Developing disease modifying treatments against Alzheimer’s disease
Epidemiology and current treatments
Alzheimer’s Disease is a neurodegenerative disease affecting millions of patients, and their loved ones, around the world. To date, about 30 million individuals live with Alzheimer’s disease at different stages. The disease is characterized by death of neurons in the brain causing a progressive deterioration of memory and cognitive skills, such as intellectual ability, language, orientation, recognition and learning ability. The disease can lead to personality changes and psychiatric symptoms, for example; apathy, depression, disorientation, paranoia, aggressiveness, and motor symptoms, such as stiffness, reduced mobility and impaired responsiveness.
Research has long faced major challenges in developing effective drugs against Alzheimer’s disease, and patients have had to settle for treatments that only temporarily alleviates the symptoms. But, over the past decade, science has made important discoveries that form the foundation for a new era of treatments that impact the cause of the disease.
BioArctic’s research is at the forefront of this development, and our most advanced drug candidate lecanemab has the potential to become one of the world’s first drugs that not only alleviate the symptoms but also slow the underlying progression of the disease.
The cause of Alzheimer’s disease is believed to lie in the misfolding and aggregation of the amyloid-beta protein, resulting in the formation of soluble toxic aggregated forms. Importantly, the monomeric form of amyloid-beta present in most tissues and body fluids, is described as harmless. But in Alzheimer’s disease, the monomeric amyloid-beta forms aggregates. These aggregates grow in size an eventually form insoluble fibrils that accumulate in brain tissue as plaques.
The result of our ground-breaking research shows that the specific forms of soluble aggregated amyloid-beta species, known as oligomers and protofibrils, are the most harmful forms to nerve cells. Our engineered antibodies produced using well implemented strategies target these and other harmful forms of amyloid-beta in very specific ways.
BioArctic has eight drug projects for treatment of Alzheimer’s disease which approach the underlying pathologies in different ways, of which the drug candidate lecanemab, is the most advanced.
Lecanemab aims to slow the progression of Alzheimer’s disease
Lecanemab is an antibody targeting oligomers and protofibrils, the most harmful forms of Ab. Since 2007, lecanemab and its backup compound (Lecanemab back-up) is licensed to Eisai.
In September 2022, lecanemab showed positive results in the pivotal Phase 3 study, Clarity AD, in early Alzheimer’s disease, and both the primary and all key secondary endpoints were met with high statistical significance. Lecanemab was granted accelerated approval as a treatment for Alzheimer’s disease by the U.S. Food and Drug Administration (FDA) on January 6, 2023. On the same day, Eisai submitted a Supplemental Biologics License Application (sBLA) to the FDA for approval under the traditional pathway. In Europe, Eisai submitted a marketing authorization application (MAA) to the European Medicines Agency (EMA) on January 9, 2023, which was accepted on January 26, 2023. In Japan, Eisai submitted a marketing authorization application to the Pharmaceuticals and Medical Devices Agency (PMDA) on January 16, 2023, which was designated for Priority Review by the Japanese Ministry of Health, Labour and Welfare (MHLW) on January 30, 2023. In China, Eisai initiated submission of data for a BLA to the National Medical Products Administration (NMPA) in December 2022.
In addition to the pivotal Phase 3 study, there is ongoing open-label Phase 3 and Phase 2b extension studies with lecanemab and a further Phase 3 study (AHEAD 3-45) in persons who have not yet developed symptoms of Alzheimer’s disease but have intermediate or elevated amyloid levels in the brain.
Five additional antibodies under development
We are also conducting research into generating new antibodies intended for treatment of Alzheimer’s disease with the goal of slowing or stopping disease progression with innovative molecules that have different mechanisms of action. We have six additional antibody projects against Alzheimer’s disease in the project portfolio, all of which are in the research phase.
In particular, the project AD1503, is an antibody project against shorter, truncated forms of amyloid-beta that appear early on in the course of the disease and have a pronounced ability to aggregate and create harmful forms that could cause Alzheimer’s disease. The AD-BT2802 and AD-BT2803 drug projects are two antibody projects against Alzheimer’s disease that are being combined with our blood-brain barrier technology – Brain Transporter, or BT – to promote uptake of antibodies into the brain.
Lecanemab – Alzheimer’s disease
Lecanemab is an antibody that binds selectively to oligomers and protofibrils of amyloid-beta, which permits direct clearance and the body’s immune system to identify and eliminate them. Thereby, these toxic forms are thus cleared from the brain tissue and the progression of the disease is slowed. The high degree of selectivity against amyloid-beta oligomers and protofibrils – the most harmful forms – is unique to lecanemab. Importantly, the antibody binds 1,000 times more strongly to the harmful forms than to the harmless amyloid-beta monomers. This points to its potential as an effective drug candidate with potentially few side effects. Since 2007, lecanemab has been outlicensed to Eisai, the global Japanese pharma company, for Alzheimer’s disease.
Lecanemab Back-up – Alzheimer’s disease
Lecanemab back-up is a disease modifying antibody treatment for patients with early Alzheimer’s disease in partnership with Eisai. The drug candidate has a high selectivity for the toxic amyloid-beta oligomers/protofibrils. Lecanemab back-up is in late preclinical phase and BioArctic’s partner Eisai is driving the program towards clinical development.
AD1502 – Alzheimer’s disease
AD1502 is an innovative project to develop a disease modifying treatment for prodromal and mild Alzheimer’s disease.
AD1503 – Alzheimer’s disease
AD1503 is an innovative project to develop a disease modifying treatment for prodromal and mild Alzheimer’s disease. It is an antibody project against a shorter (truncated) form of amyloid-beta, which has a pronounced ability to aggregate and create toxic forms that could cause Alzheimer’s disease.
AD2603 – Alzheimer’s disease
AD2603 is part of BioArctic’s innovative drug development of new antibodies for the treatment of Alzheimer’s disease aimed at slowing down or stopping disease progression by addressing novel targets.