This article was first published in NeurologyLive.
Donanemab may provide better compositional scores for psychology and ability to perform activities of daily living after 76 weeks compared to placebo in patients with early-onset Alzheimer’s disease, according to new data from the phase 2 TRAILBLAZER study -ALZ, published in the New England Journal of Medicine and presented at AD / PD 2021.
The main outcome was the change from baseline in the score on the Integrated Alzheimer’s Disease Assessment Scale (iADRS), which ranged from 0–144, with lower scores indicating greater impairment of conscience and function. At baseline, iADRS score was 106 in both the donanemab (n = 131) and placebo groups (n = 126; 1 excluded from the modified-resolution groups).
After 76 weeks, treatment group scores changed by 6.6.86 points while placebo groups changed by −10.06 (difference, 3.20; 95% CI, 0.12–6.27; P. = .04). This change equated to a 32% difference in slow decline for the donanemab group, a large difference that was easily recognizable by month 9.
“We are confident in the results of the TRAILBLAZER-ALZ study,” Daniel Skovronsky, MD, PhD, chief scientific officer, and president, Lilly Research Laboratories, Eli Lilly and co., Head of donanemab, said in a statement. “This is the first late study in Alzheimer’s disease to meet the key point of the main study. Donanemab has the potential to be a very important treatment for Alzheimer’s disease.
“We were pleased to see not only a cognitive decline and slowing action, but also a massive eradication of amyloid pests and slowing the spread of tau pathology,” Skovronsky said. “Constellation of clinical results and biomarker Demonstrate the potential for long-term disease change. We are grateful to the patients, carers and researchers who took part in this special study. “
At the 76-week mark, reductions in amyloid plaque level were 85.06 centiloids (−84.13 vs. 0.93) greater with donanemab than with placebo.
Cerebral edema or amyloid-associated hemorrhage (ARIA-E), which was largely asymptomatic, occurs with donanemab treatment. As early as 6 months, 40% of those treated with donanemab achieved amyloid negativity (defined as an amyloid plaque level of <24.10 centiloids), with 68% achieving this at 18 months. The percentage of participants in the donanemab group who had amyloid-negative status was 24, 52, and 76 weeks at 40.0%, 59.8%, and 67.8%, respectively.
“The combination of changes in Alzheimer’s biomarkers and slowing of clinical manifestations of the disease seen in this study is promising,” said Howard Fillit, MD, founding executive director and chief science officer, Alzheimer’s Drug Discovery Foundation (ADDF), in the report on the data. ”We are encouraged by today’s news, and if these results are confirmed in the larger ongoing study, donanemab could provide the potential past for disease modification treatment that will help patients with mental abilities and maintain their independence longer. We are eagerly awaiting results from future trials. ”
In the safety population, 90.8% (n = 119) of the donanemab group and 90.4% (113 of 125) of the placebo group had at least 1 adverse effect (AE) in the double-blind intervention period. The incidence of ARIA-E was significantly higher in the donanemab group (26.7%) than in the placebo group (0.8%; P. <.001). Symbolic ARIA-E was reported by 6.1% of participants in the donanemab group (22% of those with ARIA-E), compared with 0.8% of participants in the placebo group.
The majority of cases of ARIA-E occurred at or before week 12 of the intervention period, with the very typical cases (n = 2; 1.5%) occurring in the donanemab group. The symptoms resolved in these two patients, in an average time of 18 weeks.
The results for the secondary test results were mixed. These measures included a change in scores on the Clinical Dementia Assessment Scale – Box Sum (CDR-SB), the 13-scale cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-Cog13), Collaborative Study Alzheimer’s Disease – Daily Inventory Instrumentation Activity (ADCS-iADL), and the Mini-Mental State Examination (MMSE), as well as the change in the amyloid load and tau on positron emission tomography (PET).
The difference between the donanemab group and the placebo group in the change from baseline at 76 weeks was −0.36 (95% CI, −0.83 to 0.12) for a CDR-SB score, −1.86 (95%). CI, −3.63 to −0.09) for ADAS-Cog13 score, 1.21 (95% CI, −0.77 to 3.20) for ADCS-iADL score, and 0.64 (95% CI, −0.40 to 1.67) for MMSE score.
Lead author Mark A. Mintun, MD, vice president, Pain and Neurodegeneration Research and Clinical Development, Eli Lilly and Company; the president, Avid Radiopharmaceuticals, and colleagues noted that several aspects of the design of the trial were worth considering, including the choice of the dosing regimen (700 mg for the first 3 doses, 1400 mg afterwards) taken to aid in the aggressive removal of amyloid plaques.
In addition, all participants were asked to meet the PET flortaucipir screening criteria, which may “have reduced the range of underlying pathologic features and, consequently, reduced shrinkage. clinical ”as well as those with the highest levels of tau should be prohibited.
As the lawsuit followed Baysien’s disease progression model proposed by the European Alzheimer’s Dementia Prevention project, Mintun et al noted that it yielded estimates of slowing down a disease similar to that of the Alzheimer’s Dementia. one-point estimate of the MMRM.
“As a clinician and researcher, I am very encouraged by the reduction of plaque that slows down and slows down clinical decline with donanemab,” said Stephen P. Salloway, MD, MS, director, Program Memory and Aging, and Martin M. Zucker Professor of Psychology and Human Behavior, Department of Neurology, Warren Alpert School of Medicine, Brown University, in a statement.2 “The donanemab findings are an important and inspiring milestone for people on the Alzheimer’s disease has taken its toll and we want to continue this fight. “