Donanemab-Azbt
FDA Drug Information • Also known as: Kisunla
- Brand Names
- Kisunla
- Route
- INTRAVENOUS
- Dosage Form
- INJECTION, SOLUTION
- Product Type
- HUMAN PRESCRIPTION DRUG
⚠ Boxed Warning (Black Box)
WARNING: AMYLOID RELATED IMAGING ABNORMALITIES Monoclonal antibodies directed against aggregated forms of beta amyloid, including KISUNLA, 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 can occur. ARIA can be fatal. 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 KISUNLA [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 KISUNLA, 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, the risk of ARIA across genotypes and the implications of genetic testing results should be discussed with patients. Prescribers should inform patients that if genotype testing is not performed, they can still be treated with KISUNLA; 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 KISUNLA for the treatment of Alzheimer's disease and potential risk of serious adverse events associated with ARIA when deciding to initiate treatment with KISUNLA [see Warnings and Precautions ( 5.1 ) and Clinical Studies ( 14 )] . WARNING: AMYLOID RELATED IMAGING ABNORMALITIES See full prescribing information for complete boxed warning. Monoclonal antibodies directed against aggregated forms of beta amyloid, including KISUNLA, can cause amyloid related imaging abnormalities (ARIA), as ARIA with edema (ARIA-E) and ARIA with hemosiderin deposition (ARIA-H). ARIA is usually asymptomatic, although serious and life-threatening events can occur. ARIA can be fatal. Serious intracerebral hemorrhages >1 cm have occurred in patients treated with this class of medications. ARIA-E can cause focal neurologic deficits that can mimic ischemic stroke. ( 5.1 , 6.1 ) ApoE ε4 Homozygotes Patients treated with this class of medications, including KISUNLA, who are ApoE ε4 homozygotes have a higher incidence of ARIA, including symptomatic and serious ARIA, compared to heterozygotes and noncarriers. Testing for ApoE ε 4 status should be performed prior to initiation of treatment to inform the risk of developing ARIA. Prior to testing, the risk of ARIA across genotypes and implications of genetic testing results should be discussed with patients. ( 5.1 ) Consider the benefit for the treatment of Alzheimer's disease and risk of ARIA when deciding to treat with KISUNLA. ( 5.1 , 14 )
Description
11 DESCRIPTION Donanemab-azbt is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against insoluble N-truncated pyroglutamate amyloid beta, and is expressed in a Chinese hamster ovary cell line. Donanemab-azbt has an approximate molecular weight of 145 kDa. KISUNLA (donanemab-azbt) injection is a sterile, preservative-free, clear to opalescent, colorless to slightly yellow to slightly brown solution for intravenous infusion after dilution. KISUNLA is supplied in single-dose vials available in a concentration of 350 mg/20 mL (17.5 mg/mL). Each mL of solution contains 17.5 mg donanemab-azbt, anhydrous citric acid (0.32 mg), polysorbate 80 (0.20 mg), sodium citrate (2.15 mg), sucrose (80 mg), and Water for Injection, USP, at a pH of 5.5 to 6.5.
What Is Donanemab-Azbt Used For?
1 INDICATIONS AND USAGE KISUNLA TM is indicated for the treatment of Alzheimer's disease. Treatment with KISUNLA 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. KISUNLA is an amyloid beta-directed antibody indicated for the treatment of Alzheimer's disease. Treatment with KISUNLA 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. ( 1 )
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Confirm the presence of amyloid beta pathology prior to initiating treatment. ( 2.1 ) Administer KISUNLA as an intravenous infusion over approximately 30 minutes every four weeks as follows ( 2.2 ): Infusion 1: 350 mg Infusion 2: 700 mg Infusion 3: 1,050 mg Infusion 4 and beyond: 1,400 mg Consider stopping dosing with KISUNLA based on reduction of amyloid plaques to minimal levels on amyloid PET imaging. ( 2.2 ) Obtain a recent baseline brain MRI prior to initiating treatment. ( 2.3 , 5.1 ) Obtain an MRI prior to the 2nd, 3rd, 4th, and 7th infusions. If radiographically observed ARIA occurs, treatment recommendations are based on type, severity, and presence of symptoms. ( 2.3 , 5.1 ) Dilution to a final concentration of 4 mg/mL to 10 mg/mL with 0.9% Sodium Chloride Injection, is required prior to administration. ( 2.4 ) 2.1 Patient Selection Confirm the presence of amyloid beta pathology prior to initiating treatment [see Clinical Pharmacology ( 12.1 )] . 2.2 Dosing Instructions Administer KISUNLA every four weeks as an intravenous infusion over approximately 30 minutes with the recommended dosage and dosing schedule described in Table 1 . KISUNLA must be diluted prior to administration ( see Table 4 ). Table 1: Recommended Dosage* and Dosing Schedule *Dosing Regimen 2 [see Warnings and Precautions ( 5.1 ) and Clinical Studies ( 14 )] Intravenous Infusion (every 4 weeks) KISUNLA Dosage (administered over approximately 30 minutes) Infusion 1 350 mg Infusion 2 700 mg Infusion 3 1,050 mg Infusion 4 and beyond 1,400 mg Consider stopping dosing with KISUNLA based on reduction of amyloid plaques to minimal levels on amyloid PET imaging. In Study 1 and Study 2, dosing was stopped based on a reduction of amyloid levels below predefined thresholds on PET imaging [see Clinical Studies ( 14 )] . If an infusion is missed, resume administration every 4 weeks at the same dose as soon as possible. 2.3 Monitoring and Dosing Interruption for Amyloid Related Imaging Abnormalities KISUNLA can cause amyloid related imaging abnormalities -edema (ARIA-E) and -hemosiderin deposition (ARIA-H) [see Warnings and Precautions ( 5.1 ) and Adverse Reactions ( 6.1 )] . Monitoring for ARIA Obtain a recent baseline brain magnetic resonance imaging (MRI) prior to initiating treatment with KISUNLA. Obtain an MRI prior to the 2 nd , 3 rd , 4 th , and 7 th infusions. If a patient experiences symptoms suggestive of ARIA, clinical evaluation should be performed, including an MRI if indicated. Recommendations for Dosing Interruptions in Patients with ARIA ARIA-E The recommendations for dosing interruptions for patients with ARIA-E are provided in Table 2 . Table 2: Dosing Recommendations for Patients With ARIA-E c a Mild: discomfort noticed, but no disruption of normal daily activity. Moderate: discomfort sufficient to reduce or affect normal daily activity. Severe: incapacitating, with inability to work or to perform normal daily activity. b Suspend until...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Amyloid Related Imaging Abnormalities [see Warnings and Precautions ( 5.1 )] Hypersensitivity Reactions [see Warnings and Precautions ( 5.2 )] Infusion-Related Reactions [see Warnings and Precautions ( 5.3 )] Most common adverse reactions (at least 10% and higher incidence compared to placebo): ARIA-E, ARIA-H microhemorrhage, ARIA-H superficial siderosis, and headache. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Dosing Regimen and Safety A lower incidence of ARIA occurred with the dosing regimen administered in Study 2 (350 mg/700 mg/1,050 mg/1,400 mg; Dosing Regimen 2) as compared to the regimen administered in Study 1 (700 mg/700 mg/700 mg/1,400 mg; Dosing Regimen 1); therefore, Dosing Regimen 2 is recommended for administration of KISUNLA [see Dosage and Administration ( 2.2 ), Warnings and Precautions ( 5.1 ), Clinical Pharmacology ( 12.2 ), Clinical Studies ( 14 )] . The safety of KISUNLA has been evaluated in 3727 patients with Alzheimer's disease who received at least one dose of KISUNLA intravenously. In the other clinical studies of KISUNLA, 1912 patients with Alzheimer's disease received KISUNLA once monthly for at least 6 months, 1057 patients for at least 12 months, and 432 patients for at least 18 months, at the Dosing Regimen 1. Study 1 In Study 1 (NCT04437511), a total of 853 patients with Alzheimer's disease received at least one dose of KISUNLA; patients were randomized to receive KISUNLA Dosing Regimen 1 or placebo. Thirteen percent of patients treated with KISUNLA compared to 4% of patients on placebo stopped study treatment because of an adverse reaction. The most common adverse reaction leading to discontinuation of KISUNLA was infusion-related reaction (4% of patients treated with KISUNLA compared to no patient on placebo). Table 7 shows adverse reactions that were reported in at least 5% of patients treated with KISUNLA and at least 2% more frequently than in patients on placebo in Study 1. Table 7: Adverse Reactions Reported in at Least 5% of Patients Treated With KISUNLA and at Least 2% Higher Than Placebo in Study 1 a Administered as a different titration regimen (700 mg/700 mg/700 mg/1,400 mg) than the currently recommended dosing regimen (350 mg/700 mg/1,050 mg/1,400 mg) b As assessed by MRI. A participant could have both microhemorrhage and superficial siderosis. Adverse Reaction KISUNLA a N = 853 % Placebo N = 874 % ARIA-H microhemorrhage b 25 11 ARIA-E 24 2 ARIA-H superficial siderosis b 15 3 Headache 13 10 Infusion-related reaction 9 0.5 Study 2 In Study 2 (NCT05738486), a total of 842 patients received at least one dose of KISUNLA; 212 patients were randomized to receive KISUNLA Dosing Regimen 2. In Study 2, compared to the rates reported with Dosing Regimen 1, higher rates of hypersensitivity reactions (8% of patients treated with Dosing Regimen 2) and infusion-related reactions (16% of patients treated with Dosing Regimen 2), and a lower rate of ARIA-E (16% of patients treated with Dosing Regimen 2) were observed [see Warnings and Precautions ( 5.1 ) and Clinical Studies ( 14 )]. Less Common Adverse Reactions Hypersensitivity Reactions [see Warnings and Precautions ( 5.2 )] Hypersensitivity reactions, including anaphylaxis, occurred in 3% of patients treated with KISUNLA compared to 0.7% of patients on placebo in Study 1 and in 8% of patients treated with KISUNLA Dosing Regimen 2 in Study 2. Intestinal Obstruction and Intestinal Perforation Serious adverse reactions of...
Contraindications
4 CONTRAINDICATIONS KISUNLA is contraindicated in patients with known serious hypersensitivity to donanemab-azbt or to any of the excipients. Reactions have included anaphylaxis [see Warnings and Precautions ( 5.2 )] . KISUNLA is contraindicated in patients with known serious hypersensitivity to donanemab-azbt or to any of the excipients. ( 4 , 5.2 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary There are no adequate data on KISUNLA use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. No animal studies have been conducted to assess the potential reproductive or developmental toxicity of KISUNLA. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied KISUNLA (donanemab-azbt) injection is a sterile, preservative-free, clear to opalescent, colorless to slightly yellow to slightly brown solution. KISUNLA is supplied in one vial per carton as follows: 350 mg/20 mL (17.5 mg/mL) single-dose vial: NDC 0002-9401-01. 16.2 Storage and Handling Unopened Vial Store refrigerated at 2°C to 8°C (36°F to 46°F). Keep the vial in the outer carton to protect from light. Do not freeze or shake. If refrigeration is not available, may be stored at room temperature (20°C to 25°C [68°F to 77°F]) for up to 3 days. Diluted Solution For storage of the diluted infusion solution see Dosage and Administration ( 2.4 ) . 16.1 How Supplied KISUNLA (donanemab-azbt) injection is a sterile, preservative-free, clear to opalescent, colorless to slightly yellow to slightly brown solution. KISUNLA is supplied in one vial per carton as follows: 350 mg/20 mL (17.5 mg/mL) single-dose vial: NDC 0002-9401-01.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.