Tryngolza

Tryngolza (olezarsen) 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). Tryngolza is given as a subcutaneous (under the skin) injection once a month.

Tryngolza works by targeting a specific genetic message (messenger RNA) that instructs the body to produce apolipoprotein C-III (apoC-III), a protein that normally blocks the clearance of triglycerides from the blood. By reducing apoC-III levels, Tryngolza helps the body remove triglycerides more effectively.

Tryngolza (olezarsen) first received FDA approval on December 19, 2024. There is no generic

Tryngolza (olezarsen) is FDA-approved to be used alongside diet for:

• Familial chylomicronemia syndrome (FCS) to reduce triglycerides (TG). Patients should maintain a low-fat diet, consuming 20 g or less of fat per day. FCS is a rare inherited disorder that causes extremely high triglyceride levels.
• 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.

Read the detailed Instructions for Use that comes with your Tryngolza single-dose autoinjector.

• Your healthcare provider will show you and/or your caregiver how to inject Tryngolza the first time.
• Tryngolza 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.
• Tryngolza is injected 1 time each month.
• Tryngolza must be used with a low-fat diet (less than 20 grams of fat each day).

How to Use the Tryngolza Autoinjector

• Remove the autoinjector from the refrigerator 30 minutes before injection (allow to reach room temperature)
• Check expiration date and inspect solution (should be clear to slightly opalescent)
• Clean the injection site with an alcohol swab
• Remove the autoinjector cap just before the injection
• Press firmly against the skin and hold until the injection completes
• Throw away the used autoinjector in a sharps container
• Rotate injection sites with each monthly dose to prevent skin irritation.

Important: Your healthcare provider or pharmacist will demonstrate proper injection technique before you self-administer at home.

Do not use Tryngolza if you have had a serious allergic reaction to olezarsen, Tryngolza, or any of the inactive ingredients in the injection.

Before using Tryngolza, 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.

It is not known if Tryngolza is safe and effective in children and adolescents under 18 years.

Pregnancy

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

Breastfeeding

It is not known if Tryngolza 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 Tryngolza.

Common side effects

The most common side effects of Tryngolza are:

• Injection site reactions (such as redness or pain at the injection site)
• Decreased platelet counts (these are blood cells that help clot blood)
• Joint pain or stiffness.

Serious side effects and warnings

Tryngolza may cause the following serious side effects:

• Allergic Reactions. Tryngolza can cause side effects, including allergic reactions that may be serious. Allergic reactions can include skin redness; red itchy bumps (hives); swelling of the face; chills; or trouble breathing. Stop taking Tryngolza and call your healthcare provider or get emergency help right away if you have any of these symptoms.
• Liver problems: Tryngolza 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 symptomsof 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 Tryngolza. Tell your healthcare provider if you have any side effect that bothers you, or do not go away while taking Tryngolza. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Tryngolza (olezarsen) works by blocking the genetic instructions (mRNA) that tell your liver to produce a protein called Apolipoprotein C-III (apoC-III). ApoC-III slows down a person's ability to clear fat, such as triglycerides, through the liver, resulting in more triglycerides in the blood. Tryngolza binds to apoC-III mRNA, reducing the production of serum apoC-III protein. This leads to increased clearance of plasma triglycerides (TG) and very low-density lipoproteins (VLDLs).

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

Tryngolza for familial chylomicronemia syndrome (FCS)

FDA approval of Tryngolza for FCS was based on the BALANCE clinical trial (NCT04568434), a Phase 3 randomized, placebo-controlled study in 66 adults with FCS. Results included:

• A 43% average reduction in fasting triglycerides at 6 months compared with placebo
• A 57% average reduction in fasting triglycerides at 12 months compared with placebo
• Fewer acute pancreatitis attacks with Tryngolza (1 attack in 1 patient) versus placebo (11 attacks in 7 patients)

Tryngolza for severe hypertriglyceridemia (sHTG)

FDA approval of Tryngolza for sHTG was supported by the Phase 3 CORE (NCT05079919) and CORE2 (NCT05552326) studies. Results included:

• Up to 72% reduction in fasting triglycerides compared with placebo at 6 months, with reductions sustained at 12 months
• Up to 91% decrease in acute pancreatitis episodes compared with placebo
• 86% of patients achieved triglyceride levels below 500 mg/dL at 12 months

Dose of Tryngolza for familial chylomicronemia syndrome (FCS)

• 80 mg subcutaneously once a month
• Administer on the same date each month for consistency.

Dose of Tryngolza for severe hypertriglyceridemia (sHTG)

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

While taking Tryngolza, you must follow a strict low-fat diet of no more than 20 grams of fat per day. This dietary change is essential. Without it, Tryngolza will not work effectively to lower your triglyceride levels.

FCS patients must limit their fat intake to just 20 grams. Most Americans consume 50-150 grams of fat daily.

Foods that exceed or use most of your daily fat allowance:

FCS-Friendly Low-Fat Food Options:

Choose lean proteins and other low-fat choices.

Sample Daily Meal Plan Within 20-Gram Fat Limit

Breakfast (6 grams of fat):

• 1 large egg scrambled = 5 grams
• 1 slice whole wheat toast (dry) = 1 gram
• Fresh berries = 0 grams
• Black coffee or tea = 0 grams

Lunch (5 grams of fat):

• 3 oz grilled skinless chicken breast = 3 grams
• Large salad with non-fat dressing = 0 grams
• 1 cup brown rice = 2 grams
• Steamed vegetables = 0 grams

Dinner (7 grams of fat):

• 4 oz baked white fish = 2 grams
• Sweet potato (no butter) = 0 grams
• Steamed broccoli = 0 grams
• 1 teaspoon olive oil for cooking = 5 grams

Snacks (2 grams of fat):

• Fresh fruit = 0 grams
• Non-fat yogurt = 0 grams
• Vegetables with non-fat dip = 0 grams
• Air-popped popcorn = 2 grams

Total daily fat: 20 grams

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Tryngolza (olezarsen) appears to have a low risk of causing drug-drug interactions. Research has found that Tryngolza:

• Does not inhibit or induce CYP450 enzymes (the main drug-metabolizing enzymes)
• Is not a substrate or inhibitor of key drug transporters (OAT, OCT, OATP, MATE, BCRP, P-gp, BSEP)
• Does not affect the protein binding of other drugs like warfarin and ibuprofen.

Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. See the Tryngolza Prescribing Information for more information.

If you miss a dose of Tryngolza, take the missed dose as soon as possible.

• Then inject Tryngolza 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.
• Stay on your low-fat diet (less than 20 grams of fat each day) while using Tryngolza.

Store Tryngolza in the refrigerator between 36°F and 46°F (2°C and 8°C) in the original carton.

Tryngolza can also be stored at room temperature between 59°F and 86°F (15°C and 30°C) in the original carton for up to 6 weeks.

• Discard if stored at room temperature longer than 6 weeks.

Do not freeze Tryngolza.

• Do not expose the autoinjector to heat.
• Protect from light.

Keep the Tryngolza 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 formulation: Single-dose autoinjector containing 80 mg/0.8 mL.

Tryngolza is distributed by Ionis Pharmaceuticals, Inc., Carlsbad, CA 92010.