LONG-TERM EFFICACY OF EVINACUMAB IN PATIENTS WITH HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA: RESULTS FROM SUBGROUP ANALYSES
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
Pharmacologic Therapy Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder characterized by severely elevated low-density lipoprotein cholesterol (LDL-C) and increased risk of early-onset atherosclerotic cardiovascular disease. Despite treatment with multiple lipid-lowering therapies (LLTs), most patients with HoFH do not attain guideline-recommended LDL-C treatment goals. In a phase 3 trial (NCT03409744), evinacumab, an angiopoietin-like 3 inhibitor, substantially reduced mean LDL-C by 43.6% from baseline to Week 24. Here, we report on the long-term LDL-C lowering efficacy of evinacumab analyzed by patient subgroups from the open-label treatment period (OLTP) of this phase 3 trial. This single-arm, open-label, phase 3 study (NCT03409744) comprised patients with HoFH aged ≥12 years who were evinacumab-naïve or had previously received evinacumab in other trials. The study included a run-in period (≤10 weeks), a screening period (2 weeks), an OLTP (≤192 weeks), and a follow-up period (24 weeks). In the OLTP, all patients received intravenous evinacumab 15 mg/kg every 4 weeks alongside optimized LLT. Overall, 116 patients were enrolled with a mean (standard deviation [SD]) age of 38.8 (15.9) years. The proportion of male and female patients was similar (50.9% vs 49.1%, respectively). Most patients were White (69.0%) or Asian (10.3%). At baseline, mean (SD) LDL-C was 261.0 (160.1) mg/dL. Evinacumab reduced mean (SD) LDL-C from baseline to Week 96 by 57.6% (16.7%), 36.4% (54.6%), and 38.0% (52.9%) in patients <18 years of age, patients ≥18 years of age, and overall, respectively. Among female and male patients, mean (SD) LDL-C reduction from baseline to Week 96 was 48.8% (32.3%) and 30.5% (62.6%), respectively. Mean (SD) LDL-C reduction from baseline to Week 96 was 43.1% (36.9%) in patients with null-null variants in either the low-density lipoprotein receptor (LDLR) gene or the low-density lipoprotein receptor adapter protein 1 (LDLRAP1) gene; mean (SD) LDL-C reduction was 35.1% (62.4%) in patients with non-null variants in LDLR or LDLRAP1. From baseline to Week 96, reductions in LDL-C with evinacumab were observed irrespective of background LLT (Figure). In patients with HoFH, evinacumab showed substantial and sustained LDL-C reduction irrespective of age, sex, LDLR genotype, and background LLT.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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