Drugmakers Eisai and Biogen just announced the success of their latest Phase 3 trial for the Alzheimer’s anti-amyloid drug lecanemab, setting the stage for a decision from the FDA early next year.
When Aduhelm received approval from the FDA, it was met with a negativity — the clinical trials were far from conclusive, experts said, and the FDA’s own advisors recommended against the drug’s approval. The idea that Alzheimer’s is caused by the buildup of beta-amyloid plaques in the brain, and that clearing these plaques could slow the course of the disease, has been a leading theory for decades — but the drama around Aduhelm has made it more controversial than ever before. (In February 2024, Biogen took Aduhelm off the market indefinitely.) Amid the turmoil, the manufacturers Eisa and Biogen scaled down the production of the drug, shifting their efforts on another beta-amyloid targeting drug still in the pipeline: lecanemab.
On September 27th, Eisai and Biogen announced that their Phase 3 trial for lecanemab was successful in slowing cognitive decline. The drug was tested in a group of 1,795 people with mild cognitive impairment or mild Alzheimer’s. Compared to placebo, 18 months of biweekly lecanemab infusions led to a significantly lower rate of cognitive decline, according to the trial data.
The data will be presented in detail on November 29th at the Clinical Trials on Dementia Congress, then submitted for publication in a medical journal. The company plans to file for authorization of the drug in the U.S., Japan and Europe by the end of March 2023.
“Today’s announcement gives patients and their families hope that lecanemab, if approved, can potentially slow the progression of Alzheimer’s disease, and provide a clinically meaningful impact on cognition and function,” said Michel Vounatsos, chief executive officer at Biogen. “Importantly, the study shows that removal of aggregated amyloid beta in the brain is associated with a slowing of disease in patients at the early stage of the disease.
Penn Memory Center co-director Jason Karlawish hopes that the announcement marks a pivotal milestone in Alzheimer’s disease history, but clarifies that his hope is based on a press release.
“Science relies on the open and unbiased exchange of information, and three key means to achieve this are publishing results in a peer-reviewed journal, presenting the results to open scientific forums with ample time for discussion and debate, and making the data available for confirmatory analyses,” Karlawish said in an email to Being Patient. “I look forward to these events.”
What do the positive results mean for Alzheimer’s treatments?
The study used a measure of global cognition called the Clinical Dementia Rating Scale Sum of Boxes Score to track the trajectory of cognitive decline, scoring cognition from 0 to 18. A higher score is indicative of more cognitive impairment. For example, a score of 3 to 4 indicates very mild dementia while further cognitive decline bumps the score to 4.5 which is indicative of mild dementia.
Patients randomized to lecanemab appeared to have their rate of cognitive decline decreased by nearly half a point (0.45) compared to those in the placebo group.
That said, 0.45 is a relatively small change on the scale.
As University of Pittsburgh School of Medicine Professor of Neurobiology Karl Herrup points out, this isn’t too far from previous trials for Aduhelm (which was then being referred to by its generic name aducanumab), one of which found a difference of 0.39 points on the same scale and another which failed to show any differences.
“Any positive news in our field is good news,” Herrup wrote to Being Patient in an email. “That said, my early response (based on minimal and probably inadequate information) is that it would appear that the effect size is once again pretty small. Larger than aducanumab, but not much. So, it’s hard to take the announcement as a major victory.”
In a substantial improvement over Aduhelm (aducanumab), however, lecanemab’s early data is showing that the drug is half as likely as its predecessor to cause brain swelling, known as amyloid-related imaging abnormalities-edema/effusion (ARIA-E).
“The adverse events (ARIAs) are still with us,” Herrup noted, “and while it appears that most of these were asymptomatic I remain cautious since we do not know the longer term consequences.”
Lecanemab was also tested in a much more diverse population. About 25 percent Americans recruited for the study were either Black or Hispanic, compared to 3.6 percent in the Phase 3 trial for Aduhelm (aducanumab).
If lecanemab gets approval, does that mean it will be accessible to the people who need it?
The Centers for Medicare and Medicaid Services previously laid out a restrictive framework for extending Medicare coverage for all future anti-amyloid Alzheimer’s drugs after Aduhelm. Time will tell whether the 0.45-point margin of reduced cognitive decline will pass their standards for coverage.
“The companies described their test results as highly statistically significant,” Jim Taylor, President of Voice of Alzheimer’s, said in a news release. “They are also politically significant. Based on these results, we will demand that the federal government change its unfair policies on coverage of Alzheimer’s treatments.”
Terrie Montgomery, a founding board member of Voices of Alzheimer’s who is living with early-onset Alzheimer’s, added: “The Alzheimer’s community has been praying for a successful result and our prayers have been answered,” Montgomery said. “We will now turn our attention to our elected leaders and demand that lecanemab and similar treatments, once approved by the FDA, be covered by Medicare and Medicaid to make them accessible to the people who need them.”
Herrup is also looking ahead to this question of accessibility and insurance coverage.
“From a public health point of view, we still don’t know how lecanemab will be priced. so accessibility is an issue,” Herrup said. “My concerns remain that if widely adopted at the price points Biogen tried to establish for Aduhelm, it will rapidly bankrupt our healthcare system for only a modest benefit. The bottom line is that we need much more data.”
UPDATED: 28 Sept. 2022, 12:44 p.m. ET – This article was updated to include comments from a third-party subject matter expert which were received after publication.
UPDATED: 28 Sept. 2022, 4:07 p.m. ET – This article was updated to include comments from Voices of Alzheimer’s board members, who shared a press release after publication, and from Penn Memory Center’s Jason Karlawish, who emailed after publication.
UPDATE: 3 March 2024, 9:04 P.M. ET. In February 2024, Biogen took Aduhelm off the market, citing financial concerns. Although the drug did receive accelerated, conditional FDA approval for the treatment of early Alzheimer’s disease in 2021, it is no longer available to new patients. The company announced it would sunset trials in May 2024 and cease supplying the drug to current patients in November 2024.
