Pharmaceutical company Eli Lilly has announced the Phase 3 TRAILBLAER-ALZ 2 study showing that donanemab significantly slowed the progression of cognitive and functional decline in people with early symptoms of Alzheimer’s disease.
As indicated by the pharmaceutical company, donanemab, a treatment still in the investigation phase aimed at the amyloid plaque removal, met the primary endpoint of change from baseline to 18 months on the Integrated Alzheimer’s Disease Assessment Scale (iADRS). The iADRS scale allows to assess the cognition and performance of activities of daily livingsuch as managing finances, driving, participating in leisure activities, and discussing everyday events.
Likewise, all the secondary objectives of cognitive and functional impairment of the study were also met, demonstrating, in a statistically significant manner, the clinical benefits of donanemab. Based on these results, Lilly will work with the FDA and other global regulators to get the drug approved in the shortest time possible.
Onanemab treatment significantly slows the progression of cognitive and functional decline in people with early symptoms of Alzheimer’s
The randomized, double-blind, placebo-controlled study TRAILBLAZER-ALZ 2 enrolled people with early symptoms of Alzheimer’s disease (EA), who presented mild cognitive impairment (MCI) and mild dementia, in which Alzheimer’s neuropathology had been confirmed. Participants ended their donanemab treatment course once a pre-specified level of amyloid plaque clearance in the brain had been achieved.
The population in which the primary endpoint of the study was evaluated was composed of people with an intermediate level of tau and clinical symptoms of Alzheimer’s disease (n = 1,182). In this population, the iADRS scale showed a delay in cognitive decline of 35% (p00001 and one of the most relevant secondary objectives, specifically, through the use of the Clinical Assessment of Dementia scale or CDR-SB, for its acronym in English, showed a reduction in progression of 36% (p0.0001) in this same variable after 18 months of treatment.In turn, various additional secondary analyzes show that:
- 47% of participants treated with donanemab did not show worsening on the CDR-SBa key measure to assess the progression of disease severity at one year, compared with 29% of placebo participants (p0001li>
- 52% of the participants completed their treatment cycle in one year and 72% in 18 months, after achieving amyloid plaque removal.
- Patients who received donanemab had a 40% less progression in deterioration in ability to perform activities of daily living at 18 months (measured using the Alzheimer’s Disease Cooperative Study Instrumental Inventory of Activities of Daily Living: (ADCS-iADL), p00001]li>
- Donanemab patients had 39% less risk of progressing to the next stage of the disease compared with those who received placebo (CDR-Global Score, HR=0.61; p0001li>
As highlighted by the Dr Daniel SkovronskyMD, Lilly’s Chief Scientific and Medical Officer and President of Lilly Research Laboratories, “Over the past 20 years, Lilly scientists have opened new paths in the fight against Alzheimer’s disease by elucidating the basic mechanisms of its pathology and developing neuroimaging tools and blood biomarkers to track the disease”.
“We are very proud that the donanemab study has obtained positive clinical results, with high statistical significance. This is the first Phase 3 trial of any investigational drug for Alzheimer’s disease to demonstrate a 35% reduction in progression in clinical and functional deterioration«notes Dr. Skovronsky.
On the other hand, fewer people with high and medium tau levels at baseline were also included (n = 552), representing a more advanced stage in disease progression. In this combined population, donanemab also demonstrated significant positive results across all clinical endpoints (p0001 with CDR-SB and iADRS, showing a delayed clinical deterioration by 29% and 22%, respectively.
For his part, he Dr Mark MintunMD, vice president of the therapeutic area of pain and neurodegeneration at and president of Avid Radiopharmaceuticals, indicates that “These results suggest that people in the early stage of the disease might benefit more from targeted amyloid removal therapies. For this reason, we must thank the participants in the clinical trial and their families for their time and commitment in the search for solutions for this pathology.”.
In addition to delaying and functional in TRAILBLAZER-ALZ 2, donanemab produced significant reductions in amyloid plaque levels evidenced even 6 months after starting treatment. To this is added that many patients reached amyloid levels considered negative for pathology (34% of participants in the intermediate tau population achieved amyloid clearance at 6 months and 71% achieved clearance at 12 months).