What Is Donanemab?
Donanemab is an investigational drug currently being studied for the treatment of Alzheimer's disease and related neurodegenerative conditions. It is administered as an intravenous (IV) infusion. Clinical trials are exploring its potential to impact the progression of these diseases.
The drug is being investigated primarily for Alzheimer Disease, with 9 trials focused on this condition. Other related conditions under study include Dementia, Brain Diseases, Central Nervous System Diseases, and Neurodegenerative Diseases. Its development is primarily sponsored by Eli Lilly and Company.
Donanemab is typically given as an IV infusion, often on an every 4-week schedule. Some studies involve an up-titration regimen to reach a target dose, such as 1400 mg within 24 weeks. The first trial involving donanemab began on 2017-12-08, and the latest trial is projected to conclude on 2025-09-11. Across 13 total trials, donanemab has involved approximately 15,000 participants. Currently, 2 trials are recruiting new participants, while 5 trials have been completed.
Uses and Conditions Under Study
Donanemab is primarily being studied for its potential to treat conditions affecting the brain and nervous system, particularly those related to cognitive decline and neurodegeneration.
Alzheimer's Disease and Preclinical Alzheimer's Disease: This is the main focus of donanemab research. Alzheimer's disease is a progressive neurodegenerative disorder that causes brain cells to waste away and die, leading to memory loss and cognitive decline. Donanemab is being investigated to see if it can slow or halt this progression. A total of 9 trials are specifically studying Alzheimer Disease, with an additional 1 trial focusing on Preclinical Alzheimer's Disease, which involves individuals who may be at risk but do not yet show full symptoms.
Dementia and Neurocognitive Disorders: Beyond Alzheimer's, donanemab is also being explored for broader categories of cognitive impairment. Dementia refers to a group of symptoms affecting memory, thinking, and social abilities severely enough to interfere with daily life. Neurocognitive disorders encompass a range of conditions that involve impaired cognitive function. There are 3 trials investigating donanemab for Dementia and 2 trials for Neurocognitive Disorders, suggesting a potential role across various forms of cognitive decline.
Broader Neurological Conditions: The drug's potential is also being assessed in wider categories of neurological health. This includes 3 trials for Brain Diseases, 3 trials for Central Nervous System Diseases, 2 trials for Neurodegenerative Diseases, 2 trials for Mental Disorders, and 2 trials for Nervous System Diseases. These studies aim to understand donanemab's effects on the brain and nervous system more broadly.
Studies in Healthy Participants: Donanemab has also been studied in 2 trials involving healthy participants. These types of studies are typically conducted to understand how the drug is absorbed, distributed, metabolized, and excreted by the body (pharmacokinetics) and to assess its safety profile in individuals without the target disease.
Dosing
Donanemab is administered as an intravenous (IV) infusion. The specific dosing regimen can vary across clinical trials, as researchers investigate the most effective and safe ways to use the drug.
Commonly studied administration involves an IV infusion given every 4 weeks. Some studies utilize an up-titration regimen, where participants start at a lower dose and gradually increase to a target dose. For example, some regimens aim to reach a target dose of 1400 mg within 24 weeks.
Various strengths of donanemab have been investigated in clinical trials. These include:
- 350 mg Donanemab
- 700 mg Donanemab
- 1400 mg Donanemab
Trials have also explored different dosing strategies, such as a standard regimen, dose skipping, and titration protocols to understand the drug's pharmacokinetics and optimal therapeutic window. Donanemab has been studied both as monotherapy and in combination with other investigational agents, such as LY3202626 and RG6289, to assess potential synergistic effects or different treatment approaches for conditions like Alzheimer's disease.
Side Effects
The most common side effects observed in clinical trials for Donanemab involved amyloid-related imaging abnormalities (ARIA), which are changes seen on brain scans. These abnormalities are typically detected by MRI scans and may or may not cause symptoms. In studies involving 999 patients, 23.7% of patients taking Donanemab experienced amyloid-related imaging abnormality-oedema/effusion (ARIA-E), compared to 1.8% of patients on placebo. Another type of ARIA, amyloid-related imaging abnormality-microhaemorrhages and haemosiderin deposits (ARIA-H), occurred in 17.8% of patients on Donanemab, compared to 6.9% on placebo.
Other common side effects reported in clinical trials (n=999 drug arm) included:
- Headache: 12.9% of patients on Donanemab experienced headache, compared to 10.1% on placebo.
- Infusion-related reactions: 8.2% of patients on Donanemab experienced infusion-related reactions, compared to 0.4% on placebo.
- Superficial siderosis of the central nervous system: 7.9% of patients on Donanemab experienced this, compared to 1.4% on placebo.
In a smaller trial (n=146 drug arm), 10.3% of patients taking Donanemab experienced nausea, compared to 3.2% on placebo.
Clinical Trial Results
Clinical trials for Donanemab have investigated its effects on amyloid plaque reduction and the progression of Alzheimer's disease.
TRAILBLAZER-ALZ (NCT03367403)
In a study of participants with early symptomatic Alzheimer's disease, Donanemab demonstrated a significant reduction in brain amyloid plaque. Participants treated with Donanemab experienced an average reduction of 84.13 centiloids in amyloid plaque deposition, while those on placebo showed a slight increase of 0.93 centiloids. Donanemab also slowed the decline in daily activities, with a change of -3.98 on the Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living Scale (ADCS-iADL), compared to -5.20 for placebo, where a smaller negative change indicates slower decline. Additionally, Donanemab slowed overall disease progression as measured by the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB), with a score change of 1.22 for Donanemab compared to 1.58 for placebo, indicating slower progression.
TRAILBLAZER-ALZ 2 (NCT04437511)
This study further confirmed Donanemab's impact on amyloid plaque and disease progression in early Alzheimer's disease. Donanemab treatment led to a substantial reduction in brain amyloid plaque deposition, with an average change of -87.03 centiloids, compared to -0.67 centiloids for placebo. For the overall study population, Donanemab slowed the decline in daily activities, showing a change of -4.42 on the ADCS-iADL score, versus -6.13 for placebo. Donanemab also slowed overall disease progression, with a CDR-SB score change of 1.72 for Donanemab compared to 2.42 for placebo. In terms of immun
Currently Recruiting Trials
For individuals interested in contributing to the advancement of Alzheimer's disease research, two important studies for donanemab are currently seeking participants. These trials aim to gather more information on donanemab's effectiveness and safety in patients with early symptomatic Alzheimer's disease.
One ongoing study, NCT06566170, is a real-world comparative study sponsored by Eli Lilly and Company. This observational cohort study evaluates the long-term effectiveness of donanemab when combined with usual care, compared to usual care alone, in US participants diagnosed with early symptomatic Alzheimer's disease. Designed to reflect real-world clinical practice, this study is targeting an enrollment of 6250 participants.
Another significant trial, NCT05508789, known as TRAILBLAZER-ALZ 5, is a Phase 3 study also sponsored by Eli Lilly and Company. This trial is assessing the safety and efficacy of donanemab in participants with early Alzheimer's disease. The study involves a comprehensive evaluation period, including screening and follow-up, lasting up to 93 weeks. Researchers aim to enroll approximately 1500 participants for this important investigation into donanemab's potential benefits.
Where to Participate
Currently, opportunities to participate in donanemab clinical trials are available in a limited number of locations. For the recruiting trials, one site is active in the United States.
- Huntsville, Alabama
Eligibility criteria for these studies generally include individuals aged 60 to 85 years, of all genders. It is important to note that these trials are not seeking healthy volunteers or children; participants must have a diagnosis of early symptomatic Alzheimer's disease to be considered.
Development Timeline
The journey of donanemab began with its first clinical trial on December 8, 2017, marking the start of its extensive development. Over the years, Eli Lilly and Company has been the primary sponsor, leading 10 of the 13 total trials, with other institutions like Banner Health and individual researchers also contributing. The latest projected trial completion is September 11, 2025.
Initially, donanemab's research explored conditions such as IBS-C and hyperphosphatemia. However, the focus quickly shifted and significantly expanded to a wide range of neurological conditions, particularly those related to Alzheimer's disease. The pipeline grew to include studies for Brain Diseases, Central Nervous System Diseases, Neurodegenerative Diseases, and various forms of Alzheimer's, such as Preclinical Alzheimer's Disease, Prodromal Alzheimer's Disease, and Autosomal Dominant Alzheimer's Disease. Research also broadened to include conditions like Tauopathies, Amyloid Beta Protein, Cognitive Impairment, and even Down Syndrome, reflecting a comprehensive approach to neurodegenerative disorders.
Donanemab's development has progressed through various phases, including Phase 1, Phase 2, and most notably, 5 trials reaching Phase 3, indicating advanced stages of clinical investigation. To date, the trials have aimed to enroll a total of approximately 15,000 participants, demonstrating a substantial commitment to understanding the drug's potential.