Plozasiran
FDA Drug Information • Also known as: Redemplo
- Brand Names
- Redemplo
- Drug Class
- APOC-III-directed RNA Interaction [EPC], Small Interfering RNA [EPC]
- Route
- SUBCUTANEOUS
- Dosage Form
- INJECTION, SOLUTION
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION REDEMPLO contains plozasiran (present as plozasiran sodium), a small interfering RNA (siRNA) that degrades apolipoprotein C-III ( apoC-III ) mRNA by RNA interference. Plozasiran contains a covalently linked ligand containing three N-acetylgalactosamine (GalNAc) residues to facilitate delivery to hepatocytes. The 2´ positions of the ribose subunits in plozasiran are modified with either fluorine (2´F) or methoxy (2´O-Me) groups. Each strand of plozasiran also includes multiple phosphorothioates. The molecular formula of plozasiran sodium is C 493 H 611 F 11 N 164 Na 43 O 311 P 43 S 7 and its molecular weight is 16,563.98 Da. Plozasiran sodium is freely soluble in water. Plozasiran has the following structural formula: Abbreviations: A = 2’-O-methyladenosine; A = 2’-fluoro(2’-deoxy-2’-fluoro)adenosine; C = 2’-O-methylcytidine; C = 2’-fluorocytidine; G = 2’-O-methylguanosine; G = 2’-fluoroguanosine; I = 2’-O-methylinosine; U = 2’-O-methyluridine; U = 2’-fluorouridine; - (single line) = phosphodiester linkage; = (double line) = phosphorothioate linkage; · (middle dot) depicts base pairing between the two strands REDEMPLO is a sterile, preservative-free, clear, colorless to yellow solution for subcutaneous use in a prefilled syringe. Each syringe contains 0.5 mL of solution containing 25 mg plozasiran (present as 27 mg plozasiran sodium), sodium chloride to adjust tonicity, and water for injection. Chemical Structure
What Is Plozasiran Used For?
1 INDICATIONS AND USAGE REDEMPLO is indicated as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS). REDEMPLO is an apolipoprotein C-III ( apoC-III )-directed small interfering ribonucleic acid (siRNA) 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 REDEMPLO is 25 mg injected subcutaneously once every 3 months. ( 2.1 ) Inject REDEMPLO subcutaneously into the front of the thigh or abdomen. The outer area of the upper arm can 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 REDEMPLO is 25 mg injected subcutaneously once every 3 months. 2.2 Important Administration Instructions Prior to initiation, train patients and/or caregivers on proper preparation and administration of REDEMPLO [see Instructions for Use ] . Adhere to a low-fat diet (less than or equal to 20 grams fat per day) in conjunction with REDEMPLO. Visually inspect the REDEMPLO pre-filled syringe 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. Inject REDEMPLO subcutaneously into the front of the thigh or abdomen. The outer area of the upper arm can be used as an injection site if a healthcare provider or caregiver administers the injection. Do not inject REDEMPLO in an area where the skin is damaged (tender, bruised, red, hard, or cut). Do not inject into areas with scars or stretch marks. If a dose is missed, administer REDEMPLO as soon as possible. Resume dosing every 3 months from the date of the most recently administered dose.
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS Most common adverse reactions in REDEMPLO treated patients (incidence ≥10% of patients treated with REDEMPLO and >5% more frequently than with placebo) are hyperglycemia, headache, nausea, and injection site reaction. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Arrowhead Pharmaceuticals Inc. at 1-844-REDEMPLO (1-844-733-3675), or https://arrowheadpharma.com/safetyreporting, 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 REDEMPLO 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 REDEMPLO was evaluated in 75 patients with FCS enrolled in Trial 1 (NCT05089084) [see Clinical Studies ( 14 )] . In this trial, patients received at least one dose of REDEMPLO 25 mg (N=26) or 50 mg of plozasiran (N=24) and 25 patients received placebo. Plozasiran 50 mg is not an approved dosage regimen for FCS [see Dosage and Administration ( 2.1 )] . Across treatment groups, the mean age was 46 years and 49% of patients were male. Seventy-three percent (73%) of patients were White, 21% were Asian, and 5% were reported as other races; 3% identified as Hispanic or Latino ethnicity. Fifty (50) patients were exposed to REDEMPLO for a median of 11.6 months; 26 patients were treated with REDEMPLO 25 mg every 3 months for a median of 11.8 months. Adverse reactions led to discontinuation of treatment in 3 (6.0%) of REDEMPLO-treated patients and 0% of placebo-treated patients. The reasons for REDEMPLO treatment discontinuation were hyperglycemia and urticaria. Adverse reactions occurring in greater than or equal to 10% of REDEMPLO-treated patients and greater than 5% more frequently than in placebo-treated patients are listed below in Table 1 . Table 1. Adverse Reactions Occurring in Greater than or Equal to 10% of REDEMPLO-treated Patients and Greater than 5% More Frequently than with Placebo in Trial 1 1 Grouped terms composed of several similar terms Adverse Reactions Placebo (N=25) (%) REDEMPLO (N=50) (%) Hyperglycemia 1 2 (8%) 10 (20%) Headache 2 (8%) 8 (16%) Nausea 2 (8%) 7 (14%) Injection site reaction 1 1 (4%) 5 (10%) Laboratory Tests Increase in Glucose: Mean increases from baseline in HbA1c (up to 0.36%) and fasting glucose (up to 9 mg/dL) were observed over time in the 25 mg REDEMPLO group. The incidence of hyperglycemia (defined as adverse events consistent with diabetes mellitus or hyperglycemia, new antidiabetic medication, or laboratory values) was higher in 25 mg REDEMPLO-treated patients without a medical history of diabetes at baseline (40%) compared to placebo-treated patients (20%). Increase in Liver Enzymes: Increases from baseline liver enzymes within the normal range were observed with plozasiran treatment in the FCS population. These increases occurred within the first 3 months of treatment and stabilized. 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 REDEMPLO compared to those treated with placebo [see Clinical Studies ( 14 )] . Despite increases in the LDL-C, the average LDL-C value at Month 12 was less than 50 mg/dL in the 25 mg REDEMPLO group.
Contraindications
4 CONTRAINDICATIONS None. None. ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary There are insufficient data on REDEMPLO use in pregnant women to inform a 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, no adverse drug-related developmental effects were observed in pregnant rats or rabbits with subcutaneous administration of plozasiran during organogenesis up to 23 and 140 times, respectively, the maximum recommended human dose (MRHD) (see Data ) . The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20% respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo-Fetal Risk 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 In an embryo-fetal development study, pregnant rats were administered plozasiran by subcutaneous injection at 0, 5, 15, or 60 mg/kg, or 60 mg/kg rat specific surrogate, once daily during the period of organogenesis (gestational days 6 to 17). There was no evidence of drug-related embryo-fetal toxicity or fetal malformations up to 60 mg/kg plozasiran [23 times the MRHD based on body surface area (BSA)]. At maternally toxic doses there were embryo-fetal toxicities including increases in post-implantation loss and mean number of late resorptions at 60 mg/kg (23 times the MRHD based on BSA), early deliveries, reduced fetal body weight, and fetal skeletal developmental variations at ≥15 mg/kg (6 times the MRHD based on...
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING REDEMPLO injection is a clear and colorless to yellow solution supplied in a single-dose prefilled syringe. Each prefilled syringe of REDEMPLO is filled to deliver 0.5 mL of solution containing 25 mg of plozasiran. REDEMPLO is available in cartons containing one 25 mg single-dose prefilled syringe each (NDC 84141-025-01). Storage Store REDEMPLO refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton, until ready for use. REDEMPLO prefilled syringe can also be kept at room temperature at 20°C to 25°C (68°F to 77°F) in the original carton for up to 30 days. If not used within the 30 days stored at room temperature, discard REDEMPLO.
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.