Donanemab shows promise as a treatment for Alzheimer’s disease

This article was originally published on Neurology Live.

Donanemab may provide a better composite score for cognition and ability to perform activities of daily living after 76 weeks compared to placebo in patients with early-stage Alzheimer’s disease. New England Journal of Medicine Announced at AD / PD2021.

The main results are changes from baseline in the scores of the Integrated Alzheimer’s Disease Rating Scale (iADRS), ranging from 0 to 144, indicating that lower scores indicate greater cognitive dysfunction. At baseline, the iADRS score was 106 in both the donanemab (n = 131) group and the placebo (n = 126; one participant was excluded from the modified ITT population) group.

After 76 weeks, the score in the treatment group changed by –6.86 points and the score in the placebo group changed by -10.06 (difference, 3.20; 95% CI, 0.12-6.27; P = .04). This change corresponded to a 32% difference in slowing decline in the donanemab group, a significant difference identifiable by 9 months.

“We are confident in the results of the TRAIL BLAZER-ALZ study,” said Dr. Daniel Skovlonski, MD, chief scientific officer and president of the Eli Lilly and Company’s Lily Institute, the developer of Donanemab, in a statement. Stated. In the first late trial of Alzheimer’s disease, the primary analysis met the primary endpoint. Donanemab can be a very important treatment for Alzheimer’s disease.

“We are pleased to see not only a delay in cognitive decline, but also a very substantial clearance of amyloid plaques and a delay in the spread of tau pathology,” Skovronsky added. We would like to thank the patients, caregivers and researchers for participating in this groundbreaking study. “

At week 76, the reduction in amyloid plaque levels was 85.06 centiroids (-84.13 vs. 0.93) greater with donammab than with placebo.

Almost asymptomatic amyloid-related cerebral edema or exudate (ARIA-E) occurred with donanemab treatment. As early as 6 months, 40% of patients treated with donammab achieved amyloid negative (defined as amyloid plaque levels below 24.10 centiroids), and 68% achieved this in 18 months. The proportion of participants in the amyloid-negative group at 24, 52, and 76 weeks was 40.0%, 59.8%, and 67.8%, respectively.

“The combination of changes in the biomarkers of Alzheimer’s disease and the slowing of clinical manifestations of the disease seen in this study is promising,” said Howard, founding executive director and chief scientific officer of the Alzheimer’s Disease Drug Discovery Foundation (ADDF). Dr. Philit said in a statement. To the data. “Encouraged by today’s news and confirming these results in a large ongoing study, donanemab offers potential disease-modifying therapies to help patients maintain their cognitive abilities and independence longer. May be. Future exams. “

In the safety population, 90.8% (n = 119) of the donanemab group and 90.4% (113/125) of the placebo group experienced at least one adverse event (AE) during 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). Symptomatological ARIA-E was reported by 6.1% of all participants in the donanemab group (22% of ARIA-E participants) compared to 0.8% of all participants in the placebo group.

Most cases of ARIA-E occurred at or by the 12th week of the intervention period, and severe symptomatological cases (n = 2; 1.5%) occurred in the donanemab group. Symptoms resolved on average in 18 weeks in both of these patients.

The results of the secondary results of the study were mixed. These measurements include the clinical dementia rating scale-box total (CDR-SB), the 13-item cognitive subscale of the Alzheimer’s disease rating scale (ADAS-Cog13), and the Alzheimer’s disease collaborative research-device activity score. The change was included. Changes in amyloid and tau burden in activities of daily living inventory (ADCS-iADL), Mini-Mental State Examination (MMSE), and Positron Emission Tomography (PET).

Differences between the donanemab and placebo groups in changes from baseline at week 76 were -0.36 (95% CI, -0.83 to 0.12), -1.86 (95% CI, -3.63 to -0.09) in CDR-SB scores. was. For ADAS-Cog13 scores, 1.21 (95% CI, -0.77 to 3.20) for ADCS-iADL scores and 0.64 (95% CI, -0.40 to 1.67) for MMSE scores.

Lead Author Mark A. Minton, MD, Vice President of Pain and Neurodegeneration Research and Clinical Development at Eli Lilly and Company. President Avid Radiopharmaceuticals and colleagues have selected several dosing regimens (700 mg for the first three doses, then 1400 mg) to facilitate aggressive removal of amyloid plaques. He said it was worth considering the features.

In addition, all participants must meet the Flortaus pill PET screening criteria, which “may have narrowed the scope of the underlying pathological features and thus reduced the variability of clinical decline,” and the level of tau Excluded the highest person.

When the trial followed the model of disease progression proposed by the European Alzheimer’s disease prevention project, Minton et al. Stated that they produced estimates of disease slowdown similar to single-point estimates of MMRM.

“As a clinician and researcher, I am particularly encouraged by the significant reduction in plaque and slowing clinical decline with donanemab,” said Stephen P. Sarroway, MD and Martin M., Director of the Memory and Aging Program. Professor Zucker said. Brown University Warren Alpart Medical School Department of Neurology Psychiatry and Human Behavior Statement 2 “The results of Donanemab are important and encouraging milestones for people affected by Alzheimer’s disease and we want to continue this fight. “”