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Olezarsen Sodium

FDA Drug Information • Also known as: Tryngolza

Brand Names
Tryngolza
Route
SUBCUTANEOUS
Dosage Form
INJECTION, SOLUTION
Product Type
HUMAN PRESCRIPTION DRUG

Description

11 DESCRIPTION Olezarsen is an ASO directed inhibitor of Apolipoprotein C-III (apoC-III) mRNA, conjugated to a ligand containing three N -acetyl galactosamine (GalNAc) residues to enable delivery of the ASO to hepatocytes. TRYNGOLZA contains olezarsen sodium as the active ingredient. Olezarsen sodium is a white to yellow solid and it is freely soluble in water and in phosphate buffer. The molecular formula of olezarsen sodium is C 296 H 419 N 71 O 154 P 20 S 19 Na 20 and the molecular weight is 9124.48 daltons. The chemical name of olezarsen sodium is DNA, d(P-thio) ([2'- O -(2-methoxyethyl)] rA-[2'- O -(2-methoxyethyl)] rG-[2'- O -(2-methoxyethyl)] m5rC-[2'- O -(2-methoxyethyl)] m5rU-[2'- O -(2-methoxyethyl)] m5rU-m5C-T-T-G-T-m5C-m5C-A-G-m5C-[2'- O -(2-methoxyethyl)] m5rU-[2'- O -(2-methoxyethyl)] m5rU-[2'- O -(2-methoxyethyl)] m5rU-[2'- O -(2-methoxyethyl)] rA-[2'- O -(2-methoxyethyl)]m5rU), 5'-[26-[[2-(acetylamino)-2-deoxy-β-D-galactopyranosyl]oxy]-14,14-bis[[3-[[6-[[2-(acetylamino)-2-deoxy-β-D-galactopyranosyl]oxy]hexyl]amino]-3-oxopropoxy]methyl]-8,12,19-trioxo-16-oxa-7,13,20-triazahexacos-1-yl hydrogen phosphate], sodium salt (1:20). The structure of olezarsen sodium is presented below: TRYNGOLZA is a sterile, preservative-free solution for subcutaneous injection. Each single-dose autoinjector contains 80 mg olezarsen (equivalent to 84 mg of olezarsen sodium) in 0.8 mL of solution. The solution also contains the following 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 between 6.9 to 7.9. Each dose of TRYNGOLZA injection contains 6 mg of phosphorous and 5 mg of sodium. Chemical Structure

What Is Olezarsen Sodium Used For?

1 INDICATIONS AND USAGE TRYNGOLZA is indicated as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS). TRYNGOLZA is an APOC-III -directed antisense oligonucleotide (ASO) indicated as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS). ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION The recommended dosage of TRYNGOLZA is 80 mg administered subcutaneously once monthly. ( 2.1 ) Administer TRYNGOLZA into the abdomen or front of the thigh. The back of the upper arm can also be used as an injection site if a healthcare provider or caregiver administers the injection. ( 2.2 ) 2.1 Recommended Dosage The recommended dosage of TRYNGOLZA is 80 mg administered subcutaneously once monthly [see Dosage and Administration (2.2) ] . 2.2 Administration Instructions Prior to initiation, train patients and/or caregivers on proper preparation and administration of TRYNGOLZA [see Instructions for Use ] . Remove the single-dose autoinjector from the refrigerator 30 minutes prior to the injection and allow to warm to room temperature. Do not use other warming methods. Inspect TRYNGOLZA visually for particulate matter prior to administration. The solution should be clear and colorless to yellow. Do not use if cloudiness, particulate matter, or discoloration is observed prior to administration. Maintain a low-fat diet (≤20g fat per day) in conjunction with TRYNGOLZA. Inject TRYNGOLZA subcutaneously into the abdomen or front of the thigh. The back of the upper arm can also be used as an injection site if a healthcare provider or caregiver administers the injection. Administer TRYNGOLZA as soon as possible after a missed dose. Resume dosing at monthly intervals from the date of the most recently administered dose.

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed elsewhere in the labeling: Hypersensitivity Reactions [ see Warnings and Precautions (5.1) ] Most common adverse reactions (incidence >5% of TRYNGOLZA-treated patients and >3% higher frequency than placebo) were injection site reactions, decreased platelet count, and arthralgia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Ionis Pharmaceuticals Inc. at toll free number 1-833-644-6647 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of TRYNGOLZA cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of TRYNGOLZA was evaluated in 66 patients with FCS enrolled in Trial 1 (NCT #04568434) [see Clinical Studies (14) ] . In this trial, 43 patients received at least one dose of TRYNGOLZA, 50 mg (N=21) or 80 mg (N=22) and 23 patients received placebo. TRYNGOLZA 50 mg is not an approved dosing regimen for FCS [see Dosage and Administration (2.1) ]. Across treatment groups, the mean age was 45 years and 42% of patients were male. Eighty-five percent (85%) of patients were White, 9% were Asian and 6% were reported as other races; 11% identified as Hispanic or Latino ethnicity. Forty-three (43) patients were exposed to TRYNGOLZA for a median of 52 weeks; 22 patients were treated with TRYNGOLZA 80 mg every 4 weeks for a median of 52 weeks. Adverse reactions led to discontinuation of treatment in 7% of TRYNGOLZA-treated patients and 0% of placebo-treated patients. The most common reasons for TRYNGOLZA treatment discontinuation were hypersensitivity reactions. Adverse reactions (>5% of patients treated with TRYNGOLZA and at >3% higher frequency than placebo) are presented in Table 1. Table 1. Adverse Reactions That Occurred in >5% of Patients Treated with TRYNGOLZA and at >3% Higher Frequency than Placebo (Trial 1) Adverse Reaction Grouped terms composed of several similar terms Total TRYNGOLZA (N = 43) Placebo (N = 23) Injection site reactions 8 (19%) 2 (9%) Decreased platelet count 5 (12%) 1 (4%) Arthralgia 4 (9%) 0 Laboratory Tests Decrease in Platelet Count: TRYNGOLZA can cause reductions in platelet count. In Trial 1, the mean platelet count in the TRYNGOLZA 80 mg group was 188,000 mm 3 at baseline, and the mean percent change in platelet count was -10% at Week 53. In comparison, the mean platelet count in the placebo group was 215,000/mm 3 at baseline, and the mean percent change in platelet count was 22% at Week 53. No TRYNGOLZA-treated patient with FCS had a platelet count <50,000/mm 3 . There were no major bleeding events associated with a low platelet count. Overall, the proportion of patients experiencing a bleeding adverse event was similar across the TRYNGOLZA and placebo treatment groups. Increase in Glucose: Small increases in average values in fasting glucose (≤17 mg/dL) and HbA1c (<0.2 percentage points) were observed over time with TRYNGOLZA treatment in the FCS population in Trial 1. The incidence of hyperglycemia (defined as adverse events, new antidiabetic medication, or laboratory values) was higher in olezarsen-treated patients without a medical history of diabetes at baseline (52%) compared to placebo-treated patients (35%). Increase in Liver Enzymes: Increases from baseline in liver enzymes within the normal range were observed with olezarsen treatment in the FCS population. These increases occurred within the first 3 months of treatment and stabilized. Liver enzymes returned towards baseline with discontinuation of olezarsen. Increase in LDL-cholesterol: Increases in low-density lipoprotein cholesterol (LDL-C) and total apolipoprotein B (apoB) were observed in the FCS population treated with TRYNGOLZA compared to those treated with placebo [see Clinical Studies (14) ] . Despite...

Contraindications

4 CONTRAINDICATIONS TRYNGOLZA is contraindicated in patients with a history of serious hypersensitivity to olezarsen or any of the excipients in TRYNGOLZA. Hypersensitivity reactions, including symptoms of bronchospasm, diffuse erythema, facial swelling, urticaria, chills, and myalgias, requiring medical treatment have occurred [see Warnings and Precautions (5.1) ] . History of serious hypersensitivity reactions to olezarsen or any of the excipients in TRYNGOLZA. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary There are no available data on TRYNGOLZA use in pregnant women to inform drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Patients with FCS are at risk for pancreatitis during pregnancy because of defects in lipid metabolism and increased triglyceride levels (see Clinical Considerations ) . In animal reproduction studies conducted with the unconjugated antisense oligonucleotide (lacking GalNAc) in rabbits and mice, no adverse effects on development or pregnancy were observed at doses 21 times or 20 times, respectively, the maximum recommended clinical dose. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20% respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo-Fetal Risk During pregnancy, triglyceride levels increase during the third trimester of pregnancy. In patients with underlying defects in lipid metabolism, such as FCS, severe gestational hypertriglyceridemia may occur, increasing the risk of acute pancreatitis during pregnancy. Data Animal Data Olezarsen was not evaluated for potential effects on embryofetal development (EFD). However, effects of the administration of the unconjugated antisense oligonucleotide (ASO), which shares the same nucleotide sequence but lacks the N-acetyl galactosamine [GalNAc] moiety [see Description (11) ] , were evaluated. In a combined fertility and embryo-fetal development study in mice, the unconjugated ASO was administered to male and female mice by subcutaneous injection at doses of 10.5, 35, and 87.5 mg/kg/week prior to mating and through to the completion of organogenesis (gestation day 15). No adverse developmental outcomes occurred...

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied TRYNGOLZA injection is a sterile, preservative-free, clear, colorless to yellow solution supplied in a single-dose autoinjector. Each autoinjector of TRYNGOLZA is filled to deliver 0.8 mL of solution containing 80 mg of olezarsen. TRYNGOLZA is available in cartons containing one 80 mg single-dose autoinjector each (NDC 71860-101-01). 16.2 Storage and Handling Store the TRYNGOLZA autoinjector in the refrigerator between 2°C and 8°C (36°F and 46°F) in the original carton. Once taken out of the refrigerator, the TRYNGOLZA autoinjector can be stored at room temperature between 15°C and 30°C (59°F and 86°F) in the original carton for up to 6 weeks. If not used within the 6 weeks stored at room temperature, discard TRYNGOLZA. Do not freeze. Do not expose to heat . Protect from light. 16.1 How Supplied TRYNGOLZA injection is a sterile, preservative-free, clear, colorless to yellow solution supplied in a single-dose autoinjector. Each autoinjector of TRYNGOLZA is filled to deliver 0.8 mL of solution containing 80 mg of olezarsen. TRYNGOLZA is available in cartons containing one 80 mg single-dose autoinjector each (NDC 71860-101-01).

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.