We will have limited operations from 15:00 Tuesday 24 December 2024 (AEDT) until Thursday 2 January 2025. Find out how to contact us during the holiday period.
Amvuttra (vutrisiran)
Australian Prescription Medicine Decision Summary
Sponsor
ARTGs
Device/Product name
Amvuttra
Active Ingredient
Vutrisiran
Date of decision
Published
Submission type
Type A (New chemical entity)
ATC codes
N07XX18 (other nervous system drugs)
Decision
Approved
What was the decision based on
The decision to approve Amvuttra was based on quality (chemistry and manufacturing), nonclinical (pharmacology and toxicology studies conducted in animal models), clinical (pharmacology, safety and efficacy trials in humans) and risk management plan data submitted to the TGA by the sponsor.
Key trials in humans that supported the proposed indication included a Phase 1 single-dose study in healthy volunteers and a pivotal Phase 3 study in hATTR amyloidosis patients with polyneuropathy.
Key trials in humans that supported the proposed indication included a Phase 1 single-dose study in healthy volunteers and a pivotal Phase 3 study in hATTR amyloidosis patients with polyneuropathy.
What steps were involved in the decision process
The active ingredient with its proposed indication was given orphan drug designation and was evaluated under the Comparable Overseas Regulator B (COR-B) report-based process.
| Description | Date |
|---|---|
| Designation (Orphan) | 28 August 2023 |
| Submission dossier accepted and first round evaluation commenced | 31 October 2023 |
| First round evaluation completed | 29 February 2024 |
| Sponsor provides responses on questions raised in first round evaluation | 28 March 2024 |
| Second round evaluation completed | 22 April 2024 |
| Delegate’s Overall benefit-risk assessment | 15 May 2024 |
| Registration decision (Outcome) | 18 June 2024 |
| Administrative activities and registration in the ARTG completed | 21 June 2024 |
| Number of working days from submission dossier acceptance to registration decision* | 161 |
*The COR-B process has a 175 working day evaluation and decision timeframe.
Date of entry onto ARTG
Black triangle scheme
Amvuttra (vutrisiran) is to be included in the Black Triangle Scheme. The PI and CMI
for Amvuttra must include the black triangle symbol and mandatory accompanying text
for five years, which starts from the date of first supply of the product.
for Amvuttra must include the black triangle symbol and mandatory accompanying text
for five years, which starts from the date of first supply of the product.
Dose forms
Amvuttra is a clear, colourless to yellow sterile solution practically free from visible particles.
Strength
Each pre-filled syringe contains vutrisiran sodium equivalent to 25 mg vutrisiran in 0.5 mL solution.
Other ingredients
- Monobasic sodium phosphate dihydrate
- Dibasic sodium phosphate dihydrate
- Sodium chloride
- Water for injections
- Sodium hydroxide (for pH adjustment)
- Phosphoric acid (for pH adjustment)
Containers
Pre-filled syringe (Type I glass with a bromobutyl rubber, fluoropolymer coated, plunger stopper) with stainless steel 29-gauge needle with a needle shield.
Pack sizes
One single-use pre-filled syringe per pack.
Routes of administration
Amvuttra is administered via subcutaneous injection.
Dosage
The recommended dose of Amvuttra is 25 mg administered via subcutaneous injection once every 3 months.
Pregnancy category
D
Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects.
Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects.
What was approved
Amvuttra was approved for the treatment of hereditary transthyretin-mediated amyloidosis in adult patients with stage 1 or stage 2 polyneuropathy.
What is this medicine and how does it work
Amvuttra is used to treat polyneuropathy (when multiple peripheral nerves are damaged) caused by hereditary transthyretin-mediated (hATTR) amyloidosis. In hATTR, abnormal proteins called amyloids accumulate around the nerves. Amvuttra contains vutrisiran, a small interfering ribonucleic acid (siRNA) that is delivered to liver cells and specifically targets transthyretin (TTR). Through a natural process called RNA interference (RNAi), vutrisiran causes the degradation of TTR mRNA in the liver, resulting in the reduction of TTR protein levels.
TTR transports vitamin A (retinol) and a hormone called thyroxine throughout the body. To perform this transport function, TTR units must form a tetramer (a protein complex made up of four TTR subunits). Patients with hATTR possess TTR gene variants that prevent tetramer formation and form fibril clumps instead which form amyloid. These amyloid deposits cause the symptoms of hATTR by accumulating in certain tissues. Amvuttra alleviates these symptoms by reducing TTR synthesis which leads to reduced levels of amyloid deposits.
TTR transports vitamin A (retinol) and a hormone called thyroxine throughout the body. To perform this transport function, TTR units must form a tetramer (a protein complex made up of four TTR subunits). Patients with hATTR possess TTR gene variants that prevent tetramer formation and form fibril clumps instead which form amyloid. These amyloid deposits cause the symptoms of hATTR by accumulating in certain tissues. Amvuttra alleviates these symptoms by reducing TTR synthesis which leads to reduced levels of amyloid deposits.
What post-market commitments will the sponsor undertake
The Amvuttra Risk Management Plan (RMP) as agreed with the TGA will be implemented in Australia. An obligatory component of RMPs is routine pharmacovigilance, which includes the submission of periodic safety update reports.
More information
The latest Product Information (PI) and Consumer Medicine Information (CMI) can be found by searching the Australian Register of Therapeutic Goods (ARTG).
Australian Public Assessment Reports (AusPARs) can be found by searching our AusPAR dataset.
The latest news and updates regarding therapeutic goods regulation can be found on our news page.