AD/PD™️ 2024 – News Nugget – Improved amyloid clearance at 18 months with donanemab vs aducanumab

By Lucy Piper, medwireNews reporter

medwireNews: Superior lowering of amyloid plaque with donanemab compared with aducanumab in patients with early symptomatic Alzheimer’s disease (AD) extends to 18 months, show findings from the TRAILBLAZER-ALZ 4 trial.

These findings show further improvement on the enhanced amyloid lowering with donanemab previously reported at 6 and 12 months of treatment, “with no new safety signals emerging from the trial,” said presenter Stephen Salloway (Butler Hospital, Providence, Rhode Island, USA).

He reported at AD/PD 2024 in Lisbon, Portugal that amyloid plaque clearance, defined as less than 24.1 centiloids on positron emission tomography (PET) scans, was seen at 18 months in 77.5% of 56 patients receiving donanemab, compared with 42.5% of 58 assigned to receive aducanumab, a significant difference.

A similarly significant difference of 77.0% versus 34.5% was also seen among 25 donanemab-treated and 23 aducanumab-treated participants who had low-to-medium baseline levels of tau PET of between 1.10 and 1.46 standardized uptake value ratio (SUVr).

For the phase 3, open-label trial, patients were randomly assigned to receive either intravenous donanemab every 4 weeks at a dose of 700 mg for the first three doses followed by 1400 mg thereafter or aducanumab every 4 week at a dose of 1 mg/kg for the first two doses, increasing to 3 mg/kg for the next two doses, 6 mg/kg for the following two doses, and 10 mg/kg for subsequent doses.

The participants (57% women) were aged a mean of 73 years had a mean baseline amyloid level of 97–102 centiloids and a tau PET SUVr of 1.26–1.27.

Amyloid levels decreased from baseline by a least squares mean of 86.3 centiloids with donanemab treatment, which was significantly greater than the 72.8 centiloids achieved with aducanumab. For the low-to-medium tau subpopulation, the corresponding reductions were 84.6% and 71.0%, but the difference was not statistically significant.

Donanemab was not only associated with higher amyloid reductions than aducanumab, but also a faster rate of clearance, Salloway noted, with clearance achieved in a median of 359 days compared with 568 days with aducanumab.

Both treatments had a positive effect on plasma biomarkers at 18 months, as they did at 6 and 12 months. Specifically, phosphorylated (p)-tau decreased by 33.2% with donanemab and 25.7% with aducanumab, p-tau 181 by 18.0% versus 14.3%, and glial fibrillary acidic protein by 20.0% versus 13.7%.

Adverse events (AEs) occurred in 83.1% of individuals treated with donanemab and 87.0% of those treated with aducanumab. Amyloid-related imaging abnormalities (ARIA)–edema/effusions were the most common treatment-emergent AE, occurring in a respective 23.9% and 34.8% of patients. These events were primarily asymptomatic, although 1.4% of these events in the donanemab group and 2.9% in the aducanumab group were deemed serious. There were no deaths.

Salloway concluded that the data show that “with donanemab it is possible to achieve a more rapid amyloid lowering without a change in safety.” He added that given the rate of amyloid clearance with aducanumab was lower but the rate of ARIA higher, “the ARIA that is seen cannot be fully explained by amyloid lowering” and suggested that other components were at play.

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2024 Springer Healthcare Ltd, part of the Springer Nature Group

AD/PD 2024; Lisbon, Portugal: March 5–9