FDA Approves Donanemab for Early Alzheimer's Disease (2024)

Table of Contents

1. What the FDA Did
2. Who the Approval Covers
3. How the Drug Works
4. The Trial Behind the Approval
5. What the 76-Week Results Showed
6. The Boxed Warning, Word for Word
7. How Often ARIA Occurred, and Who Was at Higher Risk
8. Other Warnings and Side Effects
9. What the Approval Does Not Do
10. The July 2025 Label Revision
11. Dates and Status as of 11 October 2026
12. How the Approval Fits the FDA’s Other Steps
13. Primary Documents
14. Key Research Papers
15. Connections

1. What the FDA Did

The FDA’s Center for Drug Evaluation and Research (CDER) posted the notice “FDA approves treatment for adults with Alzheimer’s disease,” content current as of 2 July 2024. It states that the agency “has approved [donanemab-azbt] injection for the treatment of Alzheimer’s disease” and that the drug “is administered as an intravenous infusion every four weeks.” (Product names are omitted on this page; the bracketed generic name stands in for the brand name the FDA uses.)

Donanemab is entry 22 on CDER’s list “Novel Drug Approvals for 2024,” dated 7/2/2024, with the use “To treat Alzheimer’s disease.” Because donanemab is a biologic (a medicine made by living cells), it was approved through a biologics license application rather than a new drug application; an FDA Federal Register notice of July 2025 identifies it as BLA 761248 and confirms the approval date of 2 July 2024.

The CDER notice states that the FDA granted the application Fast Track, Priority Review and Breakthrough Therapy designations, three FDA programs for drugs aimed at serious conditions. What each program means is set out on the site’s 2024 resmetirom page, which drew on the FDA’s own explanations of them.

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2. Who the Approval Covers

The indication in the prescribing information reads: the drug “is indicated for the treatment of Alzheimer’s disease. Treatment … should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in the clinical trials.” That sentence is the FDA-approved label wording, reported here as such.

• Amyloid confirmed first. The label’s first dosing step is to “confirm the presence of amyloid beta pathology prior to initiating treatment.” In the trial, everyone had confirmed amyloid pathology.
• Early stage only. The trial enrolled people with mild cognitive impairment or mild dementia, which the label describes as “consistent with Stage 3 and Stage 4 Alzheimer’s disease,” with a Mini-Mental State Examination (MMSE) score from 20 to 28 and a progressive change in memory for at least 6 months.
• A baseline MRI. The label calls for a recent baseline brain MRI before the first infusion and further MRIs before the 2nd, 3rd, 4th and 7th infusions, to look for ARIA.
• Genetic testing for risk. The label calls for testing for the ApoE ε4 gene variant before treatment “to inform the risk of developing ARIA” (see sections 6 and 7).

The CDER notice describes Alzheimer’s disease as “an irreversible, progressive brain disorder affecting more than 6.5 million Americans that slowly destroys memory and thinking skills and, eventually, the ability to carry out simple tasks,” characterized by amyloid beta plaques and tau tangles that result in loss of neurons and their connections.

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3. How the Drug Works

The label’s Mechanism of Action section states that donanemab-azbt “is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against insoluble N-truncated pyroglutamate amyloid beta. The accumulation of amyloid beta plaques in the brain is a defining pathophysiological feature of Alzheimer’s disease. Donanemab-azbt reduces amyloid beta plaques …” In plain terms, it is an antibody protein, produced in a cultured animal cell line (the label names a Chinese hamster ovary cell line), that binds to a modified form of amyloid found in the plaques.

The drug is meant to be stopped once plaques are cleared. The label states that prescribers may “consider stopping dosing … based on reduction of amyloid plaques to minimal levels on amyloid PET imaging” (PET is a brain scan that can show amyloid). In the trial, the share of donanemab patients who met the plaque-clearance threshold for switching to placebo was 17% at week 24, 47% at week 52 and 69% at week 76. The label adds that amyloid PET values may rise again after treatment stops, and that there is no data beyond the 76-week trial to show whether more dosing is needed for longer-term benefit.

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4. The Trial Behind the Approval

The FDA notice and label describe one double-blind, placebo-controlled, parallel-group trial (Study 1, registered as NCT04437511 and published as TRAILBLAZER-ALZ 2; see Key Research Papers):

• Size: 1,736 patients, randomized 1:1 to donanemab (860) or placebo (876), for up to 72 weeks.
• Trial dosing: 700 mg every 4 weeks for the first 3 doses, then 1,400 mg every 4 weeks. (This schedule was changed in July 2025; see section 10.)
• Stopping on plaque clearance: patients were switched to placebo, without being told, once amyloid PET showed a prespecified reduction at week 24, 52 or 76 — under 11 Centiloids (the unit used for amyloid PET) on one scan, or 11 to under 25 Centiloids on two scans in a row.
• Tau imaging: entry used tau PET imaging; 68% of patients had low or medium tau levels and 32% had high tau.
• Other medicines: patients could enroll with or without the existing approved Alzheimer’s drugs (cholinesterase inhibitors and memantine).
• Who took part: mean age 73 (range 59 to 86); 57% women; 91% White, 6% Asian, 4% Hispanic or Latino, 2% Black or African American; 71% carried at least one ApoE ε4 gene variant.

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5. What the 76-Week Results Showed

The main measure was the integrated Alzheimer’s Disease Rating Scale (iADRS), which combines a thinking-test score (ADAS-Cog13) and a daily-activities score (ADCS-iADL). It runs from 0 to 144, and the label notes that lower scores mean worse thinking and function. All scores worsened over 76 weeks in both groups; the drug’s effect is measured as a smaller decline than with placebo. The FDA notice reports these differences against placebo at week 76 in the overall trial population:

• iADRS: 2.92 points less decline (p<0.0001). In the low/medium-tau group the label reports 3.25 points (p<0.0001).
• ADAS-Cog13 (thinking): −1.33 (p=0.0006).
• ADCS-iADL (daily activities): 1.70 (p=0.0001).
• CDR-SB (Clinical Dementia Rating, Sum of Boxes): −0.70 (p<0.0001).

The published trial report gives the raw changes behind those differences. In the combined population the iADRS fell by 10.2 points on donanemab and 13.1 points on placebo; the CDR-SB, which runs from 0 to 18 with higher scores meaning greater impairment, rose by 1.72 on donanemab and 2.42 on placebo. Of 1,736 randomized participants, 1,320 (76%) completed the trial.

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6. The Boxed Warning, Word for Word

The CDER notice summarizes: “The prescribing information includes a boxed warning for amyloid-related imaging abnormalities (ARIA). ARIA most commonly presents as temporary swelling in areas of the brain that usually resolves over time and may be accompanied by small spots of bleeding in or on the surface of the brain. ARIA usually does not have symptoms, although serious and life-threatening events rarely can occur.”

The full boxed warning in the prescribing information approved in July 2024 (label revised 7/2024) reads as follows; only the brand name has been replaced with [donanemab]:

WARNING: AMYLOID RELATED IMAGING ABNORMALITIES

Monoclonal antibodies directed against aggregated forms of beta amyloid, including [donanemab], can cause amyloid related imaging abnormalities (ARIA), characterized as ARIA with edema (ARIA-E) and ARIA with hemosiderin deposition (ARIA-H). Incidence and timing of ARIA vary among treatments. ARIA usually occurs early in treatment and is usually asymptomatic, although serious and life-threatening events rarely can occur. Serious intracerebral hemorrhages >1 cm, some of which have been fatal, have been observed in patients treated with this class of medications. Because ARIA-E can cause focal neurologic deficits that can mimic an ischemic stroke, treating clinicians should consider whether such symptoms could be due to ARIA-E before giving thrombolytic therapy in a patient being treated with [donanemab] [see Warnings and Precautions (5.1), Adverse Reactions (6.1)].

ApoE ε4 Homozygotes

Patients who are apolipoprotein E ε4 (ApoE ε4) homozygotes (approximately 15% of Alzheimer’s disease patients) treated with this class of medications, including [donanemab], have a higher incidence of ARIA, including symptomatic, serious, and severe radiographic ARIA, compared to heterozygotes and noncarriers [see Warnings and Precautions (5.1)]. Testing for ApoE ε4 status should be performed prior to initiation of treatment to inform the risk of developing ARIA. Prior to testing, prescribers should discuss with patients the risk of ARIA across genotypes and the implications of genetic testing results. Prescribers should inform patients that if genotype testing is not performed, they can still be treated with [donanemab]; however, it cannot be determined if they are ApoE ε4 homozygotes and at higher risk for ARIA [see Warnings and Precautions (5.1)].

Consider the benefit of [donanemab] for the treatment of Alzheimer’s disease and potential risk of serious adverse events associated with ARIA when deciding to initiate treatment with [donanemab] [see Warnings and Precautions (5.1) and Clinical Studies (14)].

Some terms in it, as the label itself defines them: ARIA-E is brain edema (swelling) or sulcal effusions (fluid in the grooves of the brain) seen on MRI; ARIA-H is hemosiderin deposition, meaning microhemorrhages (tiny bleeds) and superficial siderosis (iron deposits from bleeding on the brain surface). “Homozygotes” are people with two copies of the ApoE ε4 variant; “heterozygotes” have one. Thrombolytic therapy is clot-dissolving treatment; the label gives tissue plasminogen activator as an example. The “should” sentences are the FDA-approved label’s instructions to prescribers, quoted as the label states them. The wording was revised in July 2025 (section 10).

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7. How Often ARIA Occurred, and Who Was at Higher Risk

The 2024 label’s Warnings and Precautions section reports these Study 1 figures (853 patients treated with donanemab, 874 on placebo):

• Any ARIA on MRI (including events without symptoms): 36% on donanemab vs 14% on placebo.
• ARIA-E (swelling): 24% vs 2%. ARIA-H (small bleeds or iron deposits): 31% vs 13%. The label notes no increase in ARIA-H occurring without ARIA-E.
• Symptomatic ARIA: 6% (52 of 853) of donanemab patients; symptoms resolved in about 85% (44 of 52). Reported symptoms include headache, confusion, visual changes, dizziness, nausea and difficulty walking; the label states that serious events, “including seizure and status epilepticus,” can occur.
• Brain hemorrhage larger than 1 cm: 0.5% (4 of 853) on donanemab vs 0.2% (2 of 874) on placebo. The label states that “fatal events of intracerebral hemorrhage in patients taking [donanemab] have been observed.”

ApoE ε4 status. In the donanemab arm, 17% were ApoE ε4 homozygotes, 53% heterozygotes and 30% noncarriers. ARIA occurred in 55% of homozygotes (vs 22% on placebo), 36% of heterozygotes (vs 13%) and 25% of noncarriers (vs 12%). Symptomatic ARIA-E occurred in 8%, 7% and 4% of those groups, and serious ARIA in 3%, 2% and 1%. The label states that “an FDA-authorized test for detection of ApoE ε4 alleles to identify patients at risk of ARIA … is not currently available” and that tests in use “may vary in accuracy and design.”

Other risk factors the label names. MRI findings that may indicate cerebral amyloid angiopathy (amyloid in the walls of brain blood vessels) — in the trial, at least 2 microhemorrhages or at least 1 area of superficial siderosis at baseline — were identified as risk factors for ARIA. The label also reports one fatal brain hemorrhage in a donanemab patient who had focal neurologic symptoms of ARIA and received a clot-dissolving drug, and it calls for caution with anticoagulant and thrombolytic medicines in people already receiving donanemab.

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8. Other Warnings and Side Effects

• Infusion-related reactions: the CDER notice lists flu-like symptoms, nausea, vomiting and changes in blood pressure. The label reports them in 9% of donanemab patients vs 0.5% on placebo, mostly within the first 4 infusions, and mostly mild or moderate; they led 4% of donanemab patients to stop treatment.
• Hypersensitivity reactions: the notice names anaphylaxis (a severe, life-threatening allergic reaction) and angioedema (swelling). The label lists known serious hypersensitivity to the drug or its ingredients as its one contraindication.
• Most common side effects: the notice names ARIA and headache. The label’s highlights list ARIA-E, ARIA-H microhemorrhage, ARIA-H superficial siderosis and headache as the reactions seen in at least 10% of patients and more often than with placebo.
• Stopping for side effects: 13% of donanemab patients vs 4% on placebo stopped study treatment because of an adverse reaction, per the label.
• Deaths: the published trial report states that three deaths in the donanemab group and one in the placebo group were considered treatment related.

Decisions about any medicine belong with a clinician who knows the person’s full history, scans and other prescriptions.

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9. What the Approval Does Not Do

• It does not cover moderate or severe dementia. The label ties treatment start to mild cognitive impairment or mild dementia, the stages studied.
• It does not cure or reverse Alzheimer’s disease. Patients on the drug still declined on every scale; the measured effect is a slower rate of decline than on placebo.
• It does not cover people without confirmed amyloid. Amyloid pathology is to be confirmed before treatment.
• It does not establish longer-term benefit. The label states there is no data beyond 76 weeks to show whether further dosing is needed for longer-term clinical benefit.
• It does not come with an FDA-authorized ApoE ε4 test. The label says none was available.

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10. The July 2025 Label Revision

The prescribing information was revised in July 2025 (supplement 4 to BLA 761248). Its “Recent Major Changes” box lists the Boxed Warning, Dosage and Administration (sections 2.2 to 2.5) and Warnings and Precautions (sections 5.1 and 5.3), each dated 7/2025.

Boxed warning changes. In the 2025 version the sentence on serious events no longer says “rarely,” and a new sentence follows it. The revised text reads: “ARIA usually occurs early in treatment and is usually asymptomatic, although serious and life-threatening events can occur. ARIA can be fatal.” The sentence on talking with patients before genetic testing was reworded to: “Prior to testing, the risk of ARIA across genotypes and the implications of genetic testing results should be discussed with patients.” The rest of the boxed warning is unchanged. (The 2024 Medication Guide for patients already stated that “ARIA can be fatal.”)

New starting schedule. The 2025 label replaces the trial’s starting schedule with a gradual increase over the first three infusions, every four weeks: 350 mg, then 700 mg, then 1,050 mg, then 1,400 mg from the fourth infusion on. The label bases this on a second randomized trial (Study 2, published as TRAILBLAZER-ALZ 6), which compared dosing regimens and found that this one gave “comparable pharmacodynamic effects on amyloid plaque reduction with a reduced incidence of ARIA-related events.” On that schedule (212 patients), the label reports ARIA in 29%, ARIA-E in 16% and ARIA-H in 25% of patients, and symptomatic ARIA-E in 3% through 12 months of treatment; brain hemorrhage larger than 1 cm was reported in 1% of patients treated in Study 2. One fatal brain hemorrhage in Study 2 occurred in the setting of ARIA and a clot-dissolving drug.

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11. Dates and Status as of 11 October 2026

• 7 March 2013: the investigational new drug application (the exemption that permits testing in people) became effective, per the FDA’s 2025 patent-term notice.
• 18 May 2022: the FDA’s records date the complete biologics license application to this day. The same notice records that the applicant claimed an earlier date of 3 September 2021, and that the FDA did not accept it.
• 10 June 2024: the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee met to discuss the application (see section 12).
• 2 July 2024: FDA approval.
• July 2025: label revised (boxed warning, dosing, warnings).
• 14 July 2025: the FDA published its regulatory review period determination for patent-extension purposes.

Status as of 11 October 2026: approved; final action, with the label as revised in July 2025. A check of the Federal Register through 11 October 2026 found no FDA document withdrawing the approval or changing the indication. The documents found that mention the drug are the 2024 advisory-committee meeting notice, the 2025 patent-term notice, and a July 2026 notice reestablishing the advisory committee that lists the June 2024 meeting.

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12. How the Approval Fits the FDA’s Other Steps

2024: the advisory committee meeting. On 8 May 2024 the FDA announced in the Federal Register (89 FR 38902, Docket No. FDA-2024-N-1869) that its Peripheral and Central Nervous System Drugs Advisory Committee would meet on 10 June 2024 to discuss biologics license application 761248 for donanemab “for the treatment of early symptomatic Alzheimer’s disease,” and opened a public docket for comments. An advisory committee gives the FDA outside advice; the notice describes the committee’s general function as providing “advice and recommendations to FDA on regulatory issues.” The committee’s vote is not reported on this page because the meeting record was not among the documents reviewed. A July 2026 Federal Register notice (91 FR 46444) lists this as the committee’s only meeting in 2024.

A class of medicines. The boxed warning speaks of “monoclonal antibodies directed against aggregated forms of beta amyloid” as a group and of serious brain hemorrhages “observed in patients treated with this class of medications.” The ARIA warning is therefore written as a class warning, not only a donanemab finding. A related antibody of the same class, lecanemab, is described in a published trial listed under Key Research Papers.

2025: patent-term review. On 14 July 2025 the FDA published its determination of the drug’s regulatory review period (90 FR 31210, Docket No. FDA-2024-E-5009): 4,137 days in total, 3,360 days of testing and 777 days of FDA review. The notice explains that this sets the maximum possible patent extension, which the U.S. Patent and Trademark Office then limits by statute; the applicant sought 1,827 days.

2025: label revision. The July 2025 revision strengthened the boxed warning’s wording and changed the starting dose schedule (section 10).

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13. Primary Documents

1. U.S. Food and Drug Administration, CDER (2024). FDA approves treatment for adults with Alzheimer’s disease. News & Events for Human Drugs, content current as of 2 July 2024 — fda.gov CDER notice
2. U.S. Food and Drug Administration, CDER. Novel Drug Approvals for 2024 (entry 22, 7/2/2024) — fda.gov Novel Drug Approvals for 2024
3. Prescribing information for donanemab-azbt injection, BLA 761248, as approved (revised 7/2024) — accessdata.fda.gov label (2024, PDF)
4. Prescribing information for donanemab-azbt injection, BLA 761248 supplement 4 (revised 7/2025) — accessdata.fda.gov label (2025, PDF)
5. Food and Drug Administration, HHS (2024). Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting; Establishment of a Public Docket; Request for Comments (Biologics License Application 761248, for donanemab solution for intravenous infusion). Federal Register 89 FR 38902, 8 May 2024. Docket No. FDA-2024-N-1869 — FR Doc. 2024-10051
6. Food and Drug Administration, HHS (2025). Determination of Regulatory Review Period for Purposes of Patent Extension (donanemab-azbt; product name omitted here). Federal Register 90 FR 31210–31211, 14 July 2025. Docket No. FDA-2024-E-5009 — FR Doc. 2025-13044
7. Food and Drug Administration, HHS (2026). Advisory Committee; Peripheral and Central Nervous System Drugs Advisory Committee; Termination and Reestablishment. Federal Register 91 FR 46444, 23 July 2026. Docket No. FDA-2026-N-0008 — FR Doc. 2026-14829

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Key Research Papers

1. Mintun MA, Lo AC, Duggan Evans C, Wessels AM, Ardayfio PA, Andersen SW, Shcherbinin S, Sparks J, Sims JR, Brys M, Apostolova LG, Salloway SP, Skovronsky DM (2021). Donanemab in Early Alzheimer’s Disease. New England Journal of Medicine 384(18):1691-1704. The phase 2 trial, using the same 700 mg then 1,400 mg schedule every 4 weeks for up to 72 weeks — PubMed PMID: 33720637
2. Sims JR, Zimmer JA, Evans CD, Lu M, Ardayfio P, Sparks J, Wessels AM, Shcherbinin S, Wang H, Monkul Nery ES, Collins EC, Solomon P, Salloway S, Apostolova LG, Hansson O, Ritchie C, Brooks DA, Mintun M, Skovronsky DM; TRAILBLAZER-ALZ 2 Investigators (2023). Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial. JAMA 330(6):512-527. The 1,736-person phase 3 trial (Study 1 in the label) behind the approval — PubMed PMID: 37459141
3. Wang H, Serap Monkul Nery E, Ardayfio P, Khanna R, Otero Svaldi D, Gueorguieva I, Shcherbinin S, Andersen SW, Hauck PM, Engle SE, Brooks DA, Collins EC, et al. (2025). Modified titration of donanemab reduces ARIA risk and maintains amyloid reduction. Alzheimer’s & Dementia 21(4):e70062. TRAILBLAZER-ALZ 6, the dosing study behind the 2025 label change; ARIA-E at 24 weeks was 13.7% with the gradual schedule vs 23.7% with the standard schedule (a correction to this article was published in the same journal in August 2025) — PubMed PMID: 40172303
4. Rabinovici GD, Selkoe DJ, Schindler SE, Aisen P, Apostolova LG, Atri A, Greenberg SM, Hendrix SB, Petersen RC, Weiner M, Salloway S, Cummings J (2025). Donanemab: Appropriate use recommendations. Journal of Prevention of Alzheimer’s Disease 12(5):100150. Expert-workgroup consensus on patient selection, ApoE genotyping and MRI monitoring — PubMed PMID: 40155270
5. Hampel H, Elhage A, Cho M, Apostolova LG, Nicoll JAR, Atri A (2023). Amyloid-related imaging abnormalities (ARIA): radiological, biological and clinical characteristics. Brain 146(11):4414-4424. A review of what ARIA-E and ARIA-H are, how they are detected and their risk factors — PubMed PMID: 37280110
6. van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, Chen C, Gee M, Kanekiyo M, Li D, Reyderman L, Cohen S, Froelich L, Katayama S, et al. (2023). Lecanemab in Early Alzheimer’s Disease. New England Journal of Medicine 388(1):9-21. The phase 3 trial of another anti-amyloid antibody in the same class, in 1,795 people with early Alzheimer’s disease — PubMed PMID: 36449413

PubMed Topic Searches

1. PubMed: donanemab
2. PubMed: amyloid-related imaging abnormalities (ARIA)
3. PubMed: anti-amyloid antibodies in early Alzheimer’s disease

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Connections

• FDA Actions of 2024
• FDA and Regulation
• Resmetirom for Fatty-Liver Scarring (2024)
• Xanomeline-Trospium for Schizophrenia (2024)
• MDMA for PTSD Not Approved (2024)
• Laboratory-Developed Tests Rule (2024)
• Alzheimer’s Disease
• Alzheimer’s Disease: History and Discovery
• IDOL Enzyme and Alzheimer’s Disease
• Brain Aging
• Dementia

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