Key result
APOC3 inhibitors cut triglycerides up to ~80% and lower acute pancreatitis in chylomicronemia syndromes.
Emerging mechanism-based therapies, particularly APOC3 inhibitors, offer promising targeted approaches to reduce extreme hypertriglyceridemia and the risk of acute pancreatitis in chylomicronemia syndromes.
Supports targeted TG reduction in chylomicronemia; leaves open confirmation of pancreatitis risk reduction in RCTs.
PURPOSE OF REVIEW: Familial chylomicronemia (FCS) and multifactorial or persistent chylomicronemia syndromes (MCS, pCS) are rare, severe disorders characterized by extreme hypertriglyceridemia and a high risk of recurrent, potentially life-threatening acute pancreatitis. Most patients do not achieve adequate triglyceride control with lifestyle interventions or conventional lipid-lowering therapies, leaving them exposed to persistent complications. This review critically examines emerging therapeutic strategies aimed at improving triglyceride control and reducing acute pancreatitis risk. RECENT FINDINGS: Advances targeting key molecular regulators of triglyceride metabolism have shown substantial promise. APOC3 inhibitors, including volanesorsen, olezarsen, and plozasiran, achieve up to 80% reductions in triglycerides and markedly lower AP incidence, with favorable safety profiles. ANGPTL3 inhibition via evinacumab may benefit patients with residual lipoprotein lipase activity, including polygenic or mixed chylomicronemia, and could be used during acute sHTG episodes. Lomitapide, acting independently of LPL, is effective in selected FCS patients but requires careful hepatic monitoring. FGF21 analogs, such as pegozafermin, are in early development and show potential for metabolic dysfunction-associated steatotic liver disease, though their impact on acute pancreatitis prevention remains to be established. SUMMARY: These emerging mechanism-based therapies are reshaping the management of severe hypertriglyceridemia, offering targeted approaches to reduce triglycerides and acute pancreatitis risk. Ongoing studies will clarify long-term safety, durability of response, and optimal patient selection, providing a framework for improved clinical outcomes.
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D’Erasmo et al. (2025) conducted a review in Familial chylomicronemia (FCS) and multifactorial or persistent chylomicronemia syndromes (MCS, pCS). Emerging therapeutic strategies (e.g., APOC3 inhibitors, ANGPTL3 inhibitors) was evaluated on Triglyceride control and acute pancreatitis risk. Emerging mechanism-based therapies, particularly APOC3 inhibitors, achieve up to 80% reductions in triglycerides and markedly lower acute pancreatitis incidence in chylomicronemia syndromes.
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