PALISADE: PLOZASIRAN DECREASES THE RISK OF ACUTE PANCREATITIS AND MAY IMPROVE QUALITY OF LIFE IN FAMILIAL CHYLOMICRONEMIA SYNDROME
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Bibliographic record
Abstract
Therapeutic Area ASCVD /CVD Risk Reduction Background FCS causes life-threatening Acute Pancreatitis (AP) and may be due to genetic defects in the enzyme lipoprotein lipase (LPL) which impair the circulatory clearance of chylomicrons (CMs) and triglycerides (TGs). Other clinical manifestations collectively impair QoL. Plozasiran is a siRNA that reduces hepatic apolipoprotein (apo) C-III, thereby effectively lowering extremely high TGs. We describe effects of plozasiran on AP outcomes and QoL in patients with FCS. Methods PALISADE was a Phase 3 double blind, placebo-controlled trial of 75 adults with FCS (59% were genetically confirmed) on best standard-of-care. Patients were randomized to quarterly dosed plozasiran (25 or 50 mg SC) or placebo for 12 months. TG lowering was the primary endpoint and adjudicated rates of AP were a key (alpha-controlled) secondary endpoint. Qualitative patient reported outcomes on composite measures of QoL, EORTC-QLQ-C30, PAN-26 and EQ-5D-5L were exploratory. Results Plozasiran lowered median TG levels from >2000 to 544 mg/dL at 12 months (p<0.001), independent of a confirmed FCS genotype. All key secondary endpoints (previously reported) showed significant benefits of plozasiran. Nine AP episodes in 7 patients were positively adjudicated: patients receiving plozasiran achieved an 83% reduction in the risk of developing AP versus placebo, (p<0.03). Placebo patients with AP transitioned to open label treatment, limiting the ability to assess cumulative events. Plozasiran was well-tolerated. Severe and serious events were less common with Plozasiran than placebo. AP severity differed: 6 severe and 1 moderate event occurred on placebo vs 1 moderate and 1 mild event on Plozasiran. Placebo patients spent 47 days in the hospital vs 10 days with Plozasiran. More patients in placebo experienced abdominal pain leading to AP. Absolute changes in various domain scores of the selected patient reported outcomes correlated with improvements. Most symptom domains improved in the QoL assessments, some with clinically meaningful scores > -10 points, i.e. significant improvements in appetite loss, -15.9, insomnia, -16.8 (p<0.05, both). Functional domain scores improved, some with clinically meaningful scores > +10 points, i.e. improvements in role function, +14.8 and emotional function, +11.8 (p<0.05, both), and health care satisfaction, +14.7. Clinically meaningful improvements were shown for appetite loss, insomnia, cognitive functioning, emotional functioning, and role functioning in the plozasiran treated subjects compared to placebo (nominal p-values of <0.05). Conclusions Plozasiran significantly reduced TG and AP while improving QoL in the PALISADE trial.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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