Regulatory authorities in the UK are being urged to speed their review of lecanemab (Leqembi, Eisai) after the US Food and Drug Administration (FDA) approved it for early-stage Alzheimer's disease.
The FDA move was widely welcomed by experts as a "step change" for treatment of Alzheimer's and a signal that drugs could alter the course of the disease.
Alzheimer's Research UK said concluding an urgent appraisal by the Medicines and Healthcare products Regulatory Agency (MHRA) and the National Institute for Health and Care Excellence (NICE) could "strengthen the UK's international reputation as a leader in dementia".
However, other experts highlighted that the clinical benefits of the drug may be "undetectable" in an individually treated patient. In addition, the NHS are said to lack the clinical infrastructure needed to facilitate treatment with the drug.
Positive Clinical Trial Results
Lecanemab became the first amyloid beta-directed monoclonal antibody for Alzheimer's treatment to be converted from accelerated approval to traditional approval after the FDA's advisory committee unanimously endorsed it as an effective treatment based on results of a post-marketing phase 3 study (CLARITY AD).
The immunotherapy drug works with the body's immune system to clear amyloid protein build-up from the brains of people living with early-stage Alzheimer's.
The US decision represents a "milestone in the search for effective therapies for Alzheimer's disease", Dr Nick Fox, director of the dementia research centre and professor of clinical neurology at University College London (UCL), told the Science Media Centre, and he "supports the widely held view in the field that this drug does deliver clinical benefit and slows disease progression".
Professor Tara Spires-Jones, president of the British Neuroscience Association, said the significance, apart from offering hope to patients, lies in providing "motivation for scientists and funders who now know in principle that the disease can be stopped".
"Not a Panacea"
Dr Adrian Ivinson, of the UK Dementia Research Institute, cautioned that lecanemab "is not a panacea" and that while it can slow the rate of decline from the disease, "it won’t repair the damaged brain or even halt the disease process".
Whilst results from the post-marketing trial submitted to the FDA suggested a 27% slowing of the disease course, "the benefits of lecanemab are so modest as to be undetectable in an individual treated patient", according to Robert Howard, professor of old age psychiatry at UCL, who stressed that regulators must also consider the drug's adverse effects, such as "brain swelling and bleeding" and "even death".
Hilary Evans, chief executive of Alzheimer’s Research UK believes scientists "can, and must, do better – both in terms of delivering drugs that are even more effective, with fewer side effects, and also treatments for people with later stage Alzheimer's and those with other forms of dementia".
Despite the drawbacks, many experts have dared to hope we are at the beginning of a new era for treating neurodegenerative diseases. "The approval of Lecanemab provides the proof that this is possible," said Bart De Strooper, professor of Alzheimer’s disease at the UK Dementia Research Institute.
NHS Has 'a Lot of Work to Do'
James Rowe, professor of cognitive neurology in the Department of Clinical Neurosciences at the University of Cambridge, urged the MHRA and NICE "to complete their reviews on lecanemab with the urgency that is felt by so many families".
However, he cautioned that there is a lot of work to do before lecanemab and similar drugs could be offered safely and equitably, including "better diagnosis, genotyping and issues that raises, improved MRI access, and the specialist NHS staff and sites to safely administer advanced therapies".
Alzheimer's Research UK noted that access to the drug requires that diagnosis be confirmed with a PET scan, but that the UK had one of the lowest numbers of scanners per capita in the developed world and without action to address the shortfall, access would be significantly limited.
Lecanemab does not currently have a marketing authorisation in the UK, although Eisai have applied for one to the MHRA. The Department of Health and Social Care asked NICE last December to carry out an appraisal of lecanemab, but the consultation is not due to begin until late August this year.
The regulatory bodies will need to be satisfied not only that lecanemab is safe and effective, but that it is cost-effective too, according to Dr Richard Oakley, associate director of research and innovation at the Alzheimer’s Society. For those reasons, he said, "there is still a long way to go before we see lecanemab available on the NHS".