Meeting Coverage
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CTAD
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Different regimen showed comparable pharmacokinetic and pharmacodynamic results
by
Judy George, Deputy Managing Editor, MedPage Today
October 29, 2024
An alternate dosing plan for the anti-amyloid drug donanemab (Kisunla) reduced the risk of brain edema and effusion but still maintained sufficient amyloid reduction in early Alzheimer’s disease, the phase IIIb TRAILBLAZER-ALZ 6 study showed.
At week 24, the frequency of amyloid-related imaging abnormalities with edema and effusion (ARIA-E) was 23.7% for the standard dosing arm, and 18.6%, 18.3%, and 13.7% for each of three alternative dosing arms, reported John Sims, MD, of drugmaker Eli Lilly in Indianapolis, at the annual Clinical Trials on Alzheimer’s Disease meeting.
The standard dosing regimen was 700 mg of donanemab for the first three infusions, then 1,400 mg for each infusion after that. The modified titration arm with the lowest ARIA-E frequency (13.7%) was 350 mg for the first infusion, 700 mg for the second infusion, 1,050 mg for the third infusion, and 1,400 mg for each infusion after that.
The posterior probability of the modified titration arm achieving at least a 20% relative risk reduction in ARIA-E versus the standard arm was 94.1%.
“We were able to demonstrate that one of the dosing paradigms — the modified titration arm — did achieve success in lowering ARIA-E rates,” Sims said. “That was accompanied by lower symptomatic frequencies, lower radiographic severities, and a fairly dramatic impact on the [APOE4] homozygous population.”
The modified titration and standard dosing regimens had comparable pharmacokinetic profiles and a comparable pharmacodynamic effect on amyloid and plasma p-tau217, he added.
TRAILBLAZER-ALZ 6 is still ongoing but “given the clinical implications and the safety findings of this, we plan to submit and discuss this with global regulators for a possible update to labels,” Sims said.
Donanemab was approved by the FDA in July to treat adults with early symptomatic Alzheimer’s disease with confirmed amyloid pathology. The agency’s decision was based on results of the phase III TRAILBLAZER-ALZ 2 trial, in which donanemab slowed clinical progression relative to placebo (P
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