Kisunla

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.

KIS-0001-MG-20240702

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.

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.

Safety and effectiveness in pediatric patients have not been established.

In Study 1, the age of patients exposed to KISUNLA ranged from 59 to 86 years, with a mean age of 73 years; 90% were 65 years and older, and 41% were 75 years and older. No overall differences in safety or effectiveness of KISUNLA have been observed between patients 65 years of age and older and younger adult patients.

In Study 2, the range of patients exposed to KISUNLA ranged from 59 to 85 years, with mean age of 74 years; 93% were 65 years and older, 55% were 75 years and older. Study 2 did not include a sufficient number of younger adult patients to determine if patients 65 years of age and older respond differently than younger adult patients.

The observed incidence of anti-drug antibodies (ADA) is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of ADA in the studies described below with the incidence of ADAs in other studies, including those of donanemab-azbt or of other donanemab products.

In up to 18 months of treatment in Study 1 [see Clinical Studies (14)], 87% (691/792) of patients receiving KISUNLA Dosing Regimen 1 developed anti-donanemab-azbt antibodies, and of those, 100% had neutralizing antibodies. In up to 12 months of treatment in Study 2, 87% (176/202) of patients receiving KISUNLA Dosing Regimen 2 developed anti-donanemab-azbt antibodies, and of those, 100% had neutralizing antibodies.

Anti-donanemab-azbt antibody formation was associated with a higher incidence of infusion-related reactions compared to placebo [see Adverse Reactions (6.1)].

The effectiveness of KISUNLA for the treatment of Alzheimer's disease was established by Study 1, which assessed Dosing Regimen 1 (700 mg every 4 weeks for the first 3 doses, and then 1,400 mg every 4 weeks). Study 2 was conducted to assess different titration regimens, including Dosing Regimen 2 (doses every 4 weeks with 350 mg the first infusion, 700 mg the second infusion, 1,050 mg the third infusion, and then 1,400 mg every 4 weeks) that demonstrated comparable pharmacodynamic effects on amyloid plaque reduction with a reduced incidence of ARIA-related events compared to Dosing Regimen 1 [see Dosage and Administration (2.2), Warnings and Precautions (5.1), Clinical Pharmacology (12.2)].

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)].

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)]

The pharmacokinetics (PK) of KISUNLA were characterized using a population PK analysis with concentration data collected from 2131 patients with Alzheimer's disease who received KISUNLA in single or multiple doses. Accumulation of <1.3-fold occurs with every-4-week dosing. Steady-state exposures, which were similar from Dosing Regimens 1 and 2, are achieved after a single dose. In single doses from 350 to 2800 mg (~2 times the approved recommended dosage of 1,400 mg), and multiple 350 to 1,400 mg doses, exposures (C_max and AUC) increased proportionally.

Confirm the presence of amyloid beta pathology prior to initiating treatment [see Clinical Pharmacology (12.1)].

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.

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).

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.

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, as evaluated in Study 1 [see Clinical Studies (14)].

• Prior to administration, KISUNLA must be diluted with 0.9% sodium chloride injection (see Table 4 ).
• Use aseptic technique when preparing the diluted KISUNLA solution for intravenous infusion.
• Allow KISUNLA to equilibrate to room temperature before preparation.
• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. KISUNLA solution is clear to opalescent, colorless to slightly yellow to slightly brown. Do not use if particulate matter or discolorations are present.
• Withdraw required volume of KISUNLA and mix with 0.9% sodium chloride injection, to the recommended total volume for a final concentration of 4 mg/mL to 10 mg/mL (see Table 4 ). Use only 0.9% sodium chloride injection for dilution.

• Each vial is for one-time use only. Discard any unused portion left in the vial.
• Gently invert the diluted KISUNLA solution to mix completely. Do not shake.
• After dilution, immediate use is recommended [see Description (11)]. If the diluted KISUNLA solution is not administered immediately, store refrigerated at 2°C to 8°C (36°F to 46°F) for up to 72 hours or at room temperature (20°C to 25°C [68°F to 77°F]) for up to 12 hours.
• Do not freeze the diluted KISUNLA solution.
• Storage times include the duration of infusion.

• Amyloid Related Imaging Abnormalities (ARIA): Enhanced clinical vigilance for ARIA is recommended during the first 24 weeks of treatment with KISUNLA. Risk of ARIA, including symptomatic ARIA, was increased in apolipoprotein E ε4 (ApoE ε4) homozygotes compared to heterozygotes and noncarriers. The risk of ARIA-E and ARIA-H is increased in KISUNLA-treated patients with pretreatment microhemorrhages and/or superficial siderosis. If a patient experiences symptoms suggestive of ARIA, clinical evaluation should be performed, including MRI scanning if indicated. (2.3, 5.1)
• Infusion-Related Reactions: The infusion rate may be reduced, or the infusion may be discontinued, and appropriate therapy initiated as clinically indicated. Consider pre-treatment with antihistamines, acetaminophen, or corticosteroids prior to subsequent dosing. (5.3)

• 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)

Injection: 350 mg/20 mL (17.5 mg/mL) clear to opalescent, colorless to slightly yellow to slightly brown solution in a single-dose vial.

Hypersensitivity reactions, including anaphylaxis and angioedema, have occurred in patients who were treated with KISUNLA [see Adverse Reactions (6.1)]. Promptly discontinue the infusion upon the first observation of any signs or symptoms consistent with a hypersensitivity reaction and initiate appropriate therapy. KISUNLA is contraindicated in patients with a history of serious hypersensitivity to donanemab-azbt or to any of the excipients of KISUNLA.

In Study 1, infusion-related reactions were observed in 9% of patients treated with KISUNLA, the majority (70%) of which occurred within the first 4 infusions, compared to 0.5% of patients on placebo. Infusion-related reactions were mostly mild (57%) or moderate (39%) in severity. Infusion-related reactions resulted in discontinuations in 4% of patients treated with KISUNLA.

In Study 2, infusion-related reactions associated with KISUNLA occurred in 16% of patients; the majority (88%) occurred within the first 4 infusions. Infusion-related reactions were mostly mild (47%) or moderate (50%) in severity. Infusion-related reactions resulted in discontinuations in 2.8% of patients treated with KISUNLA.

Most infusion-related reactions associated with KISUNLA occurred during the infusion or within 30 minutes after completion of the infusion, however some have occurred hours after an infusion. Signs and symptoms of infusion-related reactions include chills, erythema, nausea/vomiting, flushing, difficulty breathing/dyspnea, sweating, elevated blood pressure, headache, chest pain, and low blood pressure.

In the event of an infusion-related reaction, the infusion rate may be reduced, or the infusion may be discontinued, and appropriate therapy initiated as clinically indicated. Consider pre-treatment with antihistamines, acetaminophen, or corticosteroids prior to subsequent dosing.

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.

• Visually inspect the diluted KISUNLA solution for particles or discoloration prior to administration. Do not use if it is discolored, or opaque or foreign particles are seen.
• Prior to infusion, if the diluted solution has been stored under refrigeration, allow the diluted KISUNLA solution to warm to room temperature.
• Administer the entire diluted solution intravenously over approximately 30 minutes.
• Flush the line only with 0.9% sodium chloride injection at the end of the infusion per access specific line maintenance protocol.
• Observe the patient post-infusion for a minimum of 30 minutes, and consider longer periods of observation if clinically indicated, to evaluate for infusion reactions and hypersensitivity reactions. The infusion rate may be reduced, or the infusion may be discontinued, and appropriate therapy administered as clinically indicated. Consider pre-medication at subsequent dosing with antihistamines, non-steroidal anti-inflammatory drugs, or corticosteroids [see Warnings and Precautions (5.2)].

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Product of Ireland or South Korea

NDC 0002-9401-01

Rx only

kisunla^TM

(donanemab-azbt)

injection

350 mg/20 mL

(17.5 mg/mL)

For Intravenous Infusion Only

Must Dilute Prior to Use

One Single-Dose Vial

Dispense with enclosed Medication Guide

www.kisunla.com

Lilly

Product of Ireland

Product of South Korea

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), which can be observed on MRI as brain edema or sulcal effusions, and ARIA with hemosiderin deposition (ARIA-H), which includes microhemorrhage and superficial siderosis. ARIA can occur spontaneously in patients with Alzheimer's disease, particularly in patients with MRI findings suggestive of cerebral amyloid angiopathy, such as pretreatment microhemorrhage or superficial siderosis. ARIA-H associated with monoclonal antibodies directed against aggregated forms of beta amyloid generally occurs in association with an occurrence of ARIA-E. ARIA-H of any cause and ARIA-E can occur together.

ARIA usually occurs early in treatment and is usually asymptomatic, although serious and life-threatening events, including seizure and status epilepticus, can occur. ARIA can be fatal. When present, reported symptoms associated with ARIA may include, but are not limited to, headache, confusion, visual changes, dizziness, nausea, and gait difficulty. Focal neurologic deficits may also occur. Symptoms associated with ARIA usually resolve over time. In addition to ARIA, intracerebral hemorrhages greater than 1 cm in diameter have occurred in patients treated with KISUNLA.

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.

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)] .

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.

KIS-0001-MG-20240702

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.

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.

Safety and effectiveness in pediatric patients have not been established.

In Study 1, the age of patients exposed to KISUNLA ranged from 59 to 86 years, with a mean age of 73 years; 90% were 65 years and older, and 41% were 75 years and older. No overall differences in safety or effectiveness of KISUNLA have been observed between patients 65 years of age and older and younger adult patients.

In Study 2, the range of patients exposed to KISUNLA ranged from 59 to 85 years, with mean age of 74 years; 93% were 65 years and older, 55% were 75 years and older. Study 2 did not include a sufficient number of younger adult patients to determine if patients 65 years of age and older respond differently than younger adult patients.

The observed incidence of anti-drug antibodies (ADA) is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of ADA in the studies described below with the incidence of ADAs in other studies, including those of donanemab-azbt or of other donanemab products.

In up to 18 months of treatment in Study 1 [see Clinical Studies (14)], 87% (691/792) of patients receiving KISUNLA Dosing Regimen 1 developed anti-donanemab-azbt antibodies, and of those, 100% had neutralizing antibodies. In up to 12 months of treatment in Study 2, 87% (176/202) of patients receiving KISUNLA Dosing Regimen 2 developed anti-donanemab-azbt antibodies, and of those, 100% had neutralizing antibodies.

Anti-donanemab-azbt antibody formation was associated with a higher incidence of infusion-related reactions compared to placebo [see Adverse Reactions (6.1)].

The effectiveness of KISUNLA for the treatment of Alzheimer's disease was established by Study 1, which assessed Dosing Regimen 1 (700 mg every 4 weeks for the first 3 doses, and then 1,400 mg every 4 weeks). Study 2 was conducted to assess different titration regimens, including Dosing Regimen 2 (doses every 4 weeks with 350 mg the first infusion, 700 mg the second infusion, 1,050 mg the third infusion, and then 1,400 mg every 4 weeks) that demonstrated comparable pharmacodynamic effects on amyloid plaque reduction with a reduced incidence of ARIA-related events compared to Dosing Regimen 1 [see Dosage and Administration (2.2), Warnings and Precautions (5.1), Clinical Pharmacology (12.2)].

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)].

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)]

The pharmacokinetics (PK) of KISUNLA were characterized using a population PK analysis with concentration data collected from 2131 patients with Alzheimer's disease who received KISUNLA in single or multiple doses. Accumulation of <1.3-fold occurs with every-4-week dosing. Steady-state exposures, which were similar from Dosing Regimens 1 and 2, are achieved after a single dose. In single doses from 350 to 2800 mg (~2 times the approved recommended dosage of 1,400 mg), and multiple 350 to 1,400 mg doses, exposures (C_max and AUC) increased proportionally.

Confirm the presence of amyloid beta pathology prior to initiating treatment [see Clinical Pharmacology (12.1)].

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.

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).

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.

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, as evaluated in Study 1 [see Clinical Studies (14)].

• Prior to administration, KISUNLA must be diluted with 0.9% sodium chloride injection (see Table 4 ).
• Use aseptic technique when preparing the diluted KISUNLA solution for intravenous infusion.
• Allow KISUNLA to equilibrate to room temperature before preparation.
• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. KISUNLA solution is clear to opalescent, colorless to slightly yellow to slightly brown. Do not use if particulate matter or discolorations are present.
• Withdraw required volume of KISUNLA and mix with 0.9% sodium chloride injection, to the recommended total volume for a final concentration of 4 mg/mL to 10 mg/mL (see Table 4 ). Use only 0.9% sodium chloride injection for dilution.

• Each vial is for one-time use only. Discard any unused portion left in the vial.
• Gently invert the diluted KISUNLA solution to mix completely. Do not shake.
• After dilution, immediate use is recommended [see Description (11)]. If the diluted KISUNLA solution is not administered immediately, store refrigerated at 2°C to 8°C (36°F to 46°F) for up to 72 hours or at room temperature (20°C to 25°C [68°F to 77°F]) for up to 12 hours.
• Do not freeze the diluted KISUNLA solution.
• Storage times include the duration of infusion.

• Amyloid Related Imaging Abnormalities (ARIA): Enhanced clinical vigilance for ARIA is recommended during the first 24 weeks of treatment with KISUNLA. Risk of ARIA, including symptomatic ARIA, was increased in apolipoprotein E ε4 (ApoE ε4) homozygotes compared to heterozygotes and noncarriers. The risk of ARIA-E and ARIA-H is increased in KISUNLA-treated patients with pretreatment microhemorrhages and/or superficial siderosis. If a patient experiences symptoms suggestive of ARIA, clinical evaluation should be performed, including MRI scanning if indicated. (2.3, 5.1)
• Infusion-Related Reactions: The infusion rate may be reduced, or the infusion may be discontinued, and appropriate therapy initiated as clinically indicated. Consider pre-treatment with antihistamines, acetaminophen, or corticosteroids prior to subsequent dosing. (5.3)

• 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)

Injection: 350 mg/20 mL (17.5 mg/mL) clear to opalescent, colorless to slightly yellow to slightly brown solution in a single-dose vial.

Hypersensitivity reactions, including anaphylaxis and angioedema, have occurred in patients who were treated with KISUNLA [see Adverse Reactions (6.1)]. Promptly discontinue the infusion upon the first observation of any signs or symptoms consistent with a hypersensitivity reaction and initiate appropriate therapy. KISUNLA is contraindicated in patients with a history of serious hypersensitivity to donanemab-azbt or to any of the excipients of KISUNLA.

In Study 1, infusion-related reactions were observed in 9% of patients treated with KISUNLA, the majority (70%) of which occurred within the first 4 infusions, compared to 0.5% of patients on placebo. Infusion-related reactions were mostly mild (57%) or moderate (39%) in severity. Infusion-related reactions resulted in discontinuations in 4% of patients treated with KISUNLA.

In Study 2, infusion-related reactions associated with KISUNLA occurred in 16% of patients; the majority (88%) occurred within the first 4 infusions. Infusion-related reactions were mostly mild (47%) or moderate (50%) in severity. Infusion-related reactions resulted in discontinuations in 2.8% of patients treated with KISUNLA.

Most infusion-related reactions associated with KISUNLA occurred during the infusion or within 30 minutes after completion of the infusion, however some have occurred hours after an infusion. Signs and symptoms of infusion-related reactions include chills, erythema, nausea/vomiting, flushing, difficulty breathing/dyspnea, sweating, elevated blood pressure, headache, chest pain, and low blood pressure.

In the event of an infusion-related reaction, the infusion rate may be reduced, or the infusion may be discontinued, and appropriate therapy initiated as clinically indicated. Consider pre-treatment with antihistamines, acetaminophen, or corticosteroids prior to subsequent dosing.

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.

• Visually inspect the diluted KISUNLA solution for particles or discoloration prior to administration. Do not use if it is discolored, or opaque or foreign particles are seen.
• Prior to infusion, if the diluted solution has been stored under refrigeration, allow the diluted KISUNLA solution to warm to room temperature.
• Administer the entire diluted solution intravenously over approximately 30 minutes.
• Flush the line only with 0.9% sodium chloride injection at the end of the infusion per access specific line maintenance protocol.
• Observe the patient post-infusion for a minimum of 30 minutes, and consider longer periods of observation if clinically indicated, to evaluate for infusion reactions and hypersensitivity reactions. The infusion rate may be reduced, or the infusion may be discontinued, and appropriate therapy administered as clinically indicated. Consider pre-medication at subsequent dosing with antihistamines, non-steroidal anti-inflammatory drugs, or corticosteroids [see Warnings and Precautions (5.2)].

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Product of Ireland or South Korea

NDC 0002-9401-01

Rx only

kisunla^TM

(donanemab-azbt)

injection

350 mg/20 mL

(17.5 mg/mL)

For Intravenous Infusion Only

Must Dilute Prior to Use

One Single-Dose Vial

Dispense with enclosed Medication Guide

www.kisunla.com

Lilly

Product of Ireland

Product of South Korea

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), which can be observed on MRI as brain edema or sulcal effusions, and ARIA with hemosiderin deposition (ARIA-H), which includes microhemorrhage and superficial siderosis. ARIA can occur spontaneously in patients with Alzheimer's disease, particularly in patients with MRI findings suggestive of cerebral amyloid angiopathy, such as pretreatment microhemorrhage or superficial siderosis. ARIA-H associated with monoclonal antibodies directed against aggregated forms of beta amyloid generally occurs in association with an occurrence of ARIA-E. ARIA-H of any cause and ARIA-E can occur together.

ARIA usually occurs early in treatment and is usually asymptomatic, although serious and life-threatening events, including seizure and status epilepticus, can occur. ARIA can be fatal. When present, reported symptoms associated with ARIA may include, but are not limited to, headache, confusion, visual changes, dizziness, nausea, and gait difficulty. Focal neurologic deficits may also occur. Symptoms associated with ARIA usually resolve over time. In addition to ARIA, intracerebral hemorrhages greater than 1 cm in diameter have occurred in patients treated with KISUNLA.

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.

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)] .

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)].