OR24-02 Case Series Of Canadian Patients With Homozygous Familial Hypercholesterolemia Treated With ANGPTL3 Inhibitor Evinacumab
Bibliographic record
Abstract
Abstract Disclosure: I. Shamsudeen: None. B.W. McCrindle: Consulting Fee; Self; Jansen Pharmaceuticals, Amryt, Ultragenyx, Chiesi, Esperion. R.A. Hegele: Advisory Board Member; Self; Amgen Inc, HLS Pharmaceuticals, Novartis Pharmaceuticals. Consulting Fee; Self; Akcea Therapeutics, Ultragenyx, Medison, Acasti, Amgen Inc, Novartis Pharmaceuticals, Amryt, Amgen Inc, Pfizer, Inc., Arrowhead, Sanofi, HLS Pharmaceuticals, Regeneron Pharmaceuticals. Background: Homozygous familial hypercholesterolemia (HoFH) is an ultrarare, life-threatening condition characterized by markedly elevated levels of low-density lipoprotein cholesterol (LDL-C) due to biallelic LDL receptor variants. Patients have an increased risk of premature atherosclerotic cardiovascular disease (ASCVD). Traditional lipid-lowering agents are minimally effective and the gold standard treatment is serial apheresis. Recently, an angiopoietin-like protein 3 (ANGPTL3) inhibitor, evinacumab, was introduced as a promising new treatment for HoFH. It was FDA-approved in 2021, but is currently available in Canada only through clinical trials or special access programs. Case Presentations: The first five Canadian HoFH patients to receive evinacumab via special access are presented. Their mean age is 24.6 years (SD = 13.9). As of December 2022, they have received evinacumab 15 mg/kg intravenously every four weeks for a mean of 12.2 months (SD = 11.3). Their mean incremental LDL-C reduction is 49.4% (SD = 8.9) on evinacumab along with reduced apheresis frequency for those on serial apheresis. Safety labs for all patients are normal. Brief case summaries are as follows: (a) Patient A is a 36-year-old man with severe ASCVD who has been on evinacumab for 30 months, in addition to a statin, ezetimibe, evolocumab and LDL-apheresis. His time-averaged LDL-C has decreased by 46.2%, from 4.76 to 2.56 mmol/L (184 to 99 mg/dL), on evinacumab. (b) Patient B is a 17-year-old male with elevated LDL-C levels despite being on a statin, ezetimibe and LDL-apheresis. After 14 months on evinacumab, his time-averaged LDL-C reduced by 40.3%, from 8.75 to 5.22 mmol/L (338 to 202 mg/dL). (c) Patient C is a 30-year-old woman with ASCVD and xanthomas on a statin and ezetimibe, but not apheresis. She has been on evinacumab for 12 months with a 57.7% reduction in LDL-C, from 11.43 to 4.83 mmol/L (442 to 187 mg/dL). (d) Patient D is a 36-year-old man with ASCVD on a statin, ezetimibe, evolocumab and lomitapide in addition to plasmapheresis. He started evinacumab 2 months ago and has already had a 42.6% decrease in time-averaged LDL-C, from 4.34 to 2.49 mmol/L (168 to 96 mg/dL). (e) Patient E is a 4-year-old boy with HoFH and xanthomas on a statin, ezetimibe and plasmapheresis. After 3 months of treatment with evinacumab, his time-averaged LDL-C decreased by 59.9%, from 9.45 to 3.79 mmol/L (365 to 147 mg/dL). Concurrently, he has developed unexplained intermittent abdominal pain, with temporary suspension of evinacumab pending further assessment. Discussion: Five HoFH patients with distinctive histories, baseline treatments and ASCVD have all shown marked improvement in LDL-C levels with a mean reduction of 49.4% on evinacumab on top of existing therapy. Overall, observations from our case series suggest that evinacumab is an effective new treatment for HoFH, a life-threatening condition with few therapeutic options. Presentation: Saturday, June 17, 2023
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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 | 0.001 |
| 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".