Triglycerides are the most common fat (lipid) in your blood. If your body cannot break them down, triglyceride levels can build up, which can put stress on your heart, blood vessels, liver, and pancreas.
Tryngolza (olezarsen) is a once-monthly injection that is used to help lower the levels of triglycerides in the blood and lower the risk of acute pancreatitis in people with severe hypertriglyceridemia (very high triglycerides). Tryngolza is used along with diet and lifestyle changes.
What Is Severe Hypertriglyceridemia?
Severe hypertriglyceridemia (sHTG) is when you have very high levels of triglycerides, a type of fat your body uses for energy. Triglycerides are common in your blood. Your body uses them to store energy from foods, such as oils, butter, and animal fats. Triglycerides can also be made in the liver, especially with high-carbohydrate foods. If your body cannot break down and clear triglycerides, they can build up over time. High levels raise the risk of heart disease and acute pancreatitis. sHTG can be caused by genetics plus other factors such as obesity, diabetes, certain medicines, and alcohol use.
Triglyceride levels are measured by a blood test, called a lipid panel. In sHTG, triglycerides are over 500 milligrams/deciliter (mg/dL). Treatment for sHTG depends on how high your level is and whether you have any medical history of heart disease or pancreatitis. If your level is around 1,000 mg/dL or you have had pancreatitis, your health care provider may want to lower your triglyceride level quickly.
Treatment can be a combination of dietary changes and a triglyceride-lowering medicine. Diet changes may include eating foods with fewer carbohydrates and less saturated fats, drinking less alcohol, and eating more fish. Common triglyceride-lowering medicines, such as atorvastatin or fenofibrate, can lower triglyceride levels but have not been shown to lower the risk of acute pancreatitis. Tryngolza has been shown to lower triglyceride levels in people with sHTG, and it may also help lower the risk of acute pancreatitis.
How Does Tryngolza Work for Severe Hypertriglyceridemia?
Tryngolza helps your body break down and clear fats from the blood, which lowers triglyceride levels. It targets a protein known as apolipoprotein C-III (APOC-III). APOC-III slows down the removal of triglycerides from the blood. Tryngolza works by lowering the amount of APOC-III, which helps your body break down and remove triglycerides. This lowers the triglyceride levels and lowers the risk of acute pancreatitis.
How Was Tryngolza Studied for Severe Hypertriglyceridemia?
The FDA approved Tryngolza for sHTG based on two studies that showed how well it works and how safe it is to use. These studies were called CORE-TIMI 72a and CORE2-TIMI 72b.
The combined studies included more than 1,000 people diagnosed with sHTG. Key characteristics of the participants included:
- Everyone was at least 18 years old and had triglyceride levels greater than 500 mg/dL.
- Most people in the studies were White (88.4%), 5.4% were Asian, and 2.1% were Black; 12.3% identified as Hispanic or Latino.
- At the start of the study, the average (median) triglyceride level was 793 mg/dL.
- Almost all of the people were taking at least one lipid-lowering medicine.
- People could not join the studies if they had a genetic condition called familial chylomicronemia, acute pancreatitis within four weeks before screening, uncontrolled diabetes, or kidney disease.
The table below provides some traits of the people in each study.
Traits in CORE-TIMI 72a and CORE2-TIMI 72b Studies
CORE-TIMI 72a | CORE2-TIMI 72b | |
|---|---|---|
| Average Age | 54 | 55 |
| Female | 20% to 26% | 18% to 26% |
Race: White Black Asian |
93% 1% to 3% 1% to 2% |
77% to 84% 1% to 3% 9% to 11% |
| Hispanic or Latino | 3% to 5% | 21% to 24% |
| Diabetes mellitus | 54% to 62% | 68% |
| History of Pancreatitis | 21% to 24% | 11% to 14% |
| Average triglyceride level | 810 to 845 mg/dL | 730 to 762 mg/dL |
Everyone was randomly assigned to receive Tryngolza (50 mg or 80 mg) or a placebo (a fake treatment that has no medicine). But no one knew if they were using an injection with medicine or a placebo. People received an injection under the skin (subcutaneously) every four weeks for a total of 48 weeks or about 12 months. In both studies, the effect of Tryngolza was measured by the percentage change in triglyceride levels at six months.
What Are the Main Benefits of Tryngolza for sHTG Based on Studies?
After six months, people who received Tryngolza saw about a 72% drop in their triglyceride levels. Lowering triglyceride levels is important because very high levels can increase the risk of acute pancreatitis. In the studies, a secondary analysis showed a lower rate of acute pancreatitis in people who received Tryngolza than in those who received placebo.
Average Triglyceride Level Reduction in CORE-TIMI 72a and CORE2-TIMI 72b Studies
Tryngolza 50 mg | Tryngolza 80 mg | Placebo | |
|---|---|---|---|
| CORE-TIMI 72a | 63.4% | 72.7% | 0.4% |
| CORE2-TIMI 72b | 62.8% | 68.1% | 13.6% |
Your results may differ from what was seen in clinical studies.
How Long Until I See the Full Effects of Tryngolza?
In the studies, people began to see improvements in their triglycerides right away, with the largest change happening in the first three months. The benefits continued through 12 months.
How Do I Prevent and Manage Tryngolza Side Effects?
The most common side effects of Tryngolza are injection site reactions and increased liver enzymes. Call your health care provider if you have the following symptoms and they bother you or do not go away.
Injection site reactions: Some people have skin reactions at or around the area where Tryngolza is injected. In studies, around 15% of people had these reactions. Symptoms at or near the injection site may include:
- Pain
- Itching
- Swelling
- Redness or discoloration
- Bruising
These symptoms are usually temporary and go away on their own. Tips to prevent or manage injection site reactions include:
- Review the instructions that come with your medicine or see the guide on the drugmaker’s website.
- Be sure to rotate the injection site each day – don’t use the same spot over and over.
- Ask your health care provider if it’s OK to use a cool compress on the area or if an over-the-counter (OTC) pain reliever or anti-itch medicine may help.
Let your health care provider know if symptoms persist or feel severe. They may want to review proper injection techniques with you or suggest other ways to manage your symptoms.
Liver enzyme changes: Tryngolza may cause your liver enzymes or fat stored in your liver to increase. Your health care provider may check your liver function with a blood test before and during your treatment due to the risk of side effects. Liver function test (LFT) includes a group of tests that check to see if your liver is damaged. Call your health care provider right away if you have any of the following symptoms of liver damage:
- Nausea or vomiting
- Stomach or belly pain
- Fever
- Weakness or unusual tiredness
- Itching
- Loss of appetite
- Light-colored poop
- Dark-colored urine (pee)
- Your skin or the whites of your eyes turning yellowish in color (also called jaundice)
These are not all of the possible side effects. Talk to your health care provider if you are having symptoms that bother you. In the U.S., you can report side effects to the FDA at www.fda.gov/medwatch or by calling 800-FDA-1088 (800-332-1088). In Canada, you can report side effects to Health Canada at www.health.gc.ca/medeffect or by calling 866-234-2345.
Getting a Specialty Medicine: What to Expect
Tryngolza is a specialty medicine, a high-cost medication that is prescribed for rare, complex, or chronic diseases. It may require a different process than picking up a regular prescription at your local pharmacy. The drugmaker may have a program to help support the process, or your insurance company may require a specific pharmacy to fill the prescription. Your health care provider will work with you, your insurance company, and/or the manufacturer to help you get the medicine.
Here are some differences that you may expect:
Insurance approval. Your insurance may require approval for covering this medicine, also called prior authorization. The insurance company reviews the prescription from your health care provider to make sure it is covered and determines the process that needs to be followed.
Specialty pharmacy. You may need to use a specialty pharmacy to get your medicine each month. The pharmacist works with your health care provider, insurance company, and/or drugmaker to help you get started, learn how to use and store the medicine, monitor side effects, and manage refills.
Cost assistance. The cost of Tryngolza can vary depending on your insurance status. Some insurance plans may cover this medicine, while some may not. Financial help may be available. The pharmacy will work with you and your insurance to check if there is a savings program that can help lower the cost if you qualify. You can visit this website for more information.
What Else Should I Know About Tryngolza?
It is unknown if drinking alcohol will affect Tryngolza. However, alcohol may raise your triglyceride levels. It is best to limit the amount of alcohol you drink.
