New Alzheimer’s Drug OK This Week Won’t Do Much for Patients: Article

As FDA prepares to render an accelerated approval decision this week on an Eisai and Biogen BLA for lecanemab (BAN2401), an investigational anti-amyloid beta protofibril antibody for treating Alzheimer’s disease, health/medicine journalist Joanne Silberner reminds readers in a 1/4 The Free Press article about how little progress has been made in Alzheimer’s research as much of the focus continues to be on reducing brain amyloid levels. The article leads one to wonder again whether other treatment approaches should be studied more aggressively.

“The goal of mitigating amyloid in the brain has held a vise-like grip on Alzheimer’s research for decades, despite the fact that, one by one, the drugs designed to address amyloid—around twenty of them— have shown virtually no beneficial effects on patients,” notes Silberner in her article.

With lecanemab, reported trial data showed the drug slowed cognitive decline among patients by 0.45 points on an 18-point scale. “You read that right — less than a one-point improvement in evaluations of patients’ memory, judgment, ability to care for themselves, and other measures,” she points out. “And that’s a slowing of deterioration, not a reversal.”

Silberner quotes University College London geriatric psychiatrist Rob Howard in The BMJ as saying lecanemab’s results show “just too small a difference to be noticed in an individual patient, and none of the reported results … reached accepted levels of improvement to constitute a clinically meaningful effect.” But he, and others, did note that the slowing of degeneration gave credence to the amyloid hypothesis — Howard called it “a believable path.” 

Silberner’s article also quotes anti-amyloid neuroscientist and former NIH researcher Daniel Alkon, who opined about patients who took lecanemab: “They are still declining. That’s not what we should be aiming for. After 20 years of failed trials, I think it’s reasonable to argue that it’s time to try to find a therapeutic approach that makes patients better rather than just slowing down the progression.”

The lecanemab accelerated approval decision, which is expected by the 1/6 user fee review action target date, comes on the heels of a recent Congressional report on FDA’s 2021 controversial review and approval of Biogen’s Alzheimer’s drug Aduhelm (see story). The report was sharply critical of the agency’s decision to work so closely with the company to guide the drug’s review and approval. It also took issue with Biogen setting an “an unjustifiably high price” despite a lack of demonstrated clinical benefit in a broad patient population.

If granted accelerated approval, the companies say they are planning next to seek lecanemab’s traditional approval by 3/31 based on recently reported Phase 3 confirmatory data, which suggest treated patients with early Alzheimer’s disease had reduced brain amyloid levels and moderately less decline on clinical measures of cognition and function than patients on placebo at 18 months, but they also experienced more serious adverse events than those on placebo. Specifically, they reported that lecanemab treatment reduced clinical decline by 27% on the global cognitive and functional scale, compared with placebo, and it “showed statistically significant reduction in amyloid plaque burden at all timepoints starting at three months.”