The Center for Drug Evaluation (CDE) website indicates that US major Eli Lilly’s (NYSE: LLY) donanemab has obtained tacit clinical trial approval for assessment in treating early symptomatic Alzheimer’s disease (AD), including mild cognitive impairment due to AD, and mild AD. This approval marks a significant step forward in the development of new drugs targeting amyloid, one of the important directions for Alzheimer’s disease research.
Drug Mechanism
Donanemab is a monoclonal antibody (mAb) that binds to the beta amyloid subtype N3pG in amyloid deposits in the brains of AD patients, promoting the clearance of these deposits. This mechanism of action aligns with the amyloid hypothesis, which suggests that the accumulation of amyloid plaques in the brain is a key driver of Alzheimer’s disease progression.
Clinical Trial Background
Donanemab previously reached primary endpoints in a Phase II clinical study, which enrolled 272 early AD patients randomized to receive donanemab and placebo. In this trial, researchers used the Integrated Alzheimer’s Disease Scale (iADRS) to comprehensively assess patients’ cognitive abilities and activities of daily living. The results showed that after 76 weeks of treatment, patients in the donanemab group had a 32% reduction in iADRS scores compared to the placebo group, meeting the trial’s primary endpoint.
Trial Outcomes
After six months of treatment, 40% of patients had negative PET tests, indicating that their levels of amyloid deposits in the brain were not significantly different from healthy people. After 18 months of treatment, 68% of patients achieved a negative PET test. These results highlight the potential of donanemab to not only improve symptoms but also to modify the underlying disease pathology.
Regulatory and Development Status
Based on the Phase II study results, the drug was awarded a breakthrough therapy designation (BTD). Lilly has initiated rolling submission with the US FDA and will carry out a confirmatory study to assess the preventative effects. This ongoing development and regulatory process underscores the potential of donanemab to become a valuable treatment option for patients with early symptomatic Alzheimer’s disease.-Fineline Info & Tech
