New Alzheimer’s drug released

The big news this month is that Eisai’s drug lecanemab has been approved for release by the FDA (Federal Drug and Food Agency) under its secondary ‘accelerated approval’ pathway. Marketed as Leqembi, the drug moderately slowed cognitive decline in participants in clinical trials and is the first new treatment for Alzheimer’s in 20 years. It comes with concerns about adverse side effects, including brain bleeds and swelling, and there have been three related deaths. But with no real medical progress in Alzheimer’s for decades Leqembi is being hailed as a breakthrough. ‘This drug is not a cure,’ said Dr Joy Snider, a neurologist at Washington University in St. Louis. ‘it might mean someone could have an extra six months to a year of being able to drive.’

Leqembi is being marketed by long term partners Eisai and Biogen, and comes with a price tag of $26,000 per person. There will be additional medical costs, for example, a brain scan to determine the presence of amyloid plaques before beginning treatment then three additional brain scans during the first 14 weeks of treatment as a precautionary step to monitor for potentially serious brain swelling or bleeding episodes. Some commentators note that for Biogen, the new drug is an opportunity to reverse a decline in its business and repair its reputation after the failed launch of its similar drug, Aduhelm, following a Machiavellian FDA approval process that was lambasted Biogen for trying to maximize its profits at the expense of taxpapers and Alzheimer’s patients.

People who took part in the lecanemab trial had mild cognitive impairment, or early stage Alzheimer’s disease. Details of Eisai’s trial have been published in the NEJM (New England Journal of Medicine) and showed that lecanemab reduced markers of amyloid in early Alzheimer’s disease and resulted in moderately less decline on measures of cognition and function than placebo at 18 months but was associated with adverse events. Longer trials are warranted to determine its efficacy and safety in early Alzheimer’s disease. 12.6 percent of those taking lecanemab experienced brain swelling, compared with just 1.7 percent of those in the placebo group.

Leqembi’s labelling includes the trial’s narrow profile of people with early signs of dementia or mild cognitive impairment, and advises physicians to take ‘additional caution’ when considering its use in people who are also prescribed anti-blood clotting medication. Professor Luca Giliberto, a neurologist at Northwell Health’s Feinstein Institutes for Medical Research, New York, said the Institute will not prescribe for patients with these conditions, but thinks there is a subset of patients that will benefit from the drug. He said, ‘the effect sizes are minimal and may not be perceptible to patients or caregivers over the eighteen months shown in the trial but if you continue treatment long enough, two years or more, maybe the difference will improve.’

Eisai is funding several programs to educate and train physicians about the diagnosis and treatment of the side-effects. Leqembi will be available to physicians from the week of January 16, Eisai said, though its initial goal is not to ramp up sales in the initial phase, but to get the healthcare system ready.

The FDA approval of Leqembi has been hailed by Alzheimer’s Research UK as an ‘important milestone.’ Hilary Evans, chief executive of Alzheimer’s Research UK, said, ‘we know today’s news may prompt mixed emotions. There is still some way to go before lecanemab might reach patients in the UK. This period of uncertainty, while we wait for the UK regulator to conduct its own review, may be difficult for individuals with Alzheimer’s and their loved ones.’

Perhaps the Alzheimer’s Society should make clear in its literature that ‘effect sizes are minimal’, and that there are side-effects to be considered. It’s a “really tiny and almost unnoticeable difference from placebo”, says Rob Howard, a psychiatrist at University College London.

No one is hailing Leqembi as the ultimate cure for Alzheimer’s, rather, there’s a ‘wait and see what happens over time in the real world’ approach. Also, people with mild cognitive impairment would be reassured to know that it is not necessarily a precursor to Alzheimer’s. A report by the Mayo Clinic showed that it is reversible in 70 percent of cases.

Elderly with high cognitive levels but brains full of plaques.

And there continue to be studies showing that people are living with multiple protein deposits in their brains, without a trace of Alzheimer’s. Proponents of the amyloid B hypothesis say this is simply because their brains haven’t developed it yet.

But a study published just last month by the Alzheimer’s Association showed unequivocally that cognitively healthy elderly have Alzheimer’s neuropathology levels similar to Alzheimers patients – that is, their brains are brimming with plaque deposits. In addition, Alzheimer’s neuropathology loads do not correlate with cognitive performance in centenarians, and that some centenarians are resilient to the highest levels of Alzheimer’s neuropathology. But there seems to be no research into the reasons why these, in the study, and others are not affected. If their ‘secret’ could be discovered and harnessed, that would be a real breakthrough.

Although there’s great delight at the Leqemi approval, there are concerns that other research approaches are being stifled by the continuing emphasis on the amyloid B and tau deposits being the cause of Alzheimer’s.

The best approach is to follow the advice on how to avoid Alzheimer’s and dementia of all types. You only have to Google ‘how to avoid dementia’ and up come 193 million results in 66 seconds.