What is the mechanism of action of this treatment?

The most common treatments for Alzheimer's Disease include cholinesterase inhibitors (such as donepezil, rivastigmine, and galantamine), NMDA receptor antagonists (like memantine), and monoclonal antibodies targeting amyloid-beta plaques (such as donanemab). Cholinesterase inhibitors work by increasing levels of acetylcholine, a neurotransmitter important for memory and learning, thereby providing modest symptomatic relief. NMDA receptor antagonists help regulate glutamate activity to prevent excitotoxicity, which can damage neurons. Monoclonal antibodies like donanemab target and help clear amyloid-beta plaques, which are believed to play a key role in the pathogenesis of Alzheimer's. These treatments are crucial as they aim to alleviate symptoms and potentially modify disease progression, improving the quality of life for patients.

What side effects are associated with this type of intervention?

Common treatments for Alzheimer's Disease, particularly antibody therapies targeting amyloid-beta plaques like Donanemab, often have side effects including local injection site reactions (e.g., erythema, pain, or bruising), hypersensitivity reactions (e.g., rash, pruritus, urticaria), and rare serious allergic reactions. Cholinesterase inhibitors, another common treatment, can cause gastrointestinal issues, muscle cramps, and insomnia. Memantine, used for moderate to severe Alzheimer's, may lead to dizziness, headache, confusion, and constipation. It is important to discuss these potential side effects with a healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

The FDA has approved several treatments for Alzheimer's Disease that target amyloid-beta plaques, similar to Donanemab. One notable example is Aducanumab, a monoclonal antibody that reduces amyloid-beta plaques in the brain. Aducanumab is administered via intravenous infusion and requires regular brain MRI monitoring due to the risk of amyloid-related imaging abnormalities (ARIA). Other treatments for Alzheimer's Disease include vitamin E and selegiline, although these do not specifically target amyloid-beta plaques and have shown mixed results in clinical trials.

What other types of research exist?

Promising novel alternatives to Donanemab for Alzheimer's Disease patients in 2024 include: 1) Lecanemab, another antibody targeting amyloid-beta plaques, which has shown efficacy in slowing cognitive decline. 2) Aducanumab, an FDA-approved antibody that also targets amyloid-beta plaques. 3) Tau-targeting therapies such as anti-tau antibodies (e.g., semorinemab) and tau aggregation inhibitors. 4) BACE inhibitors like verubecestat, which reduce amyloid-beta production. 5) Neuroprotective agents and anti-inflammatory drugs that target other pathways involved in Alzheimer's pathology.

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Monoclonal Antibodies

Donanemab for Early Alzheimer's Disease

Phase 3

Waitlist Available

Research Sponsored by Eli Lilly and Company

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Must not have

Current treatment with immunoglobulin G (IgG) therapy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up week 16 to week 20

Awards & highlights

Pivotal Trial

Summary

This trial is testing donanemab, a drug for early Alzheimer's disease. It targets people with early symptoms and specific brain changes. The drug helps remove harmful proteins from the brain, potentially slowing down or improving symptoms.

Who is the study for?

This trial is for people with early Alzheimer's who've had memory changes for at least 6 months, scoring 20-28 on the MMSE (a cognitive test). They must meet specific criteria on PET scans and have a partner to consent to participate. Those who can't undergo MRI or PET scans or are currently on IgG therapy cannot join.

What is being tested?

The study is testing the safety and effectiveness of Donanemab in treating early Alzheimer's disease. Participants will either receive Donanemab or a placebo. An additional group will be openly given Donanemab to assess its safety further.

What are the potential side effects?

While not explicitly listed here, potential side effects may include reactions related to immune system activation, as it is common with monoclonal antibodies like Donanemab.

Eligibility Criteria

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I am currently receiving IgG therapy.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ week 16 to week 20

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~week 16 to week 20

This trial's timeline: 3 weeks for screening, Varies for treatment, and week 16 to week 20 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change From Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS) (Intermediate (Low-medium) Tau Population)

Change From Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS) (Overall Population)

Secondary study objectives

Change From Baseline in Brain Amyloid Plaque Deposition as Measured by Amyloid Positron Emission Tomography (PET) Scan

Change From Baseline in Brain Tau Deposition as Measured by Flortaucipir F18 PET Scan

Change From Baseline in Brain Volume as Measured by Volumetric Magnetic Resonance Imaging (vMRI)

+10 more

Side effects data

From 2023 Phase 3 trial • 148 Patients • NCT05108922

33%

Amyloid related imaging abnormality-oedema/effusion

25%

Amyloid related imaging abnormality-microhaemorrhages and haemosiderin deposits

19%

Covid-19

14%

Headache

10%

Superficial siderosis of central nervous system

Fall

Nausea

Fatigue

Benign prostatic hyperplasia

Diarrhoea

Back pain

Cataract

Dizziness

Infusion site extravasation

Upper respiratory tract infection

Tooth infection

Nasopharyngitis

Hypertensive urgency

Infusion related reaction

Gastroenteritis

Rotator cuff syndrome

Coronary artery disease

Muscle spasms

Sinusitis

Arthralgia

Chest pain

Rash

Oedema peripheral

Muscular weakness

Hypertension

Urinary tract infection

Sars-cov-2 test positive

Ageusia

Osteoarthritis

Hyperlipidaemia

Lymphocytosis

Non-cardiac chest pain

Gastritis

Ocular procedural complication

Muscle discomfort

Toothache

Bronchitis

Lower respiratory tract infection

Neck pain

Lacunar infarction

Peripheral artery aneurysm

Asthenia

Thrombocytopenia

Hyperbilirubinaemia

Cough

Spinal compression fracture

Infusion site reaction

Pain

Hyperglycaemia

Gait disturbance

Hypervolaemia

Transient ischaemic attack

Epiretinal membrane peel

Iron deficiency anaemia

Leukocytosis

Lymphopenia

Atrial fibrillation

Cardiomegaly

Tinnitus

Visual field defect

Eructation

Gastric polyps

Gingival swelling

Inguinal hernia

Conjunctivitis

Gastroenteritis viral

Influenza

Viral infection

Arthropod bite

Facial bones fracture

Pelvic fracture

Shoulder fracture

Skin abrasion

Blood cholesterol increased

Hepatic enzyme increased

Weight decreased

Hypomagnesaemia

Ejection fraction decreased

Hepatic enzyme abnormal

Hyponatraemia

Groin pain

Intervertebral disc protrusion

Joint swelling

Myalgia

Scoliosis

Basal cell carcinoma

Osteoma

Cerebral haemorrhage

Migraine

Neuropathy peripheral

Paraesthesia

Somnolence

Agitation

Confusional state

Depression

Initial insomnia

Mood altered

Nocturia

Pollakiuria

Urinary retention

Pulmonary mass

Dermatitis

Hyperkeratosis

Aortic aneurysm

Peripheral arterial occlusive disease

Parotid duct obstruction

Rash erythematous

Syncope

Cholecystitis

Gastrooesophageal reflux disease

Vomiting

Cerebral microhaemorrhage

Nerve compression

Anxiety

Depressed mood

Pain in extremity

Benign tumour excision

Atrioventricular block second degree

Anaemia

Haemarthrosis

Fibromyalgia

Bradycardia

Dysphagia

Obstructive sleep apnoea syndrome

100%

80%

60%

40%

20%

Study treatment Arm

Aducanumab

Donanemab

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: DonanemabExperimental Treatment1 Intervention

Participants received 700 milligram (mg) Donanemab every 4 weeks (Q4W) x 3 doses, then 1400 mg Q4W given intravenously (IV) for up to 72 weeks

Group II: PlaceboPlacebo Group1 Intervention

Participants received placebo given IV.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Donanemab

2017

Completed Phase 3

~500

0 / 1Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Alzheimer's Disease include cholinesterase inhibitors (such as donepezil, rivastigmine, and galantamine), NMDA receptor antagonists (like memantine), and monoclonal antibodies targeting amyloid-beta plaques (such as donanemab). Cholinesterase inhibitors work by increasing levels of acetylcholine, a neurotransmitter important for memory and learning, thereby providing modest symptomatic relief. NMDA receptor antagonists help regulate glutamate activity to prevent excitotoxicity, which can damage neurons. Monoclonal antibodies like donanemab target and help clear amyloid-beta plaques, which are believed to play a key role in the pathogenesis of Alzheimer's. These treatments are crucial as they aim to alleviate symptoms and potentially modify disease progression, improving the quality of life for patients.