Recently, FDA gave full approval to the anti-amyloid Alzheimer's drug LEQEMBI (lecanemab). I was interested in what the exclusion criteria were, for example, if patients with mixed Alzheimer and Parkinson's disease were excluded.
It was quite a chase to find the exclusion criteria. Here are some places you can't find it:
The FDA label for LEQEMBI here.
The NEJM pivotal trial (January 2023, Van Dyck et al.) here.
The Supplement to NEJM here.
It's not that the exclusion criteria are trivial. You DO see, for example, from the Screening & Randomization Flow Chart (van Dyck Fig. 1) that 5967 patients were screened for eligibility, and 3555 failed (60%). But why did they fail?
Keep looking.
You can find a listing of exclusion criteria at ClinicalTrials.org NCT03887455. With all these exclusions, it's always still a gray area to ask "if the patients are representative of a Medicare population."
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Exclusion Criteria
- Any neurological condition that may be contributing to cognitive impairment above and beyond that caused by the participant's Alzheimer's disease
- History of transient ischemic attacks (TIA), stroke, or seizures within 12 months of Screening
- Any psychiatric diagnosis or symptoms (example, hallucinations, major depression, or delusions) that could interfere with study procedures in the participant
- Geriatric Depression Scale (GDS) score >=8 at Screening
- Contraindications to MRI scanning, including cardiac pacemaker/defibrillator, ferromagnetic metal implants (example in skull and cardiac devices other than those approved as safe for use in MRI scanners)
- Evidence of other clinically significant lesions on brain MRI at Screening that could indicate a dementia diagnosis other than Alzheimer's disease
- Other significant pathological findings on brain MRI at screening, including but not limited to: more than 4 microhemorrhages (defined as 10 millimeter [mm] or less at the greatest diameter); a single macrohemorrhage >10 mm at greatest diameter; an area of superficial siderosis; evidence of vasogenic edema; evidence of cerebral contusion, encephalomalacia, aneurysms, vascular malformations, or infective lesions; evidence of multiple lacunar infarcts or stroke involving a major vascular territory, severe small vessel, or white matter disease; space occupying lesions; or brain tumors (however, lesions diagnosed as meningiomas or arachnoid cysts and <1 centimeter [cm] at their greatest diameter need not be exclusionary)
- Any immunological disease which is not adequately controlled, or which requires treatment with immunoglobulins, systemic monoclonal antibodies (or derivatives of monoclonal antibodies), systemic immunosuppressants, or plasmapheresis during the study
- Participants with a bleeding disorder that is not under adequate control (including a platelet count <50,000 or international normalized ratio [INR] >1.5 for participants who are not on anticoagulant treatment, example, warfarin). Participants who are on anticoagulant therapy should have their anticoagulant status optimized and be on a stable dose for 4 weeks before Screening. Participants who are on anticoagulant therapy are not permitted to participate in cerebrospinal fluid (CSF) assessments
- Any other medical conditions (example, cardiac, respiratory, gastrointestinal, renal disease) which are not stably and adequately controlled, or which in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments
- Participation in a clinical study involving any therapeutic monoclonal antibody, protein derived from a monoclonal antibody, immunoglobulin therapy, or vaccine within 6 months before screening unless it can be documented that the participant was randomized to placebo
- Participation in a clinical study involving any anti-amyloid therapies (including any monoclonal antibody therapies and any β-site amyloid precursor protein cleaving enzyme [BACE] inhibitor therapies) unless it can be documented that the participant only received placebo
- Participants who have any known prior exposure to lecanemab
- Participants who were dosed in a clinical study involving any new chemical entities for AD within 6 months prior to screening unless it can be documented that the participant was in a placebo treatment arm
Extension Phase: Exclusion Criteria
- Participants who discontinued early from the Core Study
Participants who develop the following conditions from the time of Screening for the Core Study to the start of the Extension Phase
- Any neurological condition that may be contributing to cognitive impairment above and beyond that caused by the participant's AD
- Any psychiatric diagnosis or symptoms, (example, hallucinations, major depression, or delusions) that could interfere with study procedures in the participant
- Contraindications to MRI scanning, including cardiac pacemaker/defibrillator, ferromagnetic metal implants (example, in skull and cardiac devices other than those approved as safe for use in MRI scanners)
- Other significant pathological findings on brain MRI during the Core Study including but not limited to: cerebral contusion, encephalomalacia, aneurysms, vascular malformations, or infective lesions; evidence of multiple lacunar infarcts or stroke involving a major vascular territory, severe small vessel, or white matter disease; space occupying lesions; or brain tumors will be exclusionary if based on the opinion of the investigator, with consultation of medical monitor, these findings may interfere with the study procedures or safety
- Hypersensitivity to BAN2401 or any of the excipients, or to any monoclonal antibody treatment
- Any immunological disease which is not adequately controlled, or which requires chronic treatment with immunoglobulins, systemic monoclonal antibodies (or derivatives of monoclonal antibodies), systemic immunosuppressants, or plasmapheresis during the study
- Any other clinically significant abnormalities in physical examination, vital signs, laboratory tests, or ECG, which in the opinion of the investigator require further investigation or treatment or which may interfere with study procedures or safety.
- Malignant neoplasms (except for basal or squamous cell carcinoma in situ of the skin, or localized prostate cancer in male participants) that are not stably and adequately controlled or which, based on the opinion of the investigator, may interfere with the participant's safety or participation in the study
- Any other medical conditions (example, cardiac, respiratory, gastrointestinal, renal disease) which are not stably and adequately controlled, or which in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments
- Severe visual or hearing impairment that would prevent the participant from performing psychometric tests accurately
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For a brief blog on male/female differences, here.
There's probably more about exclusion criteria buried in the review dossiers and decks of the June 2023 FDA Ad Comm, here.
