A proven mechanism of action that lowers apolipoprotein C-III (apoC-III) at its source1
TRYNGOLZA is a GalNAc-conjugated antisense oligonucleotide that enables targeted delivery to the liver, where apoC-III, a key regulator of triglyceride metabolism, is generated.1-3
TRYNGOLZA is designed to work by:
STEP 1
Targeting hepatocytes
GalNAc enables targeted delivery to the liver, where apoC-III is generated.1,2
STEP 2
Selectively binding to apoC-III mRNA
In the hepatocyte, TRYNGOLZA directly and selectively binds to apoC-III mRNA.1,3
STEP 3
Degrading apoC-III mRNA
TRYNGOLZA induces RNase cleavage of apoC-III mRNA, leading to its degradation.1-3
This mechanism leads to reduced serum apoC-III and increased clearance of plasma triglycerides, very low-density lipoprotein (VLDL), and chylomicrons.1,3
See how TRYNGOLZA works
See how TRYNGOLZA works
How TRYNGOLZA works. Introducing the validated antisense oligonucleotide, or ASO, technology that lowers apolipoprotein C-III at its source
Severe hypertriglyceridemia, or sHTG, is characterized by persistently elevated fasting triglyceride levels at or above 500 mg/dL.
Despite available lipid-lowering therapies, many adults continue to have triglyceride levels above 500 mg/dL, placing them at significantly increased risk of acute pancreatitis.
TRYNGOLZA is the first and only FDA-approved therapy to reduce triglycerides and the risk of acute pancreatitis in adults with severe hypertriglyceridemia, as an adjunct to diet.
Today, we will explore the role of apolipoprotein C-III in triglyceride metabolism and the targeted mechanism of action of TRYNGOLZA.
The role of apoC-III in sHTG
Our understanding of the pathology of sHTG begins with triglyceride-rich lipoprotein, or TRL, metabolism.
sHTG results from the impaired metabolism of TRLs, such as chylomicrons and very low-density lipoproteins, or VLDL.
Apolipoprotein C-III, or apoC-III, regulates TRL metabolism and breakdown by inhibiting lipoprotein lipase, or LPL, and LPL-independent pathways such as hepatic clearance.
When elevated apoC-III levels impair TRL metabolism, patients experience persistently elevated triglycerides above 500 mg/dL, raising the risk of acute pancreatitis, pancreatic necrosis, organ failure, and type 3c diabetes, making effective and substantial triglyceride lowering imperative.
TRYNGOLZA: a highly targeted therapy
TRYNGOLZA is a GaINAc-conjugated antisense oligonucleotide, or ASO, that inhibits the production of apoC-III, a key regulator of TRL metabolism and hepatic clearance.
The conjugation of GalNAc to the ASO enables targeted delivery to the liver, where apoC-III messenger RNA, or mRNA, is generated.
GalNAc binds to the asialoglycoprotein receptor and allows TRYNGOLZA to enter the hepatocyte.
In the hepatocyte, TRYNGOLZA directly and selectively binds to apoC-III mRNA and induces RNase cleavage of apoC-III mRNA, leading to its degradation.
This results in a decrease in serum apoC-III protein levels, lower plasma triglyceride levels, and fewer acute pancreatitis events.
TRYNGOLZA: a targeted approach designed to help adults with severe hypertriglyceridemia bring their triglycerides out of the danger zone and reduce the risk of acute pancreatitis, along with diet.
Pharmacodynamics: TRYNGOLZA every 4 weeks decreased fasting apoC-III1
Sustained reductions were observed in fasting apoC-III from baseline over 1 year.1
*Trial 2 and Trial 3 in the full Prescribing Information.1