Aduhelm aducanumab Alzheimer's drug donanemab explainer donanemab lecanemab

CTAD: Lecanemab On Track to File for FDA Approval In Early 2023

By Simon Spichak, MSc | November 30th, 2022

UPDATE, 7 July 2023: Lecanemab has received full, traditional FDA approval and is available to patients under the brand name Leqembi.

Much anticipated Phase 3 data for Alzheimer’s drug lecanemab was presented at CTAD in 2022, showing the drug is as safe as the placebo with improvements in cognitive function.

Two months ago, Eisai and Biogen announced their Alzheimer’s anti-amyloid drug lecanemab appeared to be successful in slowing cognitive declineNow, the drugmakers have presented the much-awaited Phase 3 trial data at this year’s Clinical Trials on Dementia (CTAD) Congress, setting the stage for a decision from the FDA early next year. The findings were concurrently published in the New England Journal of Medicine

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.

Importantly, the drug outperformed Aduhelm in slowing cognitive decline and led to less adverse events.

(In February 2024, Biogen took Aduhelm off the market indefinitely.)

Despite widely publicized reports of two deaths associated with the clinical trial, there were no significant differences between deaths in the placebo and lecanemab groups.

“Based on the Clarity AD results, the investigational anti-amyloid beta protofibril antibody lecanemab has the potential to make a clinically meaningful difference for people living with the early stages of Alzheimer’s disease and their families by slowing cognitive and functional decline,” said Lynn Kramer, MD, chief clinical officer, Alzheimer’s Disease and brain health at Eisai Co.,

Despite widely publicized reports of two deaths associated
with the clinical trial
, there were no significant differences
between deaths in the placebo and lecanemab groups.

Ltd. The company plans to file for authorization of the drug in the U.S and Europe by the end of March 2023.  

What do the lecanemab trial 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.

As University of Pittsburgh School of Medicine Professor of Neurobiology Karl Herrup pointed out in a previous article, 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. 

Lecanemab also outperformed the placebo group across three other cognitive tests. There was also a significant decline in plaques within the lecanemab group but not the placebo.

Despite being more than aducanumab, some Alzheimer’s experts are also quick to note that this near half-point isn’t considered a major improvement. Rob Howard, professor of old age psychiatry at University College London Institute of Mental Health is among them.

“This is below what is considered the minimum clinically important difference of 1.0 point,” Howard wrote to Being Patient. “So, it isn’t clinically significant or noticeable in an individual patient.” He added that he does not believe the cognitive benefits outweigh the risks and was unconvinced by some of the analysis predicting patients’ response past 18 months. 

Serious adverse effects occurred in about one in seven people given lecanemab and one in nine in the placebo group. The majority of these effects occurred as a result of infusion-related reactions, swelling of the brain (commonly known as ARIA or ARIA-E).

One of the main criticisms leveled against Aduhelm and other Alzheimer’s clinical trials is a lack of diversity among the participants — the Centers for Medicare and Medicaid Services (CMS) even required Biogen and Eisai to run an additional trial with more diversity before considering covering the drug. This means that the sample used in the Aduhelm trial may not accurately reflect the population of patients who would later take it. 

The lecanemab trial made some improvements: about 5 percent of participants were Black and another 22.5 percent were Hispanic. Unlike other studies, the lecanemab trial also included patients that had other medical conditions like hypertension, diabetes, heart, and kidney disease. 

What is next for lecanemab and Alzheimer’s anti-amyloid drugs?

The FDA will assess the data from the clinical trials to determine whether the drug will be approved. If the drug is approved in 2023, it will be up to the CMS to decide whether or not they will provide insurance coverage for the drug or require an additional study.

Meanwhile, Biogen and Eisai will continue assessing patients who continue receiving the drug to map out whether the benefits continue past 18 months of treatment.

“These peer-reviewed, published results show lecanemab will provide patients more time to participate in daily life and live independently,” the Alzheimer’s Association said in a written statement. “It could mean many months more of recognizing their spouse, children and grandchildren.”

UPDATED 30 November 2022, 8:01 A.M. ET: Insights from an Alzheimer’s researcher at University College of London that were not received by the time of publication were added.

UPDATE: 3 March 2024, 8:30 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.

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