Monoclonal Antibody Lecanemab Finalizing Clinical Trials for Alzheimer’s Disease Treatment

Lecanemab, the product of Phase IIb clinical research completed by BioArctic and collaborator Eisai, is one therapy making strides this year for Alzheimer’s disease.

Alzheimer’s disease (AD) is a progressive neurodegenerative disease, with the most recognizable and common symptom of AD being amnesia-like cognitive impairment, such as short-term memory loss. Earlier manifestations of the disease are referred to as mild cognitive impairments (MCI), where the individual may have some cognitive functions impaired but can continue with everyday activities.

The severity of the disease can vary and progress through moderate to severe stages of dementia, at which point the individual may rely on a caregiver to perform daily activities. AD is prevalent, with approximately 1 in 14 Americans over the age of 65 being diagnosed. The main pathological markers of AD are beta-amyloid (Aβ) plaques and neurofibrillary tangles, which accumulate between and inside neurons, respectively, disrupting their function. This year, the monoclonal antibody lecanemab is approaching final stages of investigation as a treatment for targeting the Aβ plaques.

Plaque-neutralizing Capabilities of Lecanemab Slow Disease Progression

Disease-modifying therapies that can target the mechanisms behind the progression of AD to slow that progression are increasingly being studied as treatment options. Lecanemab, the product of Phase IIb clinical research completed by BioArctic and collaborator Eisai, is one such therapy making strides this year.

Lecanemab targets AD mechanisms by selectively binding to and neutralizing the accumulating Aβ plaques, interfering with their toxicity to the brain and slowing disease progression. The Phase IIb clinical trial focused on the long-term clinical outcomes and safety for patients with MCI and amyloid pathology (early AD). A disease simulation model was created based on the results of the clinical trial and published literature to understand the long-term benefits of lecanemab use.

The treatment arm of the study (lecanemab paired with the standard of care, memantine) was compared to a placebo arm (memantine alone). The simulation follows patients during their treatment until they progress to moderate AD. Overall, the model predicted an increased survival rate when lecanemab was used in treatment, and because of the prolonged duration of time spent in milder stages of AD, there is a lower likelihood of transitioning to severe AD or requiring institutional care.

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The Impact of Lecanemab

The results of this clinical trial are promising and provide insight beyond its clinical value — Gunilla Osswald, CEO of BioArctic, states that “analyses such as these are important to understand the potential long-term effects for patient, families and society offered by lecanemab treatment beyond what can be seen in clinical trials.”

The modelling from the Phase 2b study demonstrated that patients treated with lecanemab were maintained at earlier stages of AD for longer periods of time (ranging from 2.34 to 3.13 years depending on the severity of AD at the start of treatment). Delaying the onset of severe AD improves patient quality of life since they can manage daily activities with more ease. The results of this modeling can inform healthcare practitioners about the clinical, economic and social value of lecanemab as a treatment.

Next Stages in Clinical Research

Presently, Eisai expects a submission of a Biologics License Application (BLA) to the US Food and Drug Administration (FDA) for lecanemab for the treatment of early AD in the second quarter of 2022. Additionally, there are two ongoing Phase III clinical trials that are expected to be completed by the end of September 2022. The Clarity AD trial follows the treatment of symptomatic, early AD patients with lecanemab, and the AHEAD 3-45 trial similarly follows patients who are still asymptomatic but have elevated amyloid plaque levels. The treatment appears promising in terms of safety as well, with only mild or moderate reactions reported for infusions.