Overview
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.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Olezarsen is an ASO-GalNAc 3 conjugate that binds to apoC-III mRNA leading to mRNA degradation and resulting in a reduction of serum apoC-III protein. Reduction of apoC-III protein leads to increased clearance of plasma TG and VLDL. 12.2 Pharmacodynamics Fasting apoC-III Olezarsen decreased fasting apoC-III following administration of TRYNGOLZA 80 mg dosage every 4 weeks to patients with FCS [See Clinical Studies (14) ] . The placebo-corrected percent change in fasting apoC-III from baseline was -57% at 1 month, -69% at 3 months, -72% at 6 months, and -80% at 12 months. Cardiac Electrophysiology At a dose 1.5-times the maximum approved recommended dosage, TRYNGOLZA does not prolong the QT interval to any clinically relevant extent. 12.
Indications
- 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 )
Common Doses
- 80 mg
- 20 g
Dosage
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.
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 )
Side Effects
- 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.
Interactions
- No major interactions listed on the FDA label. Always consult a healthcare professional.