Eli Lilly announces the complete phase III data of new drugs for Alzheimer's disease, which may compete with Eisai at the end of the year

TRAILBLAZER-ALZ2 Design of experiments and summary of results. Image source: Journal of the American Medical AssociationOn July 17 local time, the United States Lilly (LLY

TRAILBLAZER-ALZ2 Design of experiments and summary of results. Image source: Journal of the American Medical Association

On July 17 local time, the United States Lilly (LLY. US) announced that it had submitted the marketing application of the new Alzheimer's disease drug Donanemab to the Food and Drug Administration (FDA), which is expected to make a decision by the end of 2023. In addition, Lilly is submitting documents to other global regulatory agencies, most of which will be completed by the end of the year.

If fully approved, Donanemab will become the second "milestone" after Leqembi (commonly known as Lecanemab) jointly developed by Eisai and Biogen in the United States. At the beginning of July, FDA fully approved Leqembi's listing, which opened the door to Health insurance in the United States for people with indications of the drug (patients with Mild cognitive impairment or mild dementia stage of Alzheimer's disease).

Lilly announced its submission of documents to FDA at the International Meeting of the Alzheimer's Association (AAIC) held in the Netherlands this weekend, and presented the complete data of the three phase trial TRAILBLAZER-ALZ2, which were also published in the Journal of the American Medical Association (JAMA).

In May this year, the topline data released by Eli Lilly and Company Company showed that Donanemab slowed down the cognitive and functional decline of some patients with early Alzheimer's disease by 35% within 18 months. According to Leqembi's Phase 3 key clinical trial data, it slowed down the cognitive and functional decline rate of Alzheimer's disease patients by 27% within 18 months. Leqembi is administered every two weeks, and Donanemab is administered every four weeks.

In TRAILBLAZER-ALZ 2 of the Lilly Phase 3 trial, subgroup analysis results showed that Donanemab was more beneficial for participants in the early stages of the disease. Compared with placebo subjects, the cognitive and functional decline of subjects receiving Donanemab treatment was slowed by 60%. The Clinical Dementia Rating Scale (CDR-SB) showed a 46% reduction in cognitive decline in patients.

The performance of Donanemab is related to the age of the participants. In the population under 75 years old, the Alzheimer's Disease Comprehensive Rating Scale (iADRS) showed a 48% decrease in clinical decline rate and a 45% decrease in CDR-SB; For participants aged 75 or above, these two numbers are 25% and 29%, respectively.

The side effects of Donanemab are more pronounced, with 3 patients in the Phase 3 trial experiencing amyloid associated imaging abnormalities (ARIA) and subsequent death. ARIA may manifest as brain swelling, small bleeding inside or on the surface of the brain. Previously, Eli Lilly and Company had confirmed that two of the deaths were related to ARIA, and they suspected that the third one was also related to ARIA.

13.1% of patients using Donanemab stopped treatment due to adverse events (including injection reactions and ARIA-E). Although the patient enrollment criteria are different and the cross trial comparison is far from perfect, in contrast, 6.9% of patients in Leqembi's Phase III trial stopped treatment due to adverse events.

The diversity of Donanemab's Phase III clinical trial is insufficient: the number of Colored recruited in the trial is very small, and the results of the race and ethnic subgroups other than white people are not statistically significant.

We have a very small number of people in these groups and a very wide confidence interval, "Mark Mintun, Vice President of Neuroscience Research and Development at Lilly, said at a press conference.

Of the 1251 participants from the United States, only two were American Indians or Alaska Natives, 11 were Asian, 34 were black, and 71 were Hispanic.

"This Donanemab experiment did not provide enough evidence to prove the safety or effectiveness of American Indians or Alaska Natives, Asians, blacks or Hispanic," Jennifer Manly, a professor of Neuropsychology at Columbia University, and Professor Kacie Dieters at UCLA wrote in an editorial, "In view of the fact that many people in these groups suffer disproportionate cognitive impairment and Disease burden due to Alzheimer's disease, it is important for clinicians, patients and families to understand the limitations of known diseases."

Mintun said that in an upcoming safety trial and a prevention study targeting individuals at risk of Alzheimer's disease, Lilly has increased racial and ethnic diversity in patient recruitment.

In addition, the study also limited the age of participants to 85 years old, but doctors pointed out that the drug may be used in older adults than in the real world.

Setting aside the debate about safety and efficacy, amyloid antibodies will shift from strictly controlled clinical trials to the real world in 2023. What is important now is to obtain data, no matter how imperfect, and implement it in different populations, "Eric Widera and colleagues at the University of California, San Francisco wrote in an accompanying editorial at JAMA.

References:
https://endpts.com/eli-lilly-submits-donanemab-to-fda-as-it-shares-full-phiii-results-at-medical-meeting/

Disclaimer: The content of this article is sourced from the internet. The copyright of the text, images, and other materials belongs to the original author. The platform reprints the materials for the purpose of conveying more information. The content of the article is for reference and learning only, and should not be used for commercial purposes. If it infringes on your legitimate rights and interests, please contact us promptly and we will handle it as soon as possible! We respect copyright and are committed to protecting it. Thank you for sharing.(Email:[email protected])