A positive Phase 2 trial brings hope to millions of people suffering from Alzheimer’s Disease. It seems almost impossible to accept that Alzheimer’s Disease and related memory loss and impairment from dementia have commanded countless billions of dollars of drug research without a single approved drug on the market anywhere yet. More than 5 million Americans alone suffer from Alzheimer’s today and that number expected to rise to nearly 14 million by 2050. The entire world is eagerly awaiting any treatment that can receive drug approval of some sort.
On January 11, 2021, Eli Lilly and Company announced encouraging results in their Phase 2 TRAILBLAZER-ALZ study of the experimental antibody donanemad. It targets a modified form of beta amyloid called N3pG, which is the main component of the amyloid plaques found in the brains of people with Alzheimer’s disease. The trial enrolled 272 patients who were selected based on cognitive assessments in conjunction with amyloid plaque imaging and tau imaging.
Patients with early symptomatic Alzheimer’s disease responded positively to Denanemad. The Integrated Alzheimer’s Disease Rating Scale (iADRS) is a clinical composite tool combining the cognitive measure ADAS-Cog13 and functional measure ADCS-iADL, two commonly used measures in Alzheimer’s disease. The investigational antibody showed a significant slowing decline of 32% in a composite measure of cognition and daily function, compared to placebo.
Donanemab treatment showed rapid results in high levels of amyloid plaque clearance. On average, patients showed an 84 centiloid reduction of amyloid plaque at 76 weeks compared to a baseline of 108 centiloids (less than 25 centiloids is typical of a negative amyloid scan). The safety profile of donanemab was consistent with observations from Phase 1 data.
TRAILBLAZER-ALZ is a randomized, placebo-controlled, double-blind, multi-center Phase 2 study to assess the safety, tolerability and efficacy of donanemab in patients with early symptomatic Alzheimer’s disease.
Eli Lilly plans to reproduce and extend these important findings in a second ongoing pivotal trial using donanemab, called TRAILBLAZER-ALZ 2. In addition, TRAILBLAZER-EXT is an ongoing trial for those who participated in TRAILBLAZER-ALZ. The full results of the TRAILBLAZER-ALZ study will be presented and submitted for publication in a peer-reviewed clinical journal. Lilly will discuss these results with regulators to assess next steps for donanemab.
Alzheimer’s is not just a domestic issue. It is estimated that approximately 70 million to 100 million people have early Alzheimer’s disease where they have mild cognitive impairment and/or mild dementia stages. The Alzheimer’s Association covers the statistics and other data in much more detail.
This is not the first bit of good news on the Alzheimer’s treatments showing promise. A recent study from Denmark’s Novo Nordisk is also entering Phase 3 trials. Perhaps one of these two treatments may be able to reach the market for this entirely unmet need.