In this author’s opinion, this drug shows promise but isn’t quite ready.

By Raad Shakir, CBE FRCP

Raad Shakir

The whole world continues to wait for neuroscientists to come up with an effective treatment for Alzheimer’s disease. The condition attracts huge public interest, and there is intense focus on treatment availability. The “accumulation of soluble and insoluble aggregated amyloid-beta (Aβ) may initiate or potentiate pathological processes in Alzheimer’s disease. Lecanemab, a humanized IgG1 monoclonal antibody that binds with high affinity to Aβ soluble protofibrils, was tested in persons with early Alzheimer’s disease.”¹

Neurologists had been waiting for the double-blind study confirming the efficacy of lecanemab in early Alzheimer’s and mild cognitive impairment (MCI). Alzheimer’s is the main cause of dementia with a high mortality needing huge resources globally. By 2050, the prevalence of dementia will double in Europe and triple globally.² There is therefore an urgent global need to come up with a medication that is reasonably inexpensive, easy to transport, easy to administer, and widely available to counter this deadly pandemic.

The world as well as neurologists were rather optimistic when lecanemab passed its approval hurdle with the U.S. Food and Drug Administration (FDA).³ This approval came despite a black box safety warning because of side effects. This was soon followed by statements from the European Medicines Agency (EMA)⁴ and more recently the National Institute for Health and Care Excellent (NICE) of England and Wales. Both clearly stated that benefits of lecanemab are “just too small” to justify cost.⁵ However, the EMA revised its earlier decision to approve lecanemab in a small group that has one or no copy of the ApoE4 gene.⁶

Lecanemab must be administered by intravenous infusion in the hospital every two weeks. The individuals need to undergo exhaustive assessments. The clinical examination requires specialists in cognitive neurology, detailed psychology examinations, and imaging. The latter requires repeated MRI scanning before commencement and during treatment. Amyloid positron emission tomography (PET) is needed before and following the treatment. Physicians will need to have access to a cyclotron to obtain the isotope. All this is in addition to the cost of the drug, which is approximately $26,500 per patient per year.

Intense monitoring is required to detect amyloid related imaging abnormalities (ARIA) such as brain swelling and bleeding. ARIA is usually asymptomatic, although rarely serious, and life-threatening events can occur. Serious intracerebral hemorrhaging greater than 1 cm have occurred in patients treated with this class of medications.

Looking at the bare facts, lecanemab reduces the amyloid load significantly.¹ However, the improvement in cognitive decline in the trial of those with MCI and early Alzheimer’s disease was modest, with a 27% reduction of decline after 18 months compared to placebo. This equates to slowing in disease progression of between four and six months.

All that said, there is no doubt that we could be seeing the dawn of Alzheimer’s disease treatment, albeit with a rather cumbersome drug with many side effects at an exorbitant cost. •

Dr. Raad Shakir is a professor in the Division of Brain Sciences at Imperial College in London. He is a previous WFN president and current chair of the WFN Nomination Committee.