Source – Eli Lilly
The full data from Eli Lilly’s TRAILBLAZER-ALZ 2 trial of the amyloid drug donanemab has validated the previously reported top-line results from May and has also revealed new findings that further support its effectiveness in treating Alzheimer’s disease.
During the Alzheimer’s Association International Conference (AAIC) presentation, the updated data confirmed the earlier findings that donanemab slowed the decline in cognitive function by 35% using the iADRS scale and 36% using the CDR-SB scale, as compared to the placebo.
The new information from the study revealed that participants with earlier-stage Alzheimer’s experienced the greatest benefits. Specifically, they saw a remarkable 60% improvement with donanemab compared to the control group on the iADRS scale and 46% improvement on the CDR-SB scale. Nearly half (47%) of these participants showed no signs of clinical progression after one year.
“The delay of disease progression over the course of the trial is significant and will give people more time to do such things that are meaningful to them,” said Liana Apostolova of Indiana University School of Medicine, one of the TRAILBLAZER-ALZ 2 investigators.
Moreover, the data demonstrated that the positive treatment effect of donanemab continued to increase over the course of the trial compared to the placebo, with the most significant difference observed at 18 months, even though donanemab treatment was only continued until amyloid plaques were cleared from the brain.
On average, the slowdown in cognitive decline allowed patients to have an additional seven and a half months before reaching the same level of decline as the control group.
Patients aged under 75 also showed better results, and the drug’s effects were consistent regardless of whether they carried the ApoE4 gene mutation, a risk factor for Alzheimer’s disease. However, donanemab had limited effect in individuals with high levels of tau protein, which suggests they were likely in more advanced stages of the disease.
Treatment with donanemab led to an average 84% reduction in amyloid plaque burden at 18 months, in comparison to a 1% decrease in the placebo group. Approximately half of the patients receiving the antibody were able to discontinue treatment after 12 months, increasing to around 70% at 18 months, indicating the potential for intermittent treatment with ‘off-drug’ periods to minimize side effects and potentially reduce costs.
“With this fuller picture, there is additional, convincing scientific evidence that thoroughly removing beta-amyloid from the brain is associated with significant slowing of disease progression in people living with early Alzheimer’s.”
– Maria Carrillo, chief scientific officer at the Alzheimer’s Association
Regarding side effects, the level and severity of potentially life-threatening amyloid-related imaging abnormalities (ARIA), a known risk associated with amyloid drugs, were consistent with the earlier results. The investigators, however, noted that these side effects could be managed through monitoring and discontinuation of treatment if necessary.
Significantly, this data aligns with and reinforces the positive outcomes observed with Eisai and Biogen’s amyloid-targeting drug, Leqembi (lecanemab), in the CLARITY-AD study, which led to the drug securing full FDA approval as the first drug in its class.
With pivotal trials now demonstrating clinical benefits in cognition and functional scores, there is increased confidence that targeting amyloid can genuinely have a disease-modifying effect.
These findings support the long-held belief that early treatment will be crucial for unlocking the maximum benefits of these drugs and also suggest potential for slowing disease progression even when treatment is initiated later on.
