Vilsin-60

Indications & Use

Vilsin60 is a gene therapy based on adenovirus vectors, used to treat adults with severe hemophilia A (congenital factor VIII deficiency, factor VIII activity < 1 IU/dL) who have not been tested for pre-existing adenovirus serotype 5 antibodies and have been approved by the FDA.

That is: an AAV-based gene therapy for adult patients with severe hemophilia A (congenital factor VIII deficiency, FVIII activity < 1 IU/dL). Pre-treatment testing for existing adenovirus serotype 5 (AAV5) antibodies is required; the product has been approved by the FDA.

Mechanism of Action

Gene therapy based on adenovirus vectors (gene therapy based on adenovirus vectors).

Prerequisites for use

• Pre-treatment testing for existing adenovirus serotype 5 (AAV5) antibodies
• Testing for the presence of factor VIII inhibitors
• Liver function assessment

Dosage & Administration

For one-time single-dose intravenous injection only (for one-time single dose intravenous injection only).

Recommended dose

6 × 10¹³ vector genomes (vg) per kg of body weight.

Infusion rate

Start at 1 mL/min; if well tolerated, increase by 1 mL/min every 30 minutes, up to a maximum of 4 mL/min.

Specifications & Presentation

Suspension for intravenous infusion.

Nominal concentration: 2 × 10¹³ vg of valoctogene roxaparvovec rvox per mL; extractable volume per vial not less than 8 mL (i.e., 16 × 10¹³ vg). Each carton contains a single-dose vial.

Appearance: sterile, preservative-free, clear colorless to pale yellow suspension.

Storage & Preparation

Storage

≤ -60 °C (-76 °F) frozen transport; store upright in the carton, protected from light.

During thawing & preparation

• Thaw at room temperature (not exceeding 25 °C / 77 °F)
• After thawing, may be kept at room temperature for up to 10 hours, including preparation and infusion time
• If storage is needed, intact un-punctured vials may be refrigerated upright, protected from light (e.g., in the original carton) at 2–8 °C for up to 3 days
• Must not be exposed to UV disinfection lamps
• Do not refreeze after thawing

Spill handling

Spilled product should be treated with a virucidal agent with proven activity against non-enveloped viruses and absorbed with absorbent material. Dispose of unused product and all disposable materials that may have contacted the product according to local pharmaceutical waste guidelines.

Contraindications

• Active infection, including acute infection or uncontrolled chronic infection
• Known significant hepatic fibrosis (stage 3 or 4) or cirrhosis
• Known allergy to mannitol

Warnings & Precautions

Adverse Reactions

Most common adverse reactions (incidence ≥ 5%)

Nausea, fatigue, headache, infusion-related reactions, vomiting, abdominal pain.

Most common laboratory abnormalities (incidence ≥ 10%)

ALT, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatine phosphokinase (CPK), factor VIII activity levels, gamma-glutamyl transferase (GGT), bilirubin > ULN.

Use in Special Populations

• Within 6 months after administration, males must not donate semen, and male patients and their female partners must prevent or postpone pregnancy
• Safety and efficacy data for Vilsin-60 in HIV-infected patients are limited
• Safety and efficacy in patients with pre-existing or active factor VIII inhibitors have not been established