Olezarsen

Olezarsen (Tryngolza) is used along with diet to reduce triglycerides (fats in the blood) in adults with familial chylomicronemia syndrome (FCS) and to reduce triglycerides and the risk of acute pancreatitis in adults with severe hypertriglyceridemia (sHTG). Olezarsen is given as a subcutaneous (under-the-skin) injection once a month using a single-dose auto-injector.

Tryngolza (olezarsen) was first approved by the FDA on December 19, 2024, for the treatment of familial chylomicronemia syndrome (FCS). On June 24, 2026, the approval was expanded to include adults with severe hypertriglyceridemia. Tryngolza is manufactured by Ionis Pharmaceuticals. No generic version is currently available.

Olezarsen is FDA-approved to be used alongside diet for:

• Familial chylomicronemia syndrome (FCS) to reduce triglyceride l(TG) levels. Patients should maintain a low-fat diet consuming 20 g or less of fat per day.
• Severe hypertriglyceridemia (sHTG) with triglycerides of 500 mg/dL or higher, to reduce TG and reduce the risk of acute pancreatitis, a serious and painful inflammation of the pancreas that can be triggered by very high triglyceride levels.

Olezarsen works by targeting and lowering the amount of apoC-III, a protein found in the blood that plays a crucial role in triglyceride metabolism.

• The liver naturally produces apoC-III to help break down triglycerides, but Olezarsen interferes with this process by destroying the messenger RNA (mRNA) that contains instructions for making the protein.
• When the medication successfully reduces apoC-III levels in the blood, it enhances the body's natural ability to clear out certain types of fats, including triglycerides and very low-density lipoproteins (VLDL), from the bloodstream.

Olezarsen belongs to the drug class called APOC-III-directed antisense oligonucleotides (ASO).

Read the detailed Instructions for Use that come with the Tryngolza (olezarsen) Package Insert for your single-dose autoinjector.

Your healthcare provider will show you and/or your caregiver how to inject this medicine the first time.

• Olezarsen is injected under your skin (subcutaneous use) in your stomach area (abdomen) or the front of your upper legs (thighs). Only a healthcare provider or caregiver may give you an injection in the back of your upper arm.
• Olezarsen should be injected 1 time each month.

Stay on your low-fat diet; patients using olezarsen for FCS should eat less than 20 grams of fat each day.

Dietary restrictions with olezarsen

Olezarsen requires patients to follow a strict low-fat diet, limited to just 20 grams of fat per day. This requires medical supervision and often consultation with a dietitian.

Common foods and their fat content:

• One tablespoon olive oil (14g fat)
• One medium avocado (21g fat - exceeds daily limit)
• One ounce of almonds (14g fat)
• One tablespoon butter (12g fat)
• Two eggs (10g fat)
• Three ounces of skinless chicken breast (3g fat)
• One cheese slice (6g fat).

A sample daily meal plan staying within the 20g limit:

• 1-2 teaspoons cooking oil (5-10g fat)
• One skinless chicken breast (3g fat)
• One egg (5g fat)
• Small amounts of other foods for the remaining fat allowance.

Do not use this medicine if you have had a serious allergic reaction to olezarsen, Tryngolza, or any of the inactive ingredients in the injection (see the ingredient list below).

Before using olezarsen, tell your healthcare provider about all of your medical conditions, including if you:

• are pregnant or plan to become pregnant
• are breastfeeding or plan to breastfeed.

Pregnancy

It is not known if olezarsen can harm your unborn baby. Tell your healthcare provider if you become pregnant while using this medicine.

Breastfeeding

It is not known if olezarsen passes into your breast milk and if it can harm your baby. Talk to your healthcare provider about the best way to feed your baby while using this medicine.

Common side effects of olezarsen include injection site reactions like redness and pain, lower platelet counts (which may affect blood clotting), and joint pain and stiffness.

It is not known if this medicine is safe and effective in children.

Serious side effects and warnings

Olezarsen may cause an allergic reaction that could be serious. Allergic reactions can include redness of the skin, red itchy bumps (hives), swelling of the face, chills or trouble breathing. Stop taking olezarsen and call your healthcare provider or get emergency help right away if you have any of these symptoms.

Liver problems: Olezarsen can cause increases in liver enzymes and fat stored inside the liver.Your healthcare provider may do liver tests before you start taking Tryngolza or if there is an increase in your dose. Tell your healthcare provider right away if you have the following symptoms of liver problems:

• feeling tired or weak loss of appetite right upper stomach discomfort dark colored urine yellowing of the skin and eyes.

These are not all the possible side effects of olezarsen. Tell your healthcare provider if you have any side effect that bothers you or that does not go away while taking this treatment. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Dose of olezarsen for FCS

• 80 mg administered subcutaneously (under the skin) once monthly.

Dose of olezarsen for sHTG

• 50 mg administered subcutaneously (under the skin) once monthly.
• For patients with sHTG who tolerate the 50 mg dosage and additional TG reductionis clinically indicated, the dosage may be increased to 80 mg injected subcutaneously once monthly.

See the Tryngolza (olezarsen) Prescribing Information for more detailed dosing instructions.

If you miss a dose of olezarsen, take the missed dose as soon as possible. Then inject olezarsen 1 month from the date of your last dose to get back on a monthly dosing schedule. If you have questions about your dosing schedule, ask your healthcare provider.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

Store the olezarsen autoinjector in the refrigerator between 36°F to 46°F (2°C to 8°C) in the original carton.

• Olezarsen can also be stored at room temperature between 59°F to 86°F (15°C to 30°C) in the original carton for up to 6 weeks.
• Do not let this medicine reach temperatures above 86°F (30°C).
• Throw away the autoinjector if kept at room temperature longer than 6 weeks.
• Do not freeze.
• Do not expose the olezarsen autoinjector to heat.
• Protect from light.

Keep the autoinjector in the carton until ready to use.

• Do not store the autoinjector with the clear cap removed.

Keep out of the reach of children.

Active ingredient: olezarsen sodium.

Inactive ingredients: disodium hydrogen phosphate, sodium chloride, sodium dihydrogen phosphate to maintain pH and provide tonicity and water for injection. The solution may include hydrochloric acid and/or sodium hydroxide for pH adjustment.

Available as a single-dose autoinjector 50 mg/0.8 mL and 80 mg/0.8 mL

Olezarsen is made by Ionis Pharmaceuticals Inc. under the brand name Tryngolza. Ionis’s headquarters are in Carlsbad, California. Other notable drugs by Ionis include:

Qalsody for amyotrophic lateral sclerosis (ALS)

Spinraza for spinal muscular atrophy (SMA)

Tegsedi for hereditary transthyretin-mediated amyloidosis (hATTR)

Wainua for polyneuropathy of hATTR.