On 27th September 2022, Eisai and Biogen published a press release with results from their Phase 3 trial of an anti-amyloid antibody lecanemab. The drug slowed decline on the primary outcome, a global measure of cognition and function called the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) with scores ranging from 0-18.
On the CDR-SB lecanemab was superior to placebo over 18 months by 0.45 points. This was heralded as a 27 percent reduction in decline over 18 months in the primary clinical outcome; there were smaller declines in secondary clinical endpoints.
The response to this announcement has been mixed. On one hand many commentators have questioned the clinical significance of such a small reduction. They are reserving judgement until they see the data.
On the other hand, the companies and those supporting the amyloid hypothesis for Alzheimer’s were excited as this is the first drug to demonstrate a benefit on a primary outcome in a randomised controlled trial for early Alzheimer’s disease.
Side effects occurred. The incidence of the brain swelling or oedema known as ARIA-E and microhaemorrhages was 12.5 percent, about one-third of that seen with Biogen’s approved anti-amyloid antibody aducanumab (also known as Aduhelm) which was approved controversially by the Food and Drug Administration in the United States (US) in June 2021.
Where to from here?
More results may be released at a conference in early December in the US. It is likely that the companies will make application to the FDA in the US, a process which will take some time. The outcome will depend on the details of the data. However, based on the accelerated approval awarded for aducanumab, the FDA may well give approval.
Other considerations are costs, not yet discussed, and administration. In the trial the drug was administered intravenously by intravenous infusion every two weeks. It is not clear for how long the drug will need to be given.
In Australia, the Therapeutic Goods Administration (TGA) is more cautious and FDA approval for lecanemab does not mean TGA will follow. Whether the US or Australia approves subsidised medication is even less certain. For now, watch this space.
In other news…
On 14th November 2022, Roche and Genentech announced negative top-line results for their anti-amyloid antibody, gantenerumab. The drug failed to slow cognitive decline on the CDR-SB. More results for lecanemab and gantenerumab are set to be released at a major conference in early December.
NOTE: Since this article was written, an article was published in the New England Journal of Medicine with more detailed results of the Phase 3 trial of Lecanemab.
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