Table 2.
Patient characteristics, and efficacy/safety outcomes of the trials.
| Sr. No. | Author, Year | Sample Size | Age (Years) | Gender (Female) | Severity of AD | APOE-ε4 Carriers | Efficacy | Safety |
|---|---|---|---|---|---|---|---|---|
| 1 | Lowe (2), 2021 | N = 63; Donanemab, n = 51; placebo, n = 12 | 69.7 ± 16.4 years | 33 (52.4%) | MCI/Mild: 40/51 (78.4%) patients who received Donanemab and 9/12 (75%) patients who received placebo; moderate: 5/51 (9.8%) patients who received Donanemab and 3/12 (25%) who received placebo | NR | Donanemab was well-tolerated up to 10 mg/kg; Single-dose administration from 0.1 to 3.0 mg/kg yielded a mean terminal elimination half-life of ~ 4 days and this increased to ~ 10 days at 10 mg/kg; only 10-mg/kg dosage showed changes in amyloid PET, with a mean SUVR change of −0.26 (SD: −0.26) and mean CL change of −44.4 (SD: 14.2); around 90% of subjects developed anti-drug antibodies at 3 months after a single dose | No deaths or drug-related serious adverse events were reported; 6 of 37 patients (16.2%) who received IV Donanemab had mild-to-moderate infusion reactions; two patients (3.9%) in the intervention arms had asymptomatic ARIA-microhemorrhage; four participants (6.4%) across the entire cohort had serious adverse events not related to study drug, including hip fracture, cervical vertebral fracture, urinary tract infection, and noncardiac chest pain |
| 2 | Lowe, 2021 | N = 61; Donanemab, n = 46; placebo, n = 15 | 73.2 ± 8.1 years | 34 (55.7%) | Mean (SD) MMSE score: 21.1 (4.0) | 47/61 (77.0%) patients; 11 homozygotes and 36 heterozygotes | Amyloid PET mean changes: at 24 weeks, from baseline for single doses were: −16.5 CL (SE = 11.22) with 10 mg/kg, −40.0 CL (SE = 11.23) with 20 mg/kg, and −49.6 CL (SE = 15.10) with 40 mg/kg; at 24 weeks, multiple dosage cohorts had −55.8 CL (SE = 9.51) with 10 mg/kg Q2w *, −50.2 CL (SE = 10.54) with 10 mg/kg Q4w, and −58.4 CL (SE = 9.66) with 20 mg/kg Q4w **; complete amyloid clearance (threshold of below 24.2 CL) established in 11 of 46 (23.9%) patients (one patient in the 20/mg single dose, one patient in the 40 mg/kg single dose, two patients in 10 mg/kg Q2w, two patients in 10 mg/kg Q4w, and five patients in 20 mg/kg Q4w); 45 out of 46 patients had positive TE-ADA with Donanemab | Seven serious adverse events in six patients (9.8%) were reported across the entire cohort (one patient died due to non-treatmen-related myocardial infarction, one had intermittent symptomatic cerebral edema (ARIA-E), and four patients had non-treatment-related events; 12 of 46 intervened patients (26.1%) developed vasogenic edema (ARIA-E) in all dosing regimens but the 10 mg/kg single-dose arm; 10 of 46 patients (21.7%) had microhemorrhage events (ARIA-H) across all dosing arms; 2 of 46 (4.4%) patients had superficial siderosis (ARIA-H) in the 10 and 20 mg/kg Q4w arms; 2 of 46 patients (4.4%) in the 20 mg/kg Q4w arm discontinued Donanemab due to TRAE |
| 3 | Mintun, 2021 | N = 272; Donanemab, n = 131; placebo, n = 126 | 75.2 ± 5.5 years | 145 (53.3%) | Mean (SD) MMSE score: 23.5 ± 3.1 (13.0–30.0) |
197/270 (73.0%) patients; 141 heterozygotes and 56 homozygotes | Difference between the Donanemab and placebo groups in the change from baseline at 76 weeks for iADRS was 32% (p = 0.04) in favor of Donanemab, calculated through the following scores: a reduction of 6.86 from 106.2 baseline iADRS scores in the intervention group and 10.06 reduction from a baseline score of 105.9; difference between the Donanemab and placebo groups in change from baseline to 76 weeks were −0.36 for the CDR-SB score, −1.86 for the ADAS-Cog13 score, 1.21 for the ADCS-iADL score, and 0.64 for the MMSE score; there was an 84.13 CL reduction in the Donanemab group on Florbetapir PET from baseline scores of 108 CL; amyloid negative status (amyloid plaque level of < 24.10 CL) was found in 52 (40.0%) patients, 78 (59.8%) patients, and 89 (67.8%) patients at 24, 52, and 76 weeks; there was no change in global tau load from baseline to 76 weeks as assessed by flortaucipir PET; at 52 and 76 weeks, there was a greater decrease in whole-brain volume and greater increase in ventricular volume in the Donanemab group vs. the placebo group | No significant difference between the Donanemab group and the placebo group in the incidence of death or serious adverse events; 119 of 131 participants (90.8%) in the Donanemab group and 113 of 125 participants (90.4%) in the placebo group had at least one adverse event; 35 of 131 (26.7%) participants developed an ARIA-E in the Donanemab group of whom 8 (6.1%) participants were symptomatic and 1 of 125 (0.8%) participants developed an ARIA-E in the placebo group; 40 of 131 (30.5%) participants had an ARIA-H event in the Donanemab group and 9 of 125 (7.2%) participants had an ARIA-H event in the placebo group; cerebral microhemorrage was present in 10 of 131 participants (7.6%) and 3 of 125 participants (2.4%) in the Donanemab and placebo group, respectively; superficial siderosis was present in 18 of 131 (13.7%) participants in the Donanemab group and 4 of 125 (3.2%) participants in the placebo group; infusion-related reaction was present in 10 of 131 (7.6%) participants in the Donanemab group and did not occur in the placebo group |
| 4 | Shcherbinin, 2022 | N = 272; Donanemab, n = 131; placebo, n = 126; combination, n = 15 | 75.2 ± 5.5 years | 145 (53.3%) | Same as Mintun (2021) | Same as Mintun (2021) | 46 of 115 (40%) of Donanemab participants reached a complete amyloid clearance threshold of 24.1 CL (r: –0.54), placebo-treated participants did have changed amyloid clearance change appreciably (r: –0.194); achieved amyloid clearance was sustained with a mean rate of reaccumulation of 0.02 CL (SD: 7.75) over a 1-year period; those who achieved an amyloid level ≤ 11 CL at week 24 would require a mean time of 3.9 years [95% CI: 1.9–8.3 years] to regain amyloid plaque levels above the threshold (>24.1 CL); a 34% slowing of overall tau level, measured using SUVR, was observed for Donanemab compared to placebo in the entire cohort at 76 weeks | All-cause mortality was lower in Donanemab-intervened participants (n = 1, 0.76%) compared to placebo (n = 2, 1.6%); no differences were reported in serious adverse effects among Donanemab (n = 26, 19.85%) and placebo (n = 25, 20%) groups |
* Q2: Every 2 weeks. ** Q4: Every 4 weeks. Acronyms: AD: Alzheimer’s disease; ADAS-Cog13: the 13-item cognitive subscale of the Alzheimer’s Disease Assessment Scale; ADCS-iADL: the Alzheimer’s Disease Cooperative Study–Instrumental Activities of Daily Living Inventory; ARIA: Amyloid-related imaging abnormalities; ARIA-E: Amyloid-related abnormalities due to cerebral edema; ARIA-H: Amyloid-related imaging abnormalities due to hemosiderin deposition and hemorrhage; CDR-SB: Clinical Dementia Rating Scale–Sum of Boxes; CL: Centiloids; iADRS: Integrated Alzheimer’s Disease Rating Scale; MCI: Mild cognitive impairment; MMSE: Mini-mental state examination; PET: Positron emission tomography; SD: standard deviation; SE: Standard error; SUVR: Standardized uptake value ratio; TE-ADA: Treatment-emergent anti-Donanemab antibodies; TRAE: Treatment-related adverse events.