Pharmaceutical companies Eisai and Biogen have announced the first results from a Phase 3 human trial testing a drug designed to treat symptoms of dementia associated with Alzheimer’s disease. The drug seems to be successful at slowing cognitive decline, making it the first drug to ever effectively treat Alzheimer’s symptoms. However, experts are cautious in their optimism, suggesting more information is needed to understand exactly how meaningful this treatment will be for patients in the real world.
Lecanemab is an experimental monoclonal antibody designed to break down clumps of toxic proteins in the brain thought to be responsible for the neurodegeneration associated with Alzheimer’s disease. The antibodies bind to amyloid beta protein aggregations, interfering with their formation, and in some cases breaking down pre-existing accumulations.
A Phase 3 trial testing lecanemab recruited just under 2,000 participants in the early stages of Alzheimer’s disease with only mild cognitive impairment. Half were given fortnightly lecanemab infusions for 18 months, while the other half were given placebo infusions.
The primary goal of the trial was to evaluate each participant's rate of cognitive decline using a measure called CDR-SB (Clinical Dementia Rating-Sum of Boxes). This measure is a numeric scale designed to quantify the severity of dementia. Trained healthcare professionals interview Alzheimer’s patients and their caregivers, generating numerical scores across six cognitive areas.
At the end of the 18-month trial those in the lecanemab group showed signs of slower cognitive decline compared to placebo. From baseline, the rate of cognitive decline as measured by CDR-SB was 27% slower in the lecanemab group.
In a press release announcing the findings, Eisai and Biogen describe the results as “highly statistically significant.” And, from a trial perspective, these results are certainly significant, but Alzheimer’s experts are cautious in pointing out it’s unclear what this kind of slowing of cognitive decline actually means in the real world.
Rob Howard, from University College London, said these findings are certainly “an historic moment” in that they are the first clinical trial evidence of a drug slowing the symptomatic progression of Alzheimer’s. But whether the degree of efficacy cited in the trial is actually meaningful for patients is yet to be shown, and Howard indicates the scores cited in the trial are borderline in terms of worthwhile effect.
“Having shown efficacy, the next question is whether there is clinical effectiveness,” explained Howard. “A 0.45 point advantage on an 18-point scale, where the accepted minimum worthwhile difference ranges from 0.5 to 1.0 points, will mean that there are going to be some very difficult conversations and decisions in the next weeks and months.”
Hopefully some clarity will be offered when a full data readout from the trial is offered later in the year. This could shed some light on exactly how impactful this treatment may be on a patient with Alzheimer’s.
Tara Spires-Jones from the University of Edinburgh, said if the drug can extend a patient’s quality of life, even slightly, then it would be hugely meaningful to many patients.
“While this is not a 'cure' in that it doesn’t bring people back to normal, slowing cognitive decline and preserving the ability to perform normal daily activities would still be a huge win because people could live well for longer with Alzheimer’s disease,” said Spires-Jones. “If these data stand up to peer review, the drug could make a big difference and will be a fantastic example of how fundamental research into the brain can make people’s lives better.”
From a broader scientific standpoint the success of lecanemab bolsters the much-maligned amyloid hypothesis. After years of failed clinical trials testing anti-amyloid drugs, lecanemab somewhat proves targeting this particular protein can potentially slow Alzheimer’s symptoms.
“This is a very encouraging result for the Alzheimer’s research community, demonstrating that we are moving in the right direction by targeting clearance of the amyloid beta protein,” said Bart De Strooper, from the UK Dementia Research Institute. “There is real momentum in the field and several exciting trial results on the horizon in the coming year.”
If anything, this new lecanemab data does suggest effectively targeting amyloid aggregations in the early stages of Alzheimer’s could be a useful treatment. But lots of questions now arise as to exactly how this new drug can be incorporated into clinical contexts.
A drug needing fortnightly infusions is not going to be cheap or easy to administer en masse. Eisai and Biogen are currently in early phase trials for a subcutaneous version of the drug, meaning patients could more simply self-administer injections at home.
Tom Russ, director of Alzheimer Scotland Dementia Research Center, is looking forward to seeing more data but affirms this finding should give hope to dementia patients. He also noted health services should begin preparing for how this treatment can be equitably distributed if it does go on to be approved.
“The prospect of a disease-modifying drug for Alzheimer’s disease is an exciting one, which could improve many lives.” said Russ. “However, health services need to start thinking now how such drugs could be provided fairly, allowing everyone areas equal access to new treatments whether they live in remote, rural, or economically deprived areas.”
Source: Biogen
