Abstract 12450: Long-Term Efficacy and Safety of Lomitapide for the Treatment of Homozygous Familial Hypercholesterolemia: Results of the Phase 3 Extension Trial
Bibliographic record
Abstract
Background: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic condition characterized by highly elevated low-density lipoprotein cholesterol (LDL-C) levels and high cardiovascular disease risk. Lomitapide, an oral microsomal triglyceride transfer protein inhibitor, was approved for the treatment of adult HoFH based on a small phase 3 study. We report efficacy and safety results from the phase 3 long-term extension study. Methods: Eligible HoFH patients completing the 78-wk phase 3 pivotal trial were enrolled into a single-arm extension study where lomitapide was administered daily at the maximum tolerated dose (5-60mg/d) until lomitapide was commercially available in the patient’s country. Concurrent lipid-lowering therapies, including apheresis, were permitted. Results: Nineteen of 23 patients who completed the pivotal study entered the extension trial (9/19 apheresis) with 16 patients completing all end of study assessments. Mean treatment duration was 4.8 yrs (range 2.1-5.7 yrs, median 5.1 yrs). Lomitapide efficacy was maintained throughout the study (Table). Reported adverse events were similar to those in the pivotal phase 3 study (chiefly gastrointestinal). Five patients (26%) experienced transient alanine aminotransferase (ALT) elevations ≥5x upper limit of normal (ULN) that were successfully managed by dose adjustment in all but one patient who was discontinued due to persistent excessive alcohol use. One 58 year-old patient with known CAD had sudden cardiac death. Median hepatic fat increased by 10% above baseline after 3 yrs and stabilized through the treatment period (Table). No other clinically relevant findings were identified to date. Conclusions: The long-term efficacy of lomitapide was maintained up to 5.7 yrs in patients completing the phase 3 trial with no new safety signals observed. The clinical significance of the increase in hepatic fat remains unknown.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".