Kisunla Drug Information
Generic name: DONANEMAB-AZBT
Uses of Kisunla
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.
Dosage & Administration of Kisunla
Patient Selection Confirm the presence of amyloid beta pathology prior to initiating treatment.
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 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. If an infusion is missed, resume administration every 4 weeks at the same dose as soon as possible.
Monitoring and Dosing Interruption for Amyloid Related Imaging Abnormalities KISUNLA can cause amyloid related imaging abnormalities -edema (ARIA-E) and -hemosiderin deposition (ARIA-H). Monitoring for ARIA Obtain a recent baseline brain magnetic resonance imaging (MRI) prior to initiating treatment with KISUNLA. 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. Severe: incapacitating, with inability to work or to perform normal daily activity. 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. c See Table 5 for MRI radiographic severity. 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. c See Table 5 for MRI radiographic severity. 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.
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. Use only 0.9% sodium chloride injection for dilution.
Table 4: Preparation of KISUNLA 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. 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 ) for up to 12 hours.
Do not freeze the diluted KISUNLA solution. Storage times include the duration of infusion.
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. 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.
| *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 |
| 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 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. | |||
| c See Table 5 for MRI radiographic severity [Warning and Precautions ( 5.1 )]. | |||
| 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 | ||
| 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. | |||
| c See Table 5 for MRI radiographic severity [Warning and Precautions ( 5.1 )]. | |||
| 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 | |
| a final concentration of 4 mg/mL to 10 mg/mL | ||||
| b 2 vials of KISUNLA | ||||
| c 3 vials of KISUNLA | ||||
| d 4 vials of KISUNLA | ||||
| KISUNLA Dose (mg) | KISUNLA Volume (mL) | Volume of 0.9% Sodium Chloride Injection Diluent (mL) | Final Volume of Diluted Solution to be Infused (mL) | Final Concentration of Diluted Solution (mg/mL) a |
| 350 mg | 20 mL | 15 mL to 67.5 mL | 35 mL to 87.5 mL | 350 mg/87.5 mL (4 mg/mL) to 350 mg/35 mL (10 mg/mL) |
| 700 mg | 40 mL b | 30 mL to 135 mL | 70 mL to 175 mL | 700 mg/175 mL (4 mg/mL) to 700 mg/70 mL (10 mg/mL) |
| 1,050 mg | 60 mL c | 45 mL to 202.5 mL | 105 mL to 262.5 mL | 1,050 mg/262.5 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) |
Side Effects of Kisunla
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. The safety of KISUNLA has been evaluated in 3727 patients with Alzheimer's disease who received at least one dose of KISUNLA intravenously. 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). Serious adverse reactions of intestinal perforation occurred in two patients (0.2%) treated with KISUNLA compared to one patient (0.1%) on 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 |
Warnings & Cautions for Kisunla
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.
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. 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. In Study 1, symptomatic ARIA-E occurred in 6% of patients through 18 months of treatment with KISUNLA.
Clinical symptoms associated with ARIA-E resolved in approximately 85% of those patients. There was no increase in isolated ARIA-H (i.e., ARIA-H in patients who did not also experience ARIA-E) for KISUNLA compared to placebo. 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. 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.
The small number of events and limited exposure in the ApoE ε4 subgroups limit definitive conclusions about the risk of ARIA-E. The recommendations for management of ARIA do not differ based on ApoE ε4 carrier status. 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 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. Additional caution should be exercised when considering the administration of antithrombotics or a thrombolytic agent (e.g., 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 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.
Table 6 shows the maximum radiographic severity for ARIA-E, ARIA-H microhemorrhage, and ARIA-H superficial siderosis in Study 1 and Study 2. Table 6: Maximum Radiographic Severity in Patients Treated with KISUNLA in Study 1 Study Monitoring and Dose Management Guidelines Recommendations for dosing in patients with ARIA-E depend on clinical symptoms and radiographic severity. Recommendations for dosing in patients with ARIA-H depend on the type of ARIA-H and radiographic severity.
Use clinical judgment in considering whether to continue dosing in patients with recurrent ARIA-E. Baseline brain MRI and periodic monitoring with MRI are recommended. 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. Providers should encourage patients to participate in real world data collection (e.g., 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.
Hypersensitivity Reactions
Hypersensitivity reactions, including anaphylaxis and angioedema, have occurred in patients who were treated with KISUNLA. 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.
Infusion-Related Reactions 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.
Infusion-related reactions were mostly mild (47%) or moderate (50%) in severity. 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.
| 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 |
| *Administered as Dosing Regimen 2 over 12 months of treatment | ||||||
| Study 1 Dosing Regimen 1 N=853 % | Study 2 Dosing Regimen 2 N=212 % | |||||
| Mild | Moderate | Severe | Mild | Moderate | Severe | |
| ARIA-E | 7 | 15 | 2 | 6 | 9 | 0 |
| ARIA-H microhemorrhage | 17 | 4 | 5 | 17 | 3 | 2 |
| ARIA-H superficial siderosis | 6 | 4 | 5 | 4 | 3 | 1 |
Pregnancy Safety for Kisunla
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 respectively.
The background risk of major birth defects and miscarriage for the indicated population is unknown.
Pediatric Use of Kisunla
Pediatric Use Safety and effectiveness in pediatric patients have not been established.
Contraindications for Kisunla
KISUNLA is contraindicated in patients with known serious hypersensitivity to donanemab-azbt or to any of the excipients. Reactions have included anaphylaxis.
Clinical Studies of Kisunla
Study 1 The efficacy of KISUNLA was evaluated in a double-blind, placebo-controlled, parallel-group study (Study 1, NCT04437511) in patients with Alzheimer's disease (patients with confirmed presence of amyloid pathology and mild cognitive impairment or mild dementia stage of disease, consistent with Stage 3 and Stage 4 Alzheimer's disease). Patients were enrolled with a Mini-Mental State Examination (MMSE) score of ≥20 and ≤28 and had a progressive change in memory function for at least 6 months. Patients were included in the study based on visual assessment of tau PET imaging with flortaucipir and standardized uptake value ratio (SUVR).
Patients were enrolled with or without concomitant approved therapies (cholinesterase inhibitors and the N-methyl-D-aspartate antagonist memantine) for Alzheimer's disease. Patients could enroll in an optional, long-term extension. The treatment was switched to placebo based on amyloid PET levels measured at Week 24, Week 52, and Week 76.
Additionally, dose adjustments were allowed for treatment-emergent ARIA or symptoms that then showed ARIA-E or ARIA-H on MRI. At baseline, mean age was 73 years, with a range of 59 to 86 years. The primary efficacy endpoint was change in the integrated Alzheimer's Disease Rating Scale (iADRS) score from baseline to 76 weeks.
The iADRS is a combination of two scores: the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog 13 ) and the Alzheimer's Disease Cooperative Study – instrumental Activities of Daily Living (ADCS-iADL) scale. The total score ranges from 0 to 144, with lower scores reflecting worse cognitive and functional performance. Other efficacy endpoints included Clinical Dementia Rating Scale – Sum of Boxes (CDR-SB), ADAS-Cog 13, and ADCS-iADL.
There were two primary analysis populations based on tau PET imaging with flortaucipir: 1 low/medium tau level population (defined by visual assessment and SUVR of ≥1.10 and ≤1.46), and 2 combined population of low/medium plus high tau (defined by visual assessment and SUVR >1.46) population. Patients treated with KISUNLA demonstrated a statistically significant reduction in clinical decline on iADRS compared to placebo at Week 76 in the combined population (2.92, p<0.0001) and the low/medium tau population (3.25, p<0.0001). Patients treated with KISUNLA demonstrated a statistically significant reduction in clinical decline on CDR-SB compared to placebo at Week 76 in the combined population (-0.70, p<0.0001) ( see Figure 2 and Table 8 ).
There were also statistically significant differences (p<0.001) between treatment groups as measured by ADAS-Cog 13 and ADCS-iADL at Week 76 ( see Table 9 ). Dosing was continued or stopped in response to observed effects on amyloid imaging. Amyloid PET values may increase after treatment with donanemab is stopped.
There is no data beyond the 76-week duration of Study 1 to guide whether additional dosing with KISUNLA may be needed for longer-term clinical benefit. Figure 2: CDR-SB Change From Baseline in Combined Population Through 76 Weeks in Study 1 a a *p<0.0001 versus placebo. Table 9: Efficacy Analysis Results in Combined Population at Week 76 a in Study 1 Figure 2 Study 2 Study 2 (NCT05738486) was a randomized, double-blind study investigating the effect of different KISUNLA dosing regimens on ARIA-E and change from baseline in amyloid in adults with Alzheimer's disease (patients with confirmed amyloid pathology and mild cognitive impairment or mild dementia stage of disease).
Inclusion and exclusion criteria were the same as Study 1 except that tau PET was not an inclusion criterion. Patients were randomized to receive Dosing Regimen 1 (N=207), or one of three alternative regimens, including Dosing Regimen 2 (N=212) in a 1:1:1:1 ratio. The treatment period was up to 72 weeks, and treatment stopping criteria based on amyloid PET were the same as Study 1.
Of the 212 patients receiving Dosing Regimen 2, the mean age was 74 years. The primary endpoint of the study was the proportion of patients with any occurrence of ARIA-E. ARIA-E occurred at a higher incidence in ApoE ε4 homozygotes, compared to heterozygotes, with the lowest incidence in noncarriers.
The small number of events and limited exposure in the ApoE ε4 subgroups limit definitive conclusions about the risk of ARIA-E. Table 10: Cumulative Incidence of ARIA-E and ARIA-H in 52 Weeks, Overall and by ApoE e4 Genotype, in Study 2
| a Abbreviations: ADAS-Cog 13 = Alzheimer's Disease Assessment Scale – 13-item Cognitive Subscale; ADCS-iADL = Alzheimer's Disease Cooperative Study – instrumental Activities of Daily Living subscale; CDR-SB = Clinical Dementia Rating Scale – Sum of Boxes; NCS2 = natural cubic spline with 2 degrees of freedom; MMRM = mixed model for repeated measures. | ||
| b Assessed using MMRM analysis. | ||
| c Assessed using NCS2 analysis. | ||
| d Percent slowing of decline relative to placebo: difference of adjusted mean change from baseline between treatment groups divided by adjusted mean change from baseline of placebo group at Week 76. | ||
| Clinical Endpoints | KISUNLA (N = 860) | Placebo (N = 876) |
| CDR-SB b | ||
| Mean baseline | 3.92 | 3.89 |
| Adjusted mean change from baseline | 1.72 | 2.42 |
| Difference from placebo (%) d | -0.70 (29%) p<0.0001 | -- |
| ADAS-Cog 13 c | ||
| Mean baseline | 28.53 | 29.16 |
| Adjusted mean change from baseline | 5.46 | 6.79 |
| Difference from placebo (%) d | -1.33 (20%) p=0.0006 | -- |
| ADCS-iADL c | ||
| Mean baseline | 47.96 | 47.98 |
| Adjusted mean change from baseline | -4.42 | -6.13 |
| Difference from placebo (%) d | 1.70 (28%) p=0.0001 | -- |
| 1 Kaplan-Meier estimates of cumulative incidence | ||
| Abbreviations: CI = confidence interval, RD = risk difference | ||
| Dosing Regimen 1 | Dosing Regimen 2 | |
| N=207 | N=212 | |
| ARIA-E Overall | ||
| n (incidence, %) | 50 (24.9) | 33 (16.2) |
| RD (95% CI) | - | 8.7 (0.8, 16.5) |
| ARIA-H Overall | ||
| n (incidence, %) | 56 (28.1) | 51 (25.2) |
| RD (95% CI) | - | 2.9 (-5.8, 11.6) |
| Homozygotes, N | 21 | 21 |
| ARIA-E | ||
| n (incidence 1, %) | 12 (57.1) | 5 (24.4) |
| RD (95% CI) | - | 32.7 (4.4, 60.9) |
| ARIA-H | ||
| n (incidence 1, %) | 10 (47.6) | 6 (28.6) |
| RD (95% CI) | - | 19.0 (-9.8, 47.8) |
| Heterozygotes, N | 112 | 115 |
| ARIA-E | ||
| n (incidence 1, %) | 27 (25.0) | 18 (16.4) |
| RD (95% CI) | - | 8.6 (-2.2, 19.3) |
| ARIA-H | ||
| n (incidence 1, %) | 34 (31.8) | 33 (30.8) |
| RD (95% CI) | - | 1.0 (-11.5, 13.5) |
| ApoE noncarriers, N | 72 | 75 |
| ARIA-E | ||
| n (incidence 1, %) | 11 (15.6) | 10 (13.8) |
| RD (95% CI) | - | 1.8 (-9.8, 13.5) |
| ARIA-H | ||
| n (incidence 1, %) | 12 (17.2) | 12 (16.4) |
| RD (95% CI) | - | 0.8 (-11.5, 13.1) |
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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