Lilly Alzheimer's antibody therapy reaches the main clinical endpoint of Phase 2

In the last 15 years, however, a number of in-research therapies for Alzheimer's disease have been "folding sand" in the later stages of clinical development, including a variety of targeted β amyloid therapies.
, doubts have β whether the amyloid protein is the cause of cognitive decline in Alzheimer's patients.
But last year, Yanjian announced that its β amyloid antibody aducanumab had shown positive clinical results in Phase 3 clinical trials, and that its regulatory application had been approved as a priority by the FDA and was expected to be answered this spring.
's data on donanemab, which is now also targeting β amyloid, raises questions about how lilly's donanemab is different from other targeted therapies, as well as targeting β amyloid. Have we found the β to target starchy proteins? How far are we from an effective treatment for Alzheimer's disease? Today, the Pharmaceutical Mingkang content team will discuss these issues in conjunction with public information.
donanemab clinical trial results Let's first look at the performance of Donanemab in Phase 2 clinical trials, which included a total of 272 patients with early Alzheimer's disease.
patients were tested not only for cognitive abilities when they joined the clinical trial, but also for the deposition of amyloid and tau proteins in the brain through imaging.
were randomly grouped and treated with donanemab and placebo.
after 76 weeks of treatment, an analysis of comprehensive indicators assessing cognitive ability and daily function showed that the overall indicator of the donanemab group decreased by 32% compared to the placebo group, reaching the main endpoint of the trial.
, imaging tests of amyloid deposition showed a significant reduction in amyloid plaques in the brains of patients treated with donanemab.
76 weeks of treatment, the average level of amyloid plaques in the patient's brain dropped by 84 units using an assessment of amyloid levels called Centiloid.
their baseline level was 108, while a scan of less than 25 was considered negative, similar to that of healthy people.
's the difference between Donanemab and don't? Donanemab binds specifically to a amyloid protein subtype called N3pG, and by targeting this subtype, donanemab is able to specifically combine with amyloid plaques in the brain to facilitate the removal of amyloid plaques.
The "amyloid protein" hypothesis states that Alzheimer's disease is caused by the cutting of amyloid pregenes (APP) in the patient's brain to produce amyloid protein (A beta), which accumulates to produce 2 aggregates, oligomers, and eventually amyloid plaque deposits.
many of the strategies in the study therapy are to inhibit the production of A-beta, or the formation of 2 and oligomers.
, however, a study published in Neuron in 2012 showed that monoclonal antibodies that bind to A-beta monosomes do not perform as well as antibodies that specificly bind to amyloid plaques! This is due to the fact that monoclonal antibodies that bind to A-beta monomers, within the therapeutic dose range, bind to A-beta monomers and oligopolymers in blood and cerebrospinal fluid before binding to amyloid plaques, preventing them from binding to amyloid plaques.
antibodies that bind specific to amyloid plaques can bypass the "barriers" of A-beta monomers and oligomers and more effectively remove amyloid plaque deposits in the brain. Dr. Daniel Skovronsky, Chief Scientific Officer of Lilly,
Targeting Amyloid, said Donanemab's ability to quickly remove amyloid plaques and the company's expertise in amyloid and tau protein imaging technology allow researchers to detect the hypothesis that reducing amyloid plaques in Alzheimer's patients to the same levels as in healthy people can significantly delay cognitive decline.
positive results of this clinical trial have strengthened their confidence in this hypothesis.
If you look back at the results of the trial at aducanumab, PET scans found a greater reduction in amyloid levels in the brain and a significant delay in cognitive decline in alzheimer's patients who were able to continue to receive high doses of aducanumab.
these results seem to suggest that targeted amyloid proteins have not been successful in previous studies, possibly because they have not been able to reduce the deposition of amyloid plaques in the brain to a sufficiently low level.
this philosophy, Roche has conducted two Phase 3 clinical trials to test the effectiveness of high-dose amyloid antibody gantenerumab in early Alzheimer's patients.
monoclonal antibody tends to bind to aggregated A-beta proteins in the brain to degrade amyloid deposits by collecting small glial cells and activated macrophages.
company has also developed a "brain shuttle" technology that helps gantenerumab cross the blood-brain barrier to more effectively remove amyloid deposits in the brain.
the future of Alzheimer's disease, donanemab's clinical trial, which recruited only 272 patients, still needs to be validated in a Phase 3 clinical trial that includes more patients.
But data from aducanumab and donanemab also support a more accurate assessment of patients participating in clinical trials using amyloid and tau protein imaging, which may help to identify the efficacy of the treatment in study.
addition to targeted amyloid therapies, recent innovative treatments targeting inflammatory responses have also achieved positive results in phase 2b/3 clinical trials for Alzheimer's disease.
and Nord have also recently launched Phase 3 clinical trials to test the efficacy of its GLP-1 subject astration somatroptide in the treatment of Alzheimer's patients.
: This article is intended to introduce medical and health research, not treatment options recommended.
if you need guidance on treatment options, visit a regular hospital.
: s Donanemab Slows Clinical Decline of Alzheimer's Disease in Positive Phase 2 Trial. Retrieved January 11, 2021, from [2] Therapeutic development for Alzheimer’s disease at Eli Lilly and Company. Retrieved January 11, 2021, from [3] DeMattos et al, A Plaque-Specific Antibody Clears Existing b-amyloid Plaques in Alzheimer’s Disease Mice. Neuron,