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Kisunla is a brand name for Donanemab. The medicine, its uses, side effects and dosage are the same regardless of brand.
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…
Verbatim from this product's FDA label. Tap a section to expand.
2 DOSAGE AND ADMINISTRATION Confirm the presence of amyloid beta pathology prior to initiating treatment. 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 ) Obtain a recent baseline brain MRI prior to initiating treatment. 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.
9% Sodium Chloride Injection, is required prior to administration. 1 )] . 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 ). 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.
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.
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. gov/medwatch. 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.
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.
5 WARNINGS AND PRECAUTIONS 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.
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.
1 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), 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.
4 CONTRAINDICATIONS KISUNLA is contraindicated in patients with known serious hypersensitivity to donanemab-azbt or to any of the excipients. 2 )] . KISUNLA is contraindicated in patients with known serious hypersensitivity to donanemab-azbt or to any of the excipients.
2 )
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b Suspend until MRI demonstrates radiographic resolution and symptoms, if present, resolve; consider a follow-up MRI to assess for resolution 2 to 4 months after initial identification. Resumption of dosing should be guided by clinical judgment.
1 )] . Clinical Symptom Severity a ARIA-E Severity on MRI Mild Moderate Severe Asymptomatic May continue dosing at current dose and schedule Suspend dosing b Suspend dosing b Mild May continue dosing based on clinical judgment Suspend dosing b Moderate or Severe Suspend dosing b ARIA-H The recommendations for dosing interruptions for patients with ARIA-H are provided in Table 3 .
Table 3:
Dosing Recommendations for Patients With ARIA-H c a Suspend until MRI demonstrates radiographic stabilization and symptoms, if present, resolve; resumption of dosing should be guided by clinical judgment; consider a follow-up MRI to assess for stabilization 2 to 4 months after initial identification.
b Suspend until MRI demonstrates radiographic stabilization and symptoms, if present, resolve. Use clinical judgment when considering whether to continue treatment or permanently discontinue KISUNLA. 1 )] . Clinical Symptom Severity ARIA-H Severity on MRI Mild Moderate Severe Asymptomatic May continue dosing at current dose and schedule Suspend dosing a Suspend dosing b Symptomatic Suspend dosing a Suspend dosing a In patients who develop intracerebral hemorrhage greater than 1 cm in diameter during treatment with KISUNLA, suspend dosing until MRI demonstrates radiographic stabilization and symptoms, if present, resolve.
Use clinical judgment when considering whether to continue treatment or permanently discontinue KISUNLA after radiographic stabilization and resolution of symptoms. 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. 9% sodium chloride injection, to the recommended total volume for a final concentration of 4 mg/mL to 10 mg/mL ( see Table 4 ). 9% sodium chloride injection for dilution.
5 mL (4 mg/mL) to 1,050 mg/105 mL (10 mg/mL) 1,400 mg 80 mL d 60 mL to 270 mL 140 mL to 350 mL 1,400 mg/350 mL (4 mg/mL) to 1,400 mg/140 mL (10 mg/mL) 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. 5 Administration Instructions 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. 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.
2 )] .
A participant could have both microhemorrhage and superficial siderosis. 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.
1 ) and Clinical Studies ( 14 )]. 7% of patients on placebo in Study 1 and in 8% of patients treated with KISUNLA Dosing Regimen 2 in Study 2. 5%) treated with KISUNLA Dosing Regimen 2 in Study 2. 1%) on placebo in Study 1. 6 )] Infusion-related reactions occurred more frequently in patients treated with KISUNLA who developed anti-drug antibodies (ADAs) compared to patients who did not develop ADAs (Study 1, Dosing Regimen 1: 10% compared to 2%; Study 2, Dosing Regimen 2: 20% compared to 8%).
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.
Study 1 and Study 2 Overview [see Clinical Studies ( 14 )] In Study 1, safety was assessed in patients who received KISUNLA Dosing Regimen 1 (n = 853) compared to those who received placebo (n = 874). In Study 2, the effect of different dosing regimens of KISUNLA on ARIA was assessed, including in patients who received KISUNLA Dosing Regimen 2 (n=212), which is the recommended dosage and described below.
Incidence of ARIA A lower incidence of ARIA was observed with Dosing Regimen 2 as compared to Dosing Regimen 1. Therefore, Dosing Regimen 2 is the recommended dosage for KISUNLA. 1 )] . Clinical symptoms associated with ARIA-E resolved in approximately 85% of those patients.
Including asymptomatic radiographic events, ARIA, ARIA-E, and ARIA-H were observed in 36%, 24%, and 31% of patients treated with KISUNLA, respectively, compared to 14%, 2%, and 13% of patients on placebo, respectively. , ARIA-H in patients who did not also experience ARIA-E) for KISUNLA compared to placebo.
1 )] . Clinical symptoms associated with ARIA-E resolved in approximately 67% of patients at 12 months. Including asymptomatic radiographic events, ARIA, ARIA-E, and ARIA-H were observed in 29%, 16%, and 25% of patients treated with KISUNLA.
2% of patients on placebo in Study 1, and in 1% of patients treated with KISUNLA in Study 2. Fatal events of intracerebral hemorrhage in patients taking KISUNLA have been observed. Risk Factors for ARIA and Intracerebral Hemorrhage ApoE ε4 Carrier Status The risk of ARIA, including symptomatic and serious ARIA, is increased in apolipoprotein E ε4 (ApoE ε4) homozygotes, which include approximately 15% of Alzheimer's disease patients.
In Study 1, of patients in the KISUNLA arm (n=850), 17% were ApoE ε4 homozygotes, 53% were heterozygotes, and 30% were noncarriers. The incidence of ARIA through 18 months was higher in ApoE ε4 homozygotes (55% on KISUNLA vs. 22% on placebo) than in heterozygotes (36% on KISUNLA vs.
13% on placebo) and noncarriers (25% on KISUNLA vs. 12% on placebo). Among patients treated with KISUNLA, symptomatic ARIA-E occurred in 8% of ApoE ε4 homozygotes compared with 7% of heterozygotes and 4% of noncarriers. Serious events of ARIA occurred in 3% of ApoE ε4 homozygotes, 2% of heterozygotes, and 1% of noncarriers.
In Study 2, of patients treated with KISUNLA Dosing Regimen 2 (n=211), 10% were ApoE ε4 homozygotes, 55% were heterozygotes, and 36% were noncarriers. Symptomatic ARIA-E occurred in 0% of ApoE ε4 homozygotes compared with 4% of heterozygotes and 3% of noncarriers.
The small number of events and limited exposure in the ApoE ε4 subgroups limit definitive conclusions about the risk of ARIA-E. 3 )] . 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 KISUNLA; however, it cannot be determined if they are ApoE ε4 homozygotes and at a higher risk for ARIA.
An FDA-authorized test for detection of ApoE ε4 alleles to identify patients at risk of ARIA if treated with KISUNLA is not currently available. Currently available tests used to identify ApoE ε4 alleles may vary in accuracy and design.
Radiographic Findings of Cerebral Amyloid Angiopathy (CAA) Neuroimaging findings that may indicate CAA include evidence of prior intracerebral hemorrhage, cerebral microhemorrhage, and cortical superficial siderosis. CAA has an increased risk for intracerebral hemorrhage.
The presence of an ApoE ε4 allele is also associated with cerebral amyloid angiopathy. In Study 1, the baseline presence of at least 2 microhemorrhages or the presence of at least 1 area of superficial siderosis on MRI, which may be suggestive of CAA, were identified as risk factors for ARIA.
Patients were excluded from enrollment in Study 1 for findings on neuroimaging of prior intracerebral hemorrhage greater than 1 cm in diameter, more than 4 microhemorrhages, more than 1 area of superficial siderosis, severe white matter disease, and vasogenic edema.
Concomitant Antithrombotic or Thrombolytic Medication In Study 1, baseline use of antithrombotic medication (aspirin, other antiplatelets, or anticoagulants) was allowed. The majority of exposures to antithrombotic medications were to aspirin.
The incidence of ARIA-H was 30% (106/349) in patients taking KISUNLA with a concomitant antithrombotic medication within 30 days compared to 29% (148/504) who did not receive an antithrombotic within 30 days of an ARIA-H event. 4% (2/504) in those who did not receive an antithrombotic.
The number of events and the limited exposure to non-aspirin antithrombotic medications limit definitive conclusions about the risk of ARIA or intracerebral hemorrhage in patients taking antithrombotic medications. One fatal intracerebral hemorrhage occurred in a patient taking KISUNLA in the setting of focal neurologic symptoms of ARIA and the use of a thrombolytic agent in Study 1, and one fatal intracerebral hemorrhage occurred in the setting of ARIA and the use of a thrombolytic agent in Study 2.
, tissue plasminogen activator) to a patient already being treated with KISUNLA. 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.
Caution should be exercised when considering the use of KISUNLA in patients with factors that indicate an increased risk for intracerebral hemorrhage and in particular for patients who need to be on anticoagulant therapy or patients with findings on MRI that are suggestive of cerebral amyloid angiopathy.
Radiographic Severity The radiographic severity of ARIA associated with KISUNLA was classified by the criteria shown in Table 5 .
Table 5:
ARIA MRI Classification Criteria a Includes new or worsening superficial siderosis. ARIA Type Radiographic Severity Mild Moderate Severe ARIA-E FLAIR hyperintensity confined to sulcus and/or cortex/subcortex white matter in one location <5 cm.
FLAIR hyperintensity 5 to 10 cm in single greatest dimension, or more than 1 site of involvement, each measuring <10 cm. FLAIR hyperintensity >10 cm with associated gyral swelling and sulcal effacement. One or more separate/independent sites of involvement may be noted.
ARIA-H microhemorrhage Less than or equal to 4 new incident microhemorrhages 5 to 9 new incident microhemorrhages 10 or more new incident microhemorrhages ARIA-H superficial siderosis 1 new a focal area of superficial siderosis 2 new focal areas of superficial siderosis Greater than 2 new focal areas of superficial siderosis In Study 1, the majority of ARIA-E radiographic events occurred early in treatment (within the first 24 weeks), although ARIA can occur at any time and patients can have more than one episode.
Resolution on MRI after the first ARIA-E event occurred in 63% of patients treated with KISUNLA by 12 weeks, 80% by 20 weeks, and 83% overall after detection. 4%, respectively. Among patients treated with KISUNLA, the rate of severe radiographic ARIA-H was highest in ApoE ε4 homozygotes (n=143) compared to heterozygotes (n=452) or noncarriers (n=255) at rates of 22%, 8%, and 4%, respectively.
Table 6 shows the maximum radiographic severity for ARIA-E, ARIA-H microhemorrhage, and ARIA-H superficial siderosis in Study 1 and Study 2. 3 )] . 3 )] . Use clinical judgment in considering whether to continue dosing in patients with recurrent ARIA-E.
3 )] . Enhanced clinical vigilance for ARIA is recommended during the first 24 weeks of treatment with KISUNLA. If a patient experiences symptoms suggestive of ARIA, clinical evaluation should be performed, including MRI if indicated.
If ARIA is observed on MRI, careful clinical evaluation should be performed prior to continuing treatment. There is limited experience in patients who continued dosing through asymptomatic but radiographically mild to moderate ARIA-E.
There are limited data for dosing patients who have experienced recurrent episodes of ARIA-E. , registries) to help further the understanding of Alzheimer's disease and the impact of Alzheimer's disease treatments. Providers and patients can contact 1-800-LillyRx (1-800-545-5979) for a list of currently enrolling programs.
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.
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. 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.