FDA OKs Another Drug for Early Alzheimer’s Disease

— Decision provides patients a 2nd anti-amyloid remedy option

by Judy George, Deputy Managing Editor, MedPage At the moment July 2, 2024

The FDA authorized donanemab (Kisunla) for the remedy of adults with early symptomatic Alzheimer’s illness with confirmed amyloid pathology, the agency announced Tuesday. This contains Alzheimer’s patients with mild cognitive impairment and mild dementia.

The once-month-to-month remedy is the very top anti-amyloid agent with proof to give a boost to stopping therapy when amyloid plaques are eradicated, drugmaker Eli Lilly said.

The FDA’s decision provides early Alzheimer’s patients a 2nd anti-amyloid remedy option after the agency’s pudgy approval of lecanemab (This team) in 2023.

“This approval is emblematic of the unusual period of Alzheimer’s analysis where now we luxuriate in the first class of illness-editing remedy that will within the rupture be outmoded in aggregate with unusual therapies — primarily primarily based on the biology of rising older — that pay attention on the total underlying complexities of this illness,” said Howard Fillit, MD, of the Alzheimer’s Drug Discovery Basis in Contemporary York City, in a voice.

“This milestone will no longer very top catalyze the next period of therapies, nonetheless furthermore reframe how we enlighten treatments,” Fillit persevered. “It’s promising to investigate cross-check that some patients truly enter remission, where they function pudgy amyloid clearance with out a resurgence in huge plaque buildup for quite a lot of years to coach.”

The FDA decision comes decrease than a month after its advisory committee unanimously supported donanemab for early Alzheimer’s illness, after weighing its risks and advantages.

Donanemab used to be examined within the portion III TRAILBLAZER-ALZ 2 trial of 1,736 early Alzheimer’s patients. The drug met the trial’s fundamental endpoint of commerce from baseline within the Integrated Alzheimer’s Disease Ranking Scale, slowing decline relative to placebo (P<0.001).

The drug furthermore met a key secondary endpoint, displaying much less decline on the Scientific Dementia Ranking-Sum of Packing containers at 76 weeks (P<0.001). In TRAILBLAZER-ALZ 2, 17% of contributors executed remedy at 6 months, 47% at 300 and sixty five days, and 69% at 18 months, primarily primarily based on PET amyloid stages.

Be pleased diverse anti-amyloid remedy, donanemab’s security points centered around amyloid-linked imaging abnormalities (ARIA) with edema or effusion (ARIA-E) and ARIA with microhemorrhages and hemosiderin deposits (ARIA-H). Infusion-linked reactions and headache furthermore emerged after remedy.

In TRAILBLAZER-ALZ 2, 24% of donanemab-handled contributors had ARIA-E and 31.4% had ARIA-H. Two ARIA-linked deaths luxuriate in been attributed to donanemab. ARIA befell more continually in APOE4 homozygotes than heterozygotes or noncarriers.

The drug comes with a boxed warning for ARIA and says APOE4 checking out wants to be done earlier than initiating remedy. The warning cautions that serious intracerebral hemorrhages, including fatal hemorrhages, luxuriate in been seen with this class of medications. Because ARIA-E can motive focal neurologic deficits that could maybe maybe mimic ischemic stroke, clinicians must still place in options whether indicators would be attributable to ARIA-E earlier than giving thrombolytic therapy to patients handled with donanemab.

The boxed warning furthermore asks clinicians to handle in options the advantages of remedy and the possibility of ARIA when deciding to prescribe donanemab.

Dosing instructions uncover prescribers can place in options stopping remedy primarily primarily based on the elimination of amyloid plaques to minimal stages, as assessed on amyloid PET.