Severe Hypertriglyceridemia (defined as serum triglyceride levels of ) affects approximately 1% of the population and sharply increases the risk of developing life-threatening acute pancreatitis. Traditional therapies (including fibrates and omega-3s) only slightly reduce triglyceride levels, and their effect against pancreatitis is unconfirmed. According to recent research, olezarsen has the potential to radically change the management of lipid disorders.
The mechanism of action of olezarsen involves reducing the concentration of apolipoprotein C-III (ApoC-III), which improves the body’s clearance of triglycerides. Two international Phase 3 clinical trials (CORE-TIMI 72a and CORE2-TIMI 72b) were conducted over 12 months to evaluate the efficacy and safety of oleclarsene. More than 1,000 patients (with severe hypertriglyceridemia) from many countries worldwide participated in these randomized, placebo-controlled trials. The main focus of the research was lowering triglyceride levels and preventing cases of acute pancreatitis. Participants were randomly divided into groups that received or of olezarsen, or a placebo, once a month as a subcutaneous injection.
Study Results:
Compared to the placebo group, triglyceride levels were reduced by 72% at 6 months of treatment and remained sustained for the entire 12-month follow-up period. Furthermore, olezarsen also lowered the incidence of pancreatitis by 85%. Patients in the high-risk group, who had extremely high initial triglyceride concentrations and a history of pancreatitis, experienced the most positive results.
In addition to affecting triglycerides, olezarsen also improved the profile of other atherogenic lipids (specifically, triglyceride-rich lipoproteins and non-HDL cholesterol), although LDL cholesterol levels increased slightly. Side effects such as an increase in liver enzyme activity and a decrease in platelets were noted, which were associated with the high dose. Magnetic resonance imaging also showed an increase in the fatty fraction in the liver (dose-dependent), although its clinical significance requires further study. Importantly, the frequency of Serious Adverse Events (SAE) did not differ between the therapeutic and placebo groups.
These studies represent a significant achievement for patients with severe hypertriglyceridemia, who have limited treatment options and a high risk of pancreatitis. Research is ongoing to confirm long-term safety and efficacy. The drug’s impact on markers related to glycemic control and liver function also needs to be studied.
Source: NEJM
