Efficacy of evinacumab in patients with severe hypertriglyceridemia and a history of severe hypertriglyceridemia-related acute pancreatitis: A phase 2b trial
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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.
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Evinacumab reduces triglyceride levels by 50 to 70% in early-phase trials involving patients with severe or refractory hypertriglyceridemia.
“Evinacumab also reduces triglyceride levels, with observed reductions ranging from 50 to 70% in early-phase trials involving patients with severe or refractory HTG [54–56].”
From Targeting Triglycerides in Cardiovascular Disease Prevention: Evidence, Mechanisms, and Emerging Therapies (2026) · cites this paper as [56]
The Change in lipid/lipoprotein parameters section (page unavailable) reports a 55.3% median triglyceride reduction at week 4 in this phase 2b trial, within the claimed range. But it reports a 95.7% reduction at week 16, and the Introduction reports an 81.7% reduction in an earlier phase 2 study. This source therefore supports triglyceride lowering, but not 50–70% as the range of observed trial reductions. (LLM, conf=0.87)
Experimental — accuracy not yet measuredIn a phase 2b study (NCT04863014) in patients with severe HTG and a history of pancreatitis, evinacumab 20 mg/kg confirmed a substantial median TG decrease of 55% at week 4 and >90% at week 16, together with consistent improvements in non-HDL cholesterol and ApoC-III levels.
“A subsequent phase 2b study (NCT04863014) [109] in patients with severe HTG and a history of pancreatitis confirmed a substantial median TG decrease of 55% at week 4 and > 90% at week 16 with the 20 mg/kg dose, together with consistent improvements in non-HDL cholesterol and ApoC-III levels.”
From Targeting triglycerides for cardiovascular risk reduction (2026) · cites this paper as [109]
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Sorted by citations
Alam, U., Mathai, S. V., Filtz, A., Kuno, T., Badimon, J. J., Sniderman, A. D., Virani, S. S., Toth, P. P., Shapiro, M. D., Lavie, C. J., et al. (2026) · Current Cardiology Reports · doi:10.1007/s11886-025-02337-1 · Cited by 4 · see citing works
Targeting triglycerides for cardiovascular risk reduction
Maiorca, C., Tramontano, D., Di Costanzo, A., & D’Erasmo, L. (2026) · Internal and Emergency Medicine · doi:10.1007/s11739-026-04383-1
- Authors
- Rosenson, R. S., George, R. T., Sanchez, R. J., Zhao, X.-Q., Ponda, M. P., Waldron, A., & Pordy, R.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Regeneron (United States) (US)
- Corresponding author
- Rosenson, Robert S.
- ORCID
- Venue
- Journal of Clinical Lipidology
- Publisher
- Elsevier BV
- Published
- 2025-09
- Volume
- 19
- Issue
- 5
- Pages
- 1223-1233
- ISSN
- 1876-4789 (ISSN-L)
- 1933-2874
- OpenAlex
- W4412968083
- Cited by
- 11
- References
- 8
- Citations by year
- 2026: 8 · 2025: 3
- FWCI
- 10.43
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of clinical lipidology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Regeneron Pharmaceuticals Inc
- Topics
- Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Keywords
- evinacumab, severe hypertriglyceridemia, acute pancreatitis, triglyceride lowering, PCSK9 inhibition, treatment-emergent adverse events, drug safety and tolerability
- MeSH terms
- Acute Disease, Adult, Aged, Antibodies, Monoclonal, Double-Blind Method, Female, Humans, Male, Middle Aged, Pancreatitis, Triglycerides, Hypertriglyceridemia, Treatment Outcome, Antibodies, Monoclonal, Humanized
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