TEGSEDI Solution for injection (2020)

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Akcea Therapeutics, Inc.

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BOXED WARNING SECTION

WARNING: THROMBOCYTOPENIA AND GLOMERULONEPHRITIS Thrombocytopenia: TEGSEDI causes reductions in platelet count that may result in sudden and unpredictable thrombocytopenia, which can ...

1. Indications and Usage

TEGSEDI is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.

2. Dosage and Administration

2.1 Dosing Information The recommended dose of TEGSEDI is 284 mg injected subcutaneously once weekly. For consistency of dosing, patients should be instructed to give the injection on the same day every ...

3. Dosage Forms and Strengths

Injection: 284 mg/1.5 mL clear, colorless to pale yellow solution in a single-dose prefilled syringe.

4. Contraindications

TEGSEDI is contraindicated in patients with: Platelet count below 100 109/L [see Warnings and Precautions (5.1)] History of acute glomerulonephritis caused by TEGSEDI [see Warnings ...

5. Warnings and Precautions

5.1 Thrombocytopenia TEGSEDI causes reductions in platelet count that may result in sudden and unpredictable thrombocytopenia that can be life-threatening. In Study 1 [see Clinical studies (14)] ...

6. Adverse Reactions

The following serious adverse reactions are discussed in greater detail in other sections of the labeling: Thrombocytopenia [see Warnings and Precautions (5.1)] Glomerulonephritis and Renal Toxicity ...

6.1. Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of TEGSEDI cannot be directly compared to rates in clinical trials of other ...

6.2. Immunogenicity

The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. In addition, the observed incidence of antibody (including neutralizing antibody) positivity in ...

7. Drug Interactions

7.1 Antiplatelet Drugs or Anticoagulant Medications Because of the risk of thrombocytopenia, caution should be used when using antiplatelet drugs (e.g., adenosine, clopidogrel, prasugrel, ticagrelor, or ...

8.1. Pregnancy

Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to TEGSEDI during pregnancy. Health care providers are encouraged to register patients ...

8.2. Lactation

Risk Summary There is no information regarding the presence of TEGSEDI in human milk, the effects on the breast-fed infant, or the effects on milk production. A study in lactating mice has shown excretion ...

8.4. Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

8.5. Geriatric Use

Clinical studies of TEGSEDI included 69 patients (45%) aged 65 and over. No differences in pharmacokinetics or effectiveness were observed between these patients and younger patients. Patients 65 years ...

8.6. Renal Impairment

No dose adjustment is necessary in patients with mild to moderate renal impairment (estimated glomerular filtration rate [eGFR] ≥30 to <90 mL/min/1.73 m²) [see Clinical Pharmacology (12.3)]. TEGSEDI ...

8.7. Hepatic Impairment

No dose adjustment is necessary in patients with mild hepatic impairment [see Clinical Pharmacology (12.3)]. TEGSEDI has not been studied in patients with other degrees of hepatic impairment. ...

11. Description

Inotersen is an antisense oligonucleotide (ASO) inhibitor of human transthyretin (TTR) protein synthesis. TEGSEDI contains inotersen sodium as the active ingredient. Inotersen sodium is a white to pale ...

12.1. Mechanism of Action

Inotersen is an antisense oligonucleotide that causes degradation of mutant and wild-type TTR mRNA through binding to the TTR mRNA, which results in a reduction of serum TTR protein and TTR protein deposits ...

12.2. Pharmacodynamics

The pharmacodynamic effects of TEGSEDI were evaluated in hATTR amyloidosis patients treated with 284 mg TEGSEDI via subcutaneous injection once weekly. With repeat dosing, the mean percent decreases from ...

12.3. Pharmacokinetics

Following subcutaneous administration, systemic exposure to inotersen increased in a dose-proportional manner over the range of 150-400 mg of inotersen sodium salt. At the recommended TEGSEDI dosing regimen ...

13.1. Carcinogenesis, Mutagenesis, Impairment of Fertility

In a 26-week carcinogenicity study in transgenic (TgRasH2) mice, weekly subcutaneous administration of inotersen (0, 10, 30, or 80 mg/kg) or a rodent-specific (pharmacologically active) surrogate (30 mg/kg) ...

14. Clinical Studies

The efficacy of TEGSEDI was demonstrated in a randomized, double-blind, placebo-controlled, multicenter clinical trial in adult patients with polyneuropathy caused by hATTR amyloidosis (Study 1; NCT 01737398). ...

16.1. How Supplied

TEGSEDI is a clear, colorless to pale yellow solution supplied in a single-dose, prefilled syringe with a SSD. Each prefilled syringe of TEGSEDI is filled to deliver 1.5 mL of solution containing 284 mg ...

17. Patient Counseling Information

Advise the patient and caregiver to read the FDA-approved patient labeling (Medication Guide and Instructions for Use). Thrombocytopenia Inform patients that TEGSEDI can cause reductions in platelet count ...