Amvuttra (vutrisiran sodium)

Vutrisiran, a small interfering RNA (siRNA) that targets transthyretin (TTR) messenger RNA (mRNA), is a TTR silencer.

Vutrisiran is a double-stranded small interfering RNA (siRNA)-N-acetylgalactosamine (GalNAc) conjugate. The vutrisiran siRNA is directed to the liver, the primary site of TTR synthesis, by conjugation to a triantennary GalNAc ligand that binds to the asialoglycoprotein receptor expressed on the surface of hepatocytes. The enhanced stabilization chemistry design of the vutrisiran siRNA-GalNAc conjugate results in increased potency and high metabolic stability allowing for administration once every 3 months by subcutaneous injection.

Vutrisiran-mediated degradation of mutant and wild-type TTR mRNA through RNA interference results in a reduction of serum TTR protein and TTR protein deposits in tissues. Following administration of vutrisiran 25 mg subcutaneously every 3 months in patients with hereditary transthyretin amyloidosis (ATTR), mean serum TTR at steady state was reduced by 83%. Following a single 25-mg dose, a maximum TTR reduction was reached at 6 weeks with TTR reduction maintained for 90 days.

Following single-dose subcutaneous administration of vutrisiran at doses of 5-300 mg (0.2-12 times the recommended dose), peak concentrations increased in a dose-proportional manner, while AUC increased in slightly more than a dose-proportional manner. No accumulation of vutrisiran was observed in plasma following repeated subcutaneous doses of vutrisiran 25 mg once every 3 months in patients with hereditary ATTR. Peak vutrisiran concentrations were reached a median of 4 hours following a single 25-mg dose in healthy subjects.

Vutrisiran distributes primarily to the liver following subcutaneous administration. Vutrisiran is approximately 80% bound to plasma proteins. Protein binding of the drug is concentration-dependent, increasing from 78% at 0.5 mcg/mL to 19% at 50 mcg/mL.

Vutrisiran is metabolized by endo- and exonucleases to short nucleotide fragments of varying sizes within the liver. Approximately 19.4% of a dose is excreted as unchanged drug in urine following administration of the recommended dose of 25 mg. A median elimination half-life of 5.2 hours was reported following a single 25-mg dose of vutrisiran in healthy subjects.

No clinically important differences in vutrisiran pharmacokinetics were observed based on age, sex, race, mild or moderate renal impairment (estimated GFR >=30 to <90 mL/minute per 1.73 m2), or mild or moderate hepatic impairment. Vutrisiran pharmacokinetics have not been studied in patients with severe renal impairment, end-stage renal disease, severe hepatic impairment, or prior liver transplant.

USES: Vutrisiran is used to treat a certain type of heart failure or nerve problems due to a certain inherited condition (transthyretin-mediated amyloidosis). This condition causes a protein that your body normally makes (transthyretin-TTR), to change shape and build up in different parts of your body, which can affect the nerves, heart, and stomach/intestines. This medication works by decreasing the buildup of TTR in your body.

In people with heart failure, it may help lower the risk of death from heart disease, prevent the worsening of heart failure, and decrease the need to go to a hospital to treat heart failure.

Generic name: vutrisiran sodium
Pronunciation: (VUE-tri-SIR-an)
Drug class: Amyloidosis Agents - Transthyretin (TTR) Suppression
Therapeutic class: Endocrine

The following indications are listed for Amvuttra:

• Transthyretin Familial Amyloid Polyneuropathy
• Transthyretin-Related Amyloid Cardiomyopathy

Also known as: Cardiomyopathy Due To Attr, Polyneuropathy Due To Attr, Polyneuropathy Due To Transthyretin Amyloidosis, Transthyretin Amyloid Cardiomyopathy, Transthyretin Amyloid Polyneuropathy, Ttr Familial Amyloid Polyneuropathy.