In a landmark development in the fight against Alzheimer disease, the United States Food and Drug Administration (FDA) has granted full approval to the disease-modifying therapeutic lecanemab.
Alzheimer disease is a devastating neurodegenerative condition that affects millions worldwide. A key characteristic of the disorder is the presence in the brain of plaques that are made up of clumps of misfolded amyloid beta. Toxic species of this protein—called oligomers or protofibrils—are believed to disrupt brain cell function, eventually leading to memory loss and cognitive decline.
Most treatments for Alzheimer disease help to manage symptoms but do nothing to slow or halt disease progression. Lecanemab, on the other hand, is designed to target a fundamental disease process—the build-up of toxic amyloid beta species—to change the course of the disorder.
Lecanemab, marketed as Leqembi, is the second drug in a new class of anti-amyloid beta immunotherapies, which target toxic amyloid beta species, enabling their removal by the immune system.
Dr. Martin Ingelsson, a Senior Scientist and geriatrician at the Krembil Brain Institute, was an active member of the research team of Dr. Lars Lannfelt at Uppsala University in Sweden where the first steps in the development of lecanemab took place. He expressed his enthusiasm for the FDA announcement, saying the drug’s full approval “marks a significant milestone for patients and their families.”
“Alzheimer disease is relentless, and we have so far not had any good medications to offer. Lecanemab is a much-needed treatment option that we hope can make a difference to our patients.”
Since the partial approval of lecanemab by the FDA (through the Accelerated Approval pathway), a multinational phase III clinical trial led by pharmaceutical company Eisai Inc.—involving nearly 1800 patients—showed that the drug can significantly slow cognitive decline.
As the drug becomes available to more people, researchers will continue to study its long-term effects, optimal dosing regimens and potential use in combination with other therapies.
“Lecanemab is not a cure, and it comes with potentially serious risks for some patients,” cautions Dr. Ingelsson. But there is still a lot to be excited about. The relatively modest clinical effects seen in the clinical trial will hopefully be more pronounced when patients are treated for a longer period.
“We need to remember that Alzheimer disease occurs over decades. We hope that, over time, the drug could have a major impact on quality of life by preserving patients’ cognitive function and prolonging their independence.”
Beyond treating Alzheimer disease, lecanemab also represents a new strategy to manage other neurodegenerative conditions. In collaboration with Dr. Lannfelt and BioArctic AB—the Swedish biotech company behind the development of lecanemab—Dr. Ingelsson has been involved in the development of an antibody-based therapy for Parkinson disease, which was recently tested in a phase I clinical trial.
Dr. Martin Ingelsson, a Senior Scientist and geriatrician at UHN’s Krembil Brain Institute.
Similar to lecanemab, this therapy targets toxic forms of a protein, called alpha-synuclein, which accumulates in the brains of those living with Parkinson disease.
“Alzheimer disease and Parkinson disease share several molecular features, so general disease-modifying approaches that work in one condition could also work in the other,” explains Dr. Ingelsson.
In his lab at Krembil, Dr. Ingelsson has recently started a project focused on developing other therapeutic antibodies that could help address the diverse disease processes that are at play in individuals with Alzheimer disease and Parkinson disease.
“Different forms of amyloid-beta and alpha-synuclein are present in different patients, so personalized immunotherapies that selectively target specific protein variants could yield even greater benefits,” speculates Dr. Ingelsson.
For more information, click here to read the FDA announcement.
Dr. Martin Ingelsson is a paid consultant for BioArctic AB, the Swedish biotech company behind the development of lecanemab.