Thoughts on the Lecanemab approval:
It turns out that, in this approval, Billy Dunn got around the Aduhelm SAB disapproval problem by not convening the SAB at all. Per a post on Linkedin by Subha Basu, "Lecanemab [was] approved by the FDA WITHOUT input from an advisory Committee." This detail was not reported in Feuerstein's STAT article (Surprise!), although I would think that is a newsworthy bit of information.
Maybe Billy Dunn isn't as desperate as I thought -- just one of the last true believers in the amyloid theory. Per the STAT article, Dunn is quoted as saying, "“This treatment option is the latest therapy to target and affect the underlying disease process of Alzheimer’s, instead of only treating the symptoms of the disease.” Easy for him to say, I guess, without that pesky Science Advisory Board to contradict him this time. Of course, Dunn may find that Leqembi, for all its incremental advantages over Aduhelm, will not now be greeted with open arms by Medicare, private insurers, the academic community, and European regulators. For what it's worth, Biogen's market cap went up a whole $1.1B today on the approval news,
Last and not least, there was a very interesting observation regarding APOE4++ patients treated with Lecanemab. Per STAT, "Some data from Eisai’s clinical trial suggested that approximately [the] 10% of people who carry two copies of APOE4, the most common genetic risk factor for Alzheimer’s, don’t benefit from Leqembi and may actually be harmed by it."
There are multiple things to note here. First, that APOE4++ status is problematic even for this amyloid-attacking AD drug. Does that mean that the APOE4++ induced plaques are different in kind than others? I suppose it's possible. But it may instead be that these patients are suffering from a disease variant that is so much more severe (and different in kind in some critical pathways), such that it fails to reduce its decline (at least relative to the broader AD universe) even with this symptomatic treatment. Patients might not be harmed by the treatment; it just may be that the APOE4++ patients decline so much faster that, even treated, they continue to look worse. Or not; it depends on information we yet don't have.
However, this observation with Leqembi reinforces my belief that we will see a similar ineffectiveness among the APOE4++ group in the blarcamesine trial. If Leqembi can't treat even the symptoms of the APOE4++ subset, isn't it at least as likely blarcamesine can't treat its cause? A symptomatic treatment should be more agnostic in this regard. Conversely, does this also imply that blarcamesine will do best with the ~ 30 percent of AD sufferers who are APOE4 negative? How did Leqembi do with that group?
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