Neurology > > Alzheimer’s Disease– Decision offers clients a 2nd anti-amyloid treatment alternative
by Judy George, Deputy Managing Editor, MedPage Today July 2, 2024
The FDA authorized donanemab (Kisunla) for the treatment of grownups with early symptomatic Alzheimer’s illness with validated amyloid pathology, the firm revealed Tuesday. This consists of Alzheimer’s clients with moderate cognitive problems and moderate dementia.
The once-monthly treatment is the only anti-amyloid representative with proof to support stopping treatment when amyloid plaques are eliminated, drugmaker Eli Lilly stated.
The FDA’s choice provides early Alzheimer’s clients a 2nd anti-amyloid treatment alternative after the company’s complete approval of lecanemab (Leqembi) in 2023.
“This approval is emblematic of the brand-new age of Alzheimer’s research study where we now have the very first class of disease-modifying drugs that will become utilized in mix with unique treatments– based upon the biology of aging– that target all the underlying intricacies of this illness,” stated Howard Fillit, MD, of the Alzheimer’s Drug Discovery Foundation in New York City, in a declaration.
“This turning point will not just catalyze the next generation of treatments, however likewise reframe how we provide treatments,” Fillit continued. “It’s guaranteeing to see that some clients basically get in remission, where they accomplish complete amyloid clearance without any renewal in considerable plaque accumulation for a number of years to follow.”
The FDA choice comes less than a month after its advisory committee all supported donanemab for early Alzheimer’s illness, after weighing its dangers and advantages.
Donanemab was checked in the stage III TRAILBLAZER-ALZ 2 trial of 1,736 early Alzheimer’s clients. The drug fulfilled the trial’s main endpoint of modification from standard in the Integrated Alzheimer’s Disease Rating Scale, slowing decrease relative to placebo (P< 0.001).
The drug likewise fulfilled an essential secondary endpoint, revealing less decrease on the Clinical Dementia Rating-Sum of Boxes at 76 weeks (P< 0.001). In TRAILBLAZER-ALZ 2, 17% of individuals finished treatment at 6 months, 47% at 12 months, and 69% at 18 months, based upon PET amyloid levels.
Like other anti-amyloid drugs, donanemab’s security concerns focused around amyloid-related imaging irregularities (ARIA) with edema or effusion (ARIA-E) and ARIA with microhemorrhages and hemosiderin deposits (ARIA-H). Infusion-related responses and headache likewise emerged after treatment.
In TRAILBLAZER-ALZ 2, 24% of donanemab-treated individuals had ARIA-E and 31.4% had ARIA-H. 2 ARIA-related deaths were credited to donanemab. ARIA happened more regularly in APOE4 homozygotes than heterozygotes or noncarriers.
The drug includes a boxed caution for ARIA and states APOE4 screening ought to be carried out before beginning treatment. The caution warns that severe intracerebral hemorrhages, consisting of deadly hemorrhages, have actually been seen with this class of medications. Due to the fact that ARIA-E can trigger focal neurologic deficits that can imitate ischemic stroke, clinicians ought to think about whether signs might be due to ARIA-E before offering thrombolytic treatment to clients treated with donanemab.
The boxed caution likewise asks clinicians to think about the advantages of treatment and the threat of ARIA when choosing to recommend donanemab.