Lecanemab linked to slower rates of decline in early Alzheimer’s disease through 48 months

Key takeaways:

• Patients initially received placebo then used lecanemab from 18 through 48 months.
• Treatment outcomes were compared with comparator groups in ADNI and BioFINDER 1.
• Differences grew as time progressed.

Differences in outcomes between patients with early Alzheimer’s disease who were assigned lecanemab-irmb and matched controls increased through 48 months, according to data presented at the Alzheimer’s Disease International Conference.

“The Clarity AD core study and open-label extension now include more than 4 years of continuous lecanemab treatment,” Christopher H. van Dyck, MD, professor of psychiatry, neurology and neuroscience and director of the Alzheimer’s Disease Research Unit at Yale School of Medicine, said during his presentation.

Clarity AD included 1,795 patients with early AD (mean age, 71.3 years) randomly assigned 1:1 to biweekly IV infusions of 10 mg/kg lecanemab-irmb (Leqembi, Eisai) or placebo for 18 months.

“After the double-blind phase, we went into the extension phase,” van Dyck said.

Between 18 and 48 months, 1,412 patients received treatment with lecanemab-irmb. 

Christopher H. van Dyck

“There have been a few, just since April, who have transitioned to monthly infusions, consistent with the FDA approval of that regimen,” he said. “More significant, though, is the number who have transitioned to subcutaneous injections.”

Differences in adjusted mean changes from baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) between patients assigned lecanemab-irmb in Clarity AD and a comparator group from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) included 0.52 at 18 months, 1.01 at 36 months and 1.75 at 48 months.

Similarly, differences in adjusted mean changes from baseline in CDR-SB between patients assigned lecanemab-irmb in Clarity AD and a comparator group from the Swedish BioFINDER 1 study included 0.57 at 18 months, 1.4 at 36 months and 2.17 at 48 months.

The groups from the three studies were very similar in age and in APOE4 carrier status, van Dyk said, with particularly close matching between Clarity AD and ADNI in disease stage. The BioFINDER 1 patients all had mild cognitive impairment. 

“Introduction of the BioFINDER cohort adds further support for the notion that there’s continued benefit for lecanemab over time, over the full 4 years, in a disease-modifying pattern,” van Dyck said.

Risk of progression to the next stage of disease also fell by 34% at 48 months with lecanemab-irmb, compared with ADNI, he said. Proportions of patients who progressed to the next stage included 53.3% with lecanemab-irmb and 70.1% in ADNI.

“The results are more striking if still if we look specifically at progression to the dementia stage,” van Dyck said. “Now, there’s a 56% delay relative to ADNI at 48 months.”

Specifically, 18.6% of the lecanemab group and 37.4% of the ADNI group progressed to dementia based on a score of 9.5 to 15.5 for moderate dementia or 16 to 18 for severe dementia in CDR-SB. Patients assigned lecanemab-irmb also spent more time in earlier stages of disease than those who did not have treatment.

“At 18 months, the amount of decline by actively treated individuals has already been reached by placebo folks 5.7 months earlier,” van Dyck said.

Compared with the ADNI group, the lecanemab-irmb group had saved 5 months at 18 months and 10.7 months at 48 months. Compared with BioFINDER 1, the lecanemab group had saved 5.5 months at 18 months and 13.1 months at 48 months.

“With 4 years of treatment, we’re in the vicinity of a full year time saved,” van Dyck said.

Patients with the lowest pathology tended to have the best results, he said.

Among patients with low tau, 76% of those assigned lecanemab-irmb and 55% of those assigned to placebo had no decline at 48 months, whereas 69% of the full cohort — all on treatment — had no decline at 48 months. Also, 60% of those assigned lecanemab-irmb and 28% of those assigned to placebo had improved at 18 months, with 56% of the full cohort showing improvement at 48 months as well.

Rates of adverse events included 81.9% of the placebo group and 88.9% of the lecanemab group, both at 18 months, and 92.4% for the full cohort at 48 months. Rates of serious adverse events included 11.3% for the placebo group, 14% for the lecanemab group, again both at 18 months, and 22.8% for the full cohort at 48 months.

Overall, rates of adverse events fell from 83% at 12 months to 74% at 24 months, 69% at 36 months and 58% at 48 months. Rates for most events fell through 48 months, especially those related to amyloid-related imaging abnormalities (ARIA), with no rates going up.

Rates of ARIA-edema specifically fell from 13% at 12 months to 4% at 24 months and 1% at both 36 and 48 months.

“Most of these events occur in the first 6 months,” van Dyck said. “After that, really, the rates are at placebo levels.”

Based on these findings, van Dyck said treatment with lecanemab-irmb was associated with slower decline in early dementia and long-term safety, with no new safety signals.

“In Clarity AD, the observed increasing treatment difference with lecanemab treatment vs. matched controls in ADNI and BioFINDERS was consistent with a disease-modifying effect,” he said.

For more information:

Christopher van Dyck, MD, can be reached at neurology@healio.com.