Efficacy of evinacumab in patients with severe hypertriglyceridemia and a history of severe hypertriglyceridemia-related acute pancreatitis: A phase 2b trial

BACKGROUND Severe hypertriglyceridemia (sHTG) is an established risk factor for acute pancreatitis (AP). OBJECTIVE To evaluate the efficacy of a 20 mg/kg dose of intravenous evinacumab vs placebo on sHTG-associated episodes of AP. METHODS This phase 2b study (NCT04863014) enrolled adults with sHTG and a history of hypertriglyceridemia-associated AP. Eligible patients were randomly assigned to intravenous evinacumab 20 mg/kg or placebo every 4 weeks over a 52-week double-blind treatment period. RESULTS Forty patients were screened; 21 patients received either evinacumab (n = 11) or placebo (n = 10). Twelve (57.1%) patients completed the study. The proportion of patients with ≥1 positively adjudicated AP episode during the 52-week treatment period (primary endpoint) was 27.3% (n = 3) with evinacumab vs 10.0% (n = 1) with placebo. All positively adjudicated AP episodes occurred ≥58 days after the last evinacumab dose, when evinacumab concentrations were mostly near or below the limit of quantitation. The median percentage change in triglycerides from baseline to week 4 was −55.3% with evinacumab vs +1.5% with placebo. By week 16, evinacumab reduced triglycerides by 95.7%; the effect was maintained in 1 patient who received treatment through week 52. Incidence of treatment-emergent adverse events was lower with evinacumab (63.6%) than with placebo (100.0%). CONCLUSION Although the sample size was too small to determine whether evinacumab can prevent AP, the data suggest evinacumab may be efficacious in lowering triglyceride concentrations in patients with sHTG and a history of sHTG-associated AP. Tolerability and safety of evinacumab was consistent with previous studies.