Volanesorsen, an antisense oligonucleotide inhibitor of apolipoprotein C3, reduces triglyceride levels by 70-80% and reduces rates of pancreatitis in familial chylomicronemia syndrome.
Does volanesorsen reduce triglyceride levels and pancreatitis in patients with familial chylomicronaemia syndrome or familial partial lipodystrophy?
Volanesorsen, an apoC3 inhibitor, offers a promising targeted therapy for reducing severe hypertriglyceridemia and associated pancreatitis in rare genetic lipid disorders like FCS and FPLD.
Severe hypertriglyceridaemia is associated with pancreatitis and chronic pancreatitis-induced diabetes. Familial chylomicronaemia syndrome (FCS) is a rare autosomal recessive disorder of lipid metabolism characterised by high levels of triglycerides (TGs) due to failure of chylomicron clearance. It causes repeated episodes of severe abdominal pain, fatigue and attacks of acute pancreatitis. There are few current options for its long-term management. The only universal long-term therapy is restriction of total dietary fat intake to <10-15% of daily calories (15 to 20g per day). Many patients have been treated with fibrates and statins with a variable response, but many remain susceptible to pancreatitis. Other genetic syndromes associated with hypertriglyceridaemia include familial partial lipodystrophy (FPLD). Targeting apolipoprotein C3 (apoC3) offers the ability to increase clearance of chylomicrons and other triglyceride-rich lipoproteins. Volanesorsen is an antisense oligonucleotide (ASO) inhibitor of apoC3, which reduces TG levels by 70-80% which has been shown also to reduce rates of pancreatitis and improve well-being in FCS and reduce TGs and improve insulin resistance in FPLD. It is now undergoing licensing and payer reviews. Further developments of antisense technology including small interfering RNA therapy to apoC3 as well as other approaches to modulating triglycerides are in development for this rare disorder.
Esan et al. (Wed,) conducted a review in Familial Chylomicronemia Syndrome or Hypertriglyceridaemia. Volanesorsen was evaluated on Triglyceride levels. Volanesorsen, an antisense oligonucleotide inhibitor of apolipoprotein C3, reduces triglyceride levels by 70-80% and reduces rates of pancreatitis in familial chylomicronemia syndrome.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: