Clarity AD: A pivotal study measuring early and long-term efficacy and safety of LEQEMBI®1-5
Core placebo-controlled period (0-18 months)1,2:
Long-Term Extension (LTE) (18-48 months)3-5:
Primary objective: Evaluate the effect of LEQEMBI as measured by Clinical Dementia Rating-Sum of Boxes (CDR-SB)
- Global, placebo-controlled, double-blind, parallel-group, randomized clinical trial
- 1795 patients with mild cognitive impairment (MCI) due to Alzheimer's disease (AD) or mild AD dementia with confirmed amyloid beta (Aß) pathology
Randomization 1:1
LEQEMBI
10 mg/kg once every 2 weeks (infusion) n=898
Placebo
once every 2 weeks (infusion) n=897
94%
of patients in the LEQEMBI arm who completed the Core period opted to continue in the LTE after 18 months6-8
Long-Term Extension (LTE)(18-48 months)3-5:
Primary objective: Evaluate long-term safety and whether the effect of LEQEMBI is maintained over time (CDR-SB)
- Global, open-label, single-arm study
- Patients in the Core period were given the option to participate in the extension phase; some remained on infusion while others were on different subcutaneous maintenance doses
94%
of patients in the LEQEMBI arm who completed the Core period opted to continue in the LTE after 18 months6-8
Alzheimer’s Disease Neuroimaging Initiative (ADNI): A matched untreated cohort used to simulate control3,4
- A global (US & Canada) research study that follows the natural progression of AD, including imaging, biomarkers, genetics, and neurocognitive tests and that actively evaluates the investigation and development of treatments for AD
- ADNI is an untreated observational cohort (n=436 at baseline, followed for 48 months) that was a prespecified matched ADNI cohort used to design the Clarity AD study, based on demographics and clinical characteristics
- ADNI participants were not part of the Clarity AD study; instead, they were exclusively used as a historical control line in this observational analysis
Patient characteristics
LEQEMBI was studied in MCI and mild AD dementia patients9
Key patient characteristics in the Clarity AD study2
Taking concomitant medications
- 52.9% of patients (in the US and globally) were taking acetylcholinesterase inhibitors (AChEIs) and/or memantine
- 5.7% of US patients received anticoagulant therapy*
Diverse population
- 27% enrollment of Hispanic (22.5%) and Black (4.5%) patients in the United States
Comorbid conditions
- 63.7% of US patients had ≥2 comorbidities: hypertension, hyperlipidemia, ischemic heart disease, diabetes, or obesity
The majority of patients had MCI due to AD1,9
- 61.5% MCI due to AD
- 38.5% mild AD dementia
*Caution should be exercised when considering the use of LEQEMBI 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.1
AD, Alzheimer's disease; MCI, mild cognitive impairment; MRI, magnetic resonance imaging.
Additional demographics
Baseline characteristics in Clarity AD: A broad population, representative of patients with MCI due to AD and mild AD dementia9
| Baseline characteristics | LEQEMBI | Placebo |
|---|---|---|
| 10 mg/kg once every 2 weeks (n=859) | (n=875) | |
| Age, mean (SD), years | 71.4 (7.9) | 71.0 (7.8) |
| Female, n (%) | 443 (51.6) | 464 (53.0) |
| White, n (%) | 655 (76.3) | 677 (77.4) |
| Years since diagnosis, mean (SD) | 1.41 (1.51) | 1.34 (1.54) |
| Years since onset of symptoms, mean (SD) |
4.13 (2.35) | 4.15 (2.53) |
| CDR global score=0.5, n (%) |
694 (80.8) | 706 (80.7) |
| MCI due to AD, n (%) |
528 (61.5) | 544 (62.2) |
| Mild dementia due to AD, n (%) | 331 (38.5) | 331 (37.8) |
| ApoE ε4 status, n (%) |
||
| Noncarrier | 267 (31.1) | 275 (31.4) |
| Carrier | 592 (68.9) | 600 (68.6) |
| Heterozygotes | 456 (53.1) | 468 (53.5) |
| Homozygotes | 136 (15.8) | 132 (15.1) |
| On AChEIs and/ or memantine, n (%) |
447 (52.0) | 468 (53.5) |
| CDR-SB, mean (SD) | 3.17 (1.34) | 3.22 (1.34) |
| PET Centiloid, mean (SD) | 77.92 (44.84) | 75.03 (41.82) |
| ADAS-Cog14, mean (SD) | 24.45 (7.08) | 24.37 (7.56) |
| ADCOMS, mean (SD) | 0.398 (0.147) | 0.400 (0.147) |
| ADCS MCI-ADL, mean (SD) | 41.2 (6.6) | 40.9 (6.9) |
| MMSE, mean (SD) | 25.5 (2.2) | 25.6 (2.2) |
In the United States, LEQEMBI was studied in a broad range of patients2
- 27% enrollment of Hispanic (22.5%) and Black (4.5%) people2
- 63.7% of patients had at least 2 comorbid conditions*2
- 5.7% received anticoagulation2
Because intracerebral hemorrhages >1 cm in diameter have been observed in patients taking LEQEMBI, additional caution should be exercised when considering the administration of anticoagulants or a thrombolytic agent (eg, tissue plasminogen activator) to a patient already being treated with LEQEMBI1
*Comorbid conditions include hypertension, hyperlipidemia, ischemic heart disease, diabetes, and obesity.2
ADAS-Cog14, Alzheimer’s Disease Assessment Scale–Cognitive Subscale 14-item version; ADCOMS, Alzheimer’s Disease Composite Score; ADCS MCI-ADL, Alzheimer’s Disease Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment; ApoE, apolipoprotein E; CDR, Clinical Dementia Rating; MMSE, Mini-Mental State Examination; PET, positron emission tomography; SD, standard deviation.
Comorbidities & comedications represented in the patient population
Baseline characteristics in Clarity AD: A broad population, representative of patients with MCI due to AD and mild AD dementia2
| Baseline characteristics | Combined Total | United States |
|---|---|---|
| Characteristic | (N=1795) | (n=948) |
| Comorbidities | ||
| Hypertension, n (%) | 993 (55.3) | 612 (64.6) |
| Hyperlipidemia, n (%) | 1085 (60.4) | 674 (71.1) |
| Ischemic heart disease, n (%) | 291 (16.2) | 189 (19.9) |
| Diabetes, n (%) | 271 (15.1) | 180 (19.0) |
| Obesity, n (%) | 298 (16.6) | 229 (24.2) |
| At least 2 comorbidities above, n (%) | 917 (51.1) | 604 (63.7) |
| At least 3 comorbidities above, n (%) | 441 (24.6) | 319 (33.6) |
| At least 4 comorbidities above, n (%) | 139 (7.7) | 111 (11.7) |
| At least 5 comorbidities above, n (%) | 25 (1.4) | 22 (2.3) |
| Comedications | ||
| Anticoagulants | 80 (4.5) | 54 (5.7) |