THD NewsDesk, New Delhi: The research published in the NEW ENGLAND JOURNAL of MEDICINE on March 13, 2021 states that Donanemab is a humanized immunoglobulin G1 antibody specific for an N-terminal pyroglutamate amyloid-β epitope that is present only in mature brain amyloid plaques. As of now two phases have been tested yet, with Phase 2 trial which is a recent one:-
- In Phase 1, donanemab significantly reduced amyloid plaque, even with a single dose, in participants with amyloid-positive AD. For further evaluation, Dr Mark A. Mintun, M.D. and colleagues conducted a phase 2 study to assess the safety, tolerability and efficacy of donanemab
- In a recent Phase 2 trial, researchers have found that donanemab met its primary endpoint and showed significant slowing of decline on the integrated Alzheimer’s Disease Rating Scale (iADRS), a composite measure of cognition and daily function, in patients with early symptomatic Alzheimer’s disease (AD) compared to placebo. A hallmark of Alzheimer’s disease is the accumulation of amyloid-β (Aβ) peptide.
TRAILBLAZER-ALZ was a multicentric, randomized, double-blinded, placebo-control study of 257 patients with early symptomatic Alzheimer’s disease who had tau and amyloid deposition on positron-emission tomography (PET).
Researchers assessed the change in scores on the Clinical Dementia Rating Scale–Sum of Boxes (CDR-SB), the 13-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-Cog13), the Alzheimer’s Disease Cooperative Study–Instrumental Activities of Daily Living Inventory (ADCS-iADL), and the Mini-Mental State Examination (MMSE), as well as the change in the amyloid and tau burden on PET.
Researchers randomly assigned them to receive either donanemab (700 mg for the first three doses and 1400 mg thereafter) (n=131) or placebo (n=126) intravenously every 4weeks for up to 72 weeks. The major outcome assessed was the change from baseline in the score on the Integrated Alzheimer’s Disease Rating Scale (iADRS; range, 0 to 144, with lower scores indicating greater cognitive and functional impairment) at 76 weeks.
Its Key findings were:
- The baseline iADRS score was 106 in both groups.
- Researchers found a change from baseline in the iADRS score at 76 weeks which was 6.86 with donanemab and 10.06 with placebo (difference, 3.20).
- However, the results for most secondary outcomes showed no substantial difference.
- At 76 weeks, they noted reductions in the amyloid plaque level and the global tau load were 85.06 centiloids and 0.01 greater, respectively, with donanemab than with placebo.
- They also noted amyloid-related cerebral edema or effusions (mostly asymptomatic) with donanemab.
“In patients with early Alzheimer’s disease, donanemab resulted in a better composite score for cognition and for the ability to perform activities of daily living than placebo at 76 weeks, although results for secondary outcomes were mixed. Longer and larger trials are necessary to study the efficacy and safety of donanemab in Alzheimer’s disease”, concluded the authors.