EFFICACY AND SAFETY OF INCLISIRAN BY BASELINE BODY MASS INDEX: A POST HOC POOLED ANALYSIS OF THE ORION-9, ORION-10 AND ORION-11 PHASE III RANDOMIZED CONTROLLED TRIALS
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
ASCVD/CVD Risk Factors Excessive bodyweight, often associated with dyslipidemia, may affect the pharmacology of drugs. Inclisiran, a small interfering RNA targeting PCSK9 hepatic mRNA, is an effective LDL-C lowering agent with twice-yearly subcutaneous dosing (after the initial and 3-month doses). The aim of this analysis was to assess the efficacy and safety of inclisiran in patients with heterozygous familial hypercholesterolemia, atherosclerotic cardiovascular disease (ASCVD) or ASCVD risk equivalent across body mass index (BMI) strata. In this post hoc analysis from ORION-9 (NCT03397121), ORION-10 (NCT03399370) and ORION-11 (NCT03400800), eligible patients were randomized 1:1 to receive 300 mg inclisiran sodium (equivalent to 284 mg inclisiran) or placebo at baseline, Day 90 and 6-monthly thereafter. Analysis was stratified by baseline BMI: <25, 25–<30, 30–<35 or ≥35 kg/m2. Percentage change in atherogenic lipids from baseline at Day 510 was evaluated. Safety was assessed over 540 days. Baseline demographic and clinical characteristics including atherogenic lipid levels were mostly balanced between treatment arms and across BMI strata (Table). Percentage change in atherogenic lipids from baseline at Day 510 was significantly greater with inclisiran vs placebo within each BMI stratum (Table). Treatment-emergent adverse events (TEAE) and treatment-emergent serious adverse events were generally similar between treatment arms and were reported more frequently with increasing BMI strata (data not shown). Clinically relevant TEAEs at the injection site were reported more frequently with inclisiran vs placebo similarly across strata, but all were mild or moderate. Twice-yearly dosing with inclisiran (after the initial and 3-month doses) provided effective and sustained lipid lowering in patients, irrespective of their baseline BMI, and was generally well tolerated.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.023 | 0.009 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.011 | 0.003 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it