Our antibody humanisation work played an important part in the discovery of lecanemab, an experimental drug that has shown small but clear benefits for people with early Alzheimer’s disease.
In October, topline results of a landmark phase 3 clinical trial were announced which showed lecanemab slowed down cognitive decline – confusion or memory loss – in people with early Alzheimer’s. The clinical trial results were then published in New England Journal of Medicine in November and was heralded as a ‘historic moment’ – as lecanemab is the first treatment that’s ever been shown to slow the course of dementia.
LifeArc scientists collaborated with biotechnology company BioArctic Neuroscience to humanise the monoclonal antibody targeting a toxic form of a protein called amyloid beta that builds up in the brains of Alzheimer’s patients. This antibody ultimately became lecanemab.
Should lecanemab go on to receive approval (edit: it was subsequently approved by the FDA in January 2023), it could offer an effective treatment option for people with early signs of dementia – offering hope to millions of patients and their families around the world.
Alzheimer’s disease is the most common type of dementia, affecting more than half a million people in the UK. It is an irreversible, progressive brain disorder that slowly destroys memory, thinking and language skills. Sadly, there are currently no treatments that can prevent, slow down or reverse the disease.
One of the hallmarks of Alzheimer’s disease is the build-up of abnormal structures called ‘amyloid plaques’ in the brain. For many years, a great deal of research has focused on the amyloid hypothesis, which assumes that these plaques have a role in damaging brain cells and causing cognitive decline. But several other drug candidates that break down these toxic plaques in the brain have failed in late-stage clinical trials, which had led many to question whether this was the right approach.
In 2006, LifeArc partnered with BioArctic to sequence and ‘humanise’ their mouse monoclonal antibody mAb158, which targeted a specific form of the amyloid beta protein called protofibrils. This work generated the clinical candidate BAN2401, or lecanemab.
The results of the latest trial, which involved around 1,800 patients with early-stage Alzheimer’s disease, showed that the cognitive abilities of people who received lecanemab declined by 27% less than those on the placebo after 18 months. While the effects were small, with the potential for some significant side effects, it’s the first time that any treatment has been shown to offer help to people affected by this devastating disease.
The trial led to the FDA granting accelerated safety and regulatory approval for lecanemab in January 2023. On learning this news, LifeArc’s Chief Scientific Officer Dr Dave Powell said:
“We are delighted that lecanemab has been approved by the FDA as a treatment for people with a confirmed diagnosis of mild cognitive impairment or early-stage Alzheimer’s disease and are proud to have had a role in its discovery. The decision means doctors in the US will be able to prescribe the drug to people who can afford to pay for the drug directly or have appropriate medical insurance.
This news offers hope to millions of patients and their families around the world, as it’s the first drug to show a cognitive clinical benefit for people affected by this devastating condition. We hope the UK’s medicines regulator will make a quick decision on the drug, so eligible people in the UK can also benefit from this new medicine if the benefits for people with Alzheimer’s disease are clear and they are not outweighed by safety concerns.”
Testament to our expertise
Our scientists have extensive experience in antibody humanisation, which involves replacing the mouse regions of the antibody with human sequences until only the most critical parts remain that are of mouse origin. This reduces the chances of the patient’s immune system recognising the antibody as ‘foreign’ and rejecting it.
We have successfully humanised more than 90 therapeutic antibodies, including four that are now approved treatments and four in clinical trials.
On hearing the results of the phase 3 trial, Dr Preeti Bakrania, Head of Biologics Discovery and Development at LifeArc said:
“We’re really proud to have played a small but important part in discovering this promising new therapeutic antibody for Alzheimer’s disease and we look forward to hearing the regulator’s decision to allow patient access. It feels like a turning point for the amyloid hypothesis – and it reminds us that the translational work that we perform here may one day go on to deliver valuable benefits for patients.
“While these effects were small, they demonstrate a significant step forward in the long journey to find a treatment for Alzheimer’s disease – it is the first time that any treatment has shown a clinical benefit for people affected by this devastating condition. This is very encouraging news for both patients and their families, as well as researchers working on the beta-amyloid hypothesis.
“Unfortunately, this lengthy treatment regime was associated with some adverse side effects. Some patients may also be more susceptible to side effects than others so a tailored treatment approach may be needed. We hope this study will encourage more research and lead to more effective and safer treatments.
“Either way, this trial is a crucial moment which could ultimately become life changing for patients.”
On our involvement, Preeti says:
“It’s particularly pleasing to find out that the humanised antibody sequence that left our laboratory all those years ago is exactly the same as the version that’s now being tested in the clinic, which is a true testament to our expertise in this area. We’ve since collaborated with BioArctic on several other projects – demonstrating the confidence they have in our abilities to engineer therapeutic antibodies.”
LifeArc scientists have also worked on another humanised antibody treatment for Alzheimer’s called TAP01_04, which targets different, low molecular weight soluble forms of the amyloid beta protein. As the TAP01_04 antibody does not bind to plaques, it could potentially cause fewer side effects than lecanemab.
Work with us
Find out more about LifeArc’s antibody engineering capabilities – from initial generation to lead candidate – and ways of working with us.