AMVUTTRA

What it is

Amvuttra contains vutrisiran sodium equivalent to 25 mg vutrisiran in 0.5 mL solution for injection. It is a solution for injection presented as a clear, colourless to yellow sterile solution practically free from visible particles. Amvuttra contains vutrisiran, a chemically stabilised double-stranded small interfering ribonucleic acid (siRNA) that specifically targets variant and wild-type transthyretin (TTR) messenger RNA, causing the catalytic degradation of TTR mRNA in the liver and resulting in the reduction of variant and wild-type serum TTR protein levels. This medicinal product is subject to additional monitoring in Australia to allow quick identification of new safety information.

Approved indications

— Treatment of hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) in adult patients with stage 1 or stage 2 polyneuropathy.

Dosing overview

The recommended dose of Amvuttra is 25 mg administered via subcutaneous injection once every 3 months. Therapy should be initiated under the supervision of a physician knowledgeable in the management of amyloidosis, and treatment should be started as early as possible in the disease course to prevent the accumulation of disability. Vitamin A supplementation at approximately, but not exceeding, 2500 IU to 3000 IU vitamin A per day is advised for patients treated with Amvuttra. Amvuttra should be administered by a healthcare professional.

Key safety warnings

By reducing serum transthyretin (TTR) protein, Amvuttra treatment leads to a decrease in serum vitamin A (retinol) levels. Serum vitamin A levels below the lower limit of normal should be corrected and any ocular symptoms or signs due to vitamin A deficiency should be evaluated prior to initiation of treatment with Amvuttra. Patients receiving Amvuttra should take oral supplementation of approximately, but not exceeding, 2500 IU to 3000 IU vitamin A per day to reduce the potential risk of ocular symptoms due to vitamin A deficiency. Ophthalmological assessment is recommended if patients develop ocular symptoms suggestive of vitamin A deficiency, including reduced night vision or night blindness, persistent dry eyes, eye inflammation, corneal inflammation or ulceration, corneal thickening or corneal perforation. During the first 60 days of pregnancy, both too high or too low vitamin A levels may be associated with an increased risk of fetal malformation. Therefore, pregnancy should be excluded before initiating Amvuttra and women of childbearing potential should practise effective contraception. If a woman intends to become pregnant, Amvuttra and vitamin A supplementation should be discontinued and serum vitamin A levels should be monitored and have returned to normal before conception is attempted. Serum vitamin A levels may remain reduced for more than 12 months after the last dose of Amvuttra. The most frequently occurring adverse reactions reported in Amvuttra-treated patients during the 18-month treatment period of the clinical study HELIOS-A were pain in extremity (15%) and arthralgia (11%). Other adverse reactions included dyspnoea (common) and injection site reaction (common), with reported symptoms including bruising, erythema, pain, pruritus, and warmth. Injection site reactions were mild, transient, and did not lead to treatment discontinuation.

Contraindications

Severe hypersensitivity (e.g., anaphylaxis) to the active substance or to any of the excipients.

PBS listing

In November 2024, the PBAC recommended Amvuttra for hereditary transthyretin-mediated (hATTR) amyloidosis in adult patients with stage 1 or stage 2 polyneuropathy as a Section 100 (Highly Specialised Drugs Program — Public and Private Hospitals) Authority Required listing.

Regulatory history

Amvuttra (vutrisiran 25 mg / 0.5 mL solution for injection pre-filled syringe) was first listed on the ARTG on 21 June 2024. The TGA approved Amvuttra on 18 June 2024 for the treatment of hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) in adult patients with stage 1 or stage 2 polyneuropathy. The TGA's quality evaluation found the manufacturing process, analytical methods, and product specifications acceptable. Nonclinical studies raised no objections, supporting the drug's mechanism of action in reducing TTR protein levels and identifying reversible, non-adverse target organ effects in the liver, kidneys, and injection site. In November 2024, the PBAC recommended Amvuttra for Authority Required listing.