FDA Approves Olezarsen as First Treatment to Reduce Pancreatitis Risk in Adults with Hypertriglyceridemia

The FDA approved olezarsen (Tryngolza) because of its ability to reduce triglycerides and acute pancreatitis risk in adult patients with severe hypertriglyceridemia when used with a diet, according to an FDA release.¹ Injected subcutaneously, with results reported from 2 randomized controlled trials, olezarsen will become the first treatment for pancreatitis reduction across this patient population.

“Severe hypertriglyceridemia is a serious condition, defined by fasting triglyceride levels of at least 500 mg/dL,” according to the agency’s release. “Guidelines recommend lowering triglycerides when levels are higher than 500 mg/dL to reduce the risk of acute pancreatitis—sudden inflammation of the pancreas that can be serious or life-threatening.”

The clinical significance of this approval stems from the inherent dangers of triglyceride-rich lipoproteins, which participate causally in both atherosclerotic cardiovascular disease and systemic low-grade inflammation. Although ethanol and gallstones remain the primary drivers of acute pancreatitis, hypertriglyceridemia is the third leading cause, responsible for up to 25% of cases overall and as many as 50% during pregnancy.^2,3

READ MORE: How Pharmacists Are Leading the Functional Gut Health Revolution

The pathogenesis of this condition involves the interaction of high triglyceride levels with pancreatic lipase, which breaks down these fats into toxic-free fatty acids that cause direct cellular damage to the organ. Additionally, elevated chylomicron levels can increase plasma viscosity, leading to stasis and hypoxia in the pancreatic capillaries.³

Pharmacists must also be aware that extremely high levels of plasma triglycerides can interfere with diagnostic assays for pancreatic enzymes, potentially resulting in falsely low lipase and amylase readings that may delay diagnosis.

The Historical Management of Hypertriglyceridemia: Pancreatitis Reduction

Historically, the foundation of management for these patients has been aggressive lifestyle therapy, as diet and exercise have synergistic effects that can lower triglycerides by up to 70% in some cases. However, many patients, especially those with genetic disorders like familial chylomicronemia syndrome, remain refractory to standard interventions like fibrates, niacin, or omega-3 fatty acids.^1-4

For instance, despite high-dose icosapent ethyl showing promise in reducing cardiovascular events in trials like REDUCE-IT, that and other traditional agents have not definitively demonstrated a reduction in pancreatitis risk in their primary clinical trials. In contrast, the efficacy of olezarsen was established through 2 randomized, double-blind, placebo-controlled trials involving over 1000 adults with an average baseline triglyceride level of 1116 mg/dL.^1,2,4

These trials demonstrated that an 80 mg dose of olezarsen could reduce triglycerides by up to 72%, successfully showing a statistically significant decrease in acute pancreatitis episodes compared with placebo.¹

The pharmacological mechanism of olezarsen involves inhibiting the production of apolipoprotein C-III (Apo C-III) by binding to its mRNA. This is particularly effective because Apo C-III naturally inhibits the activity of lipoprotein lipase and interferes with the hepatic uptake of triglyceride-rich lipoproteins.^3,4

By reducing these levels, olezarsen accelerates the clearance of fats from the blood. This medication represents a technological evolution from earlier antisense oligonucleotides like volanesorsen, which was not approved in the US due to concerns over significantly low platelet levels.

Olezarsen utilizes a GalNAc3 conjugation that allows for lower, once-monthly dosing and minimizes the systemic adverse effects seen with its predecessors.^3,4

What This Approval Means for Pharmacists

For pharmacists, the approval of olezarsen offers an opportunity for enhanced patient monitoring and education. Beyond managing the monthly subcutaneous injections, pharmacists are in a unique position to screen for secondary factors that may worsen hypertriglyceridemia, including poorly controlled diabetes, hypothyroidism, or the use of medications such as atypical antipsychotics, beta-blockers, and oral estrogens.^2,3

Counseling should also focus on safety, particularly regarding the risk of liver enzyme increases and injection site reactions. Providers should consider liver enzyme testing before starting the medication or increasing the dose and instruct patients on the signs of potential allergic reactions, such as hives or facial swelling.¹

The long-term management of these patients is essential, as recurrent acute flares can lead to chronic pancreatitis, which is characterized by permanent loss of endocrine and exocrine function and chronic abdominal pain. Pharmacists must be prepared to manage patients transitioning from acute care to chronic disease management, where long-standing inflammation can lead to complications such as pseudocysts, malabsorption, and steatorrhea.^3,5

The approval of olezarsen provides a much-needed intervention for a vulnerable patient population, and pharmacists will be at the forefront of its successful implementation.^1,5

“Tryngolza received Priority Review and Breakthrough Therapy designations for this indication,” concluded the authors of the release.¹ “The approval was granted to Ionis Pharmaceuticals.”

READ MORE: Digestive Health Resource Center

REFERENCES

1. Notable approval: FDA approves first treatment shown to reduce the risk of acute pancreatitis in adults with severe hypertriglyceridemia. June 24, 2026. Accessed June 24, 2026. News Release. FDA.

2. Clinical feature: therapies for treating hypertriglyceridemia. National Lipid Association. 2022. Accessed June 24, 2026. https://www.lipid.org/lipid-spin/spring-2022/clinical-feature-therapies-treating-hypertriglyceridemia

3. Feingold KR. Pancreatitis secondary to hypertriglyceridemia. [Updated 2025 Sep 24]. In: Feingold KR, Adler RA, Ahmed SF, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279082/

4. Feingold KR. Triglyceride lowering drugs. [Updated 2026 Apr 23]. In: Feingold KR, Adler RA, Ahmed SF, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK425699/

5. Edwards C, Nguyen C, Brown SA, et al. Caring for patients with chronic pancreatitis. US Pharmacist. December 16, 2022. Accessed June 24, 2026. https://www.uspharmacist.com/article/caring-for-patients-with-chronic-pancreatitis