Abstract 15751: Pharmacodynamic Effect of ARO-ANG3, an Investigational RNA Interference Targeting Hepatic Angiopoietin-like Protein 3, in Patients With Hypercholesterolemia
Bibliographic record
Abstract
Background: Angiopoietin-like protein 3 (ANGPTL3) regulates triglyceride (TG) and lipoprotein (LP) metabolism by inhibiting liver and endothelial LP lipases and reduces plasma LDL-C. In Phase 1 Study AROANG1001 (NCT03747224), single and multiple doses of RNA interference therapeutic ARO-ANG3 (100, 200, or 300 mg; n=36) in healthy volunteers substantially reduced ANGPTL3, LDL-C, and other LPs (AHA 2019) compared with placebo (n=16). Purpose: We report preliminary results following repeat doses (days 1 and 29) of ARO-ANG3 in patients with heterozygous familial hypercholesterolemia (FH) with elevated LDL-C despite statin therapy and average LDL-C of 130 mg/dL. An additional group (non-FH patients) had LDL-C > 70 mg/dL despite statin therapy. Methods: Seventeen FH patients received open-label, subcutaneous, ARO-ANG3 100 mg (n=6), 200 mg (n=6), or 300 mg (n=5). Nine non-FH, high risk patients with elevated LDL-C not at goal received either 200 mg ARO-ANG3 (n=6) or placebo (n=3) using a randomized double-blind design. Pharmacodynamic markers included serum ANGPTL3, LDL-C, TG, and others. Results: Results are reported as of 04 May 2020. In FH patients, ARO-ANG3 significantly reduced mean ANGPTL3 levels between 62-92% at week 16 in a dose-dependent manner (Table). LDL-C (23-37%) and TG (25-43%) were consistently reduced at all doses (Table). The mean percent reductions in non-FH patients for ANGPTL3 (85%), LDL-C (28%), and TG (29%) were comparable to those in FH patients, despite their initially lower LDL-C at baseline. As of 15 May 2020, there were no drug-related serious or severe adverse events (AEs) or discontinuations and most AEs were mild. The most common AEs reported in subjects receiving ARO-ANG3 were respiratory tract infection (30% of subjects) and injection site AEs (13% of subjects). Conclusions: In FH and non-FH patients, repeat doses of ARO-ANG3 significantly reduced ANGPTL3, LDL-C, and TG, with favorable safety.
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How this classification was reachedexpand
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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| 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 | 0.000 |
| 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".