedema (a build-up of fluid) (ARIA-E^†) or haemorrhage (small bleeds) (ARIA-H^††).

Clarity AD OLE data show: no new safety findings have been observed with continued lecanemab treatment over three years.²

Most ARIA occurred in the first six months of treatment. Most patients who had ARIA had CDR-SB assessments after the event. Sensitivity analyses suggest that ARIA may not impact cognition or function.² The available information from the OLE at three years suggested that ARIA was not associated with accelerated long-term progression.²

Phase 2b (Study 201) data show: after plaque is cleared and lecanemab treatment is stopped, AD progression rate of decline reverts to that of the placebo group.²

Study 201 is a multicentre, double-blind, placebo-controlled, Phase 2b trial conducted in 856 patients with early AD.⁶ Appropriate patients participated in the OLE after an off-treatment period of 9-59 months (mean: 24 months) following the 18-month core study.⁷ During the off-treatment period lecanemab’s clinical effect was maintained but the rate of decline (slope) in patients who stopped lecanemab therapy reverted back to the rate of decline in patients on placebo as measured by CDR-SB.² The data indicates that after Aβ plaque removal, AD continues to progress, and reverts to the placebo rate of decline when treatment with the medicine is stopped.²

Eisai serves as the lead of lecanemab development and regulatory submissions globally with both Eisai and Biogen co-commercialising and co-promoting the product and Eisai having final decision-making authority.

*ADNI is a clinical research project launched in 2004 to develop methods to predict the onset of AD and to confirm the effectiveness of treatments. The ADNI observational cohort represents the exact population of those in the Clarity AD study; matched ADNI participants show similar degree of decline to placebo group out to 18 months.^2,8,9

**Protofibrils are large Aβ aggregated soluble species of 75-5000 Kda.^3,4,10

^†ARIA-E: amyloid-related imaging abnormalities with oedema (oedema/effusion) 

^††ARIA-H: amyloid-related imaging abnormalities with haemorrhage (combined cerebral microhaemorrhages, cerebral macrohaemorrhages, and superficial siderosis)

About AD and CDR-SB

AD is a neurodegenerative disease that progresses in stages and increases in severity over time.¹¹ People living with AD can experience a loss of cognition, memory and independence, which may impact different areas of daily life.^11,12

A commonly used diagnostic tool, which can help to stage dementia due to AD, is the CDR-SB.¹² It is a global cognitive and functional scale that measures six domains of functioning, including memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care.¹²

A change of 0.5 to 1 on the CDR score domains of Memory, Community Affairs and Home/Hobbies can be the difference between slight impairment and loss of independence, such as people’s ability to be left alone, remember recent events, participate in daily activities, complete household chores, function independently and engage in hobbies and intellectual interests.¹²

About Eisai EMEA

At Eisai, we give our first thought to patients, their care partners and to society, and to increase the benefits health care provides them – we call this human health care (hhc). We focus beyond the realm of health to the value we bring to society. Through the power of collaboration and by using insights to guide our work, we can make a meaningful contribution to people and society, and to improve outcomes and services for all.

In EMEA, we are the European hub of Tokyo-based Eisai Co. Ltd., forming part of a multinational team working across a global network of R&D facilities, manufacturing sites and marketing subsidiaries. 

Our collective passion and dedication to patient care is the driving force behind our efforts to discover and develop innovative medicines in a variety of therapeutic areas where a high unmet medical need remains, including oncology and neurology.

Our mission is clear; we strive to make a significant long-lasting contribution to society in an ethical, compliant, and sustainable way by embodying human health care in everything we do.

For more information about Eisai in the EMEA region please visit www.eisai.eu.

For more information about the data presented at AAIC please contact the Eisai EMEA communications team (emea-comms@eisai.net).