SYLVANT

What it is

SYLVANT is a chimeric (human murine) immunoglobulin G1k (IgG1k) monoclonal antibody against human Interleukin-6 (IL-6) . SYLVANT is supplied as siltuximab 100 mg or 400 mg powder for injection vials . SYLVANT is supplied as a single-use vial containing a lyophilised cake of white powder for reconstitution .

Approved indications

— Treatment of patients with multicentric Castleman's disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative .

Dosing overview

The recommended dose is 11 mg/kg siltuximab given over 1 hour as an intravenous infusion administered every 3 weeks until treatment failure . Haematology laboratory tests should be performed prior to each dose of SYLVANT therapy for the first 12 months and every 3 dosing cycles thereafter .

Key safety warnings

Infections, including localised infections, should be treated prior to administration of SYLVANT. Serious infections including pneumonia and sepsis were observed during clinical studies . SYLVANT may mask signs and symptoms of acute inflammation including suppression of fever and of acute phase reactants such as C-reactive protein (CRP). Therefore, prescribers should diligently monitor patients receiving treatment in order to detect serious infections . Live, attenuated vaccines should not be given concurrently or within 4 weeks before initiating SYLVANT, because clinical safety has not been established and because IL-6 inhibition may interfere with the normal immune response to new antigens . Elevations in triglycerides and cholesterol (lipid parameters) were observed in patients treated with SYLVANT. Patients should be managed according to current clinical guidelines for management of hyperlipidaemia . Gastrointestinal (GI) perforation has been reported in siltuximab clinical trials although not in MCD trials. Use with caution in patients who may be at increased risk for GI perforation .

Contraindications

Severe hypersensitivity to the active substance or to any of the excipients .

PBS listing

SYLVANT 100 mg powder for injection is listed on the PBS with 2 items under authority required restriction, at an ex-manufacturer price of A$779.28. SYLVANT 400 mg powder for injection is listed on the PBS with 2 items under authority required restriction, at an ex-manufacturer price of A$3117.10 .

Regulatory history

SYLVANT siltuximab 100 mg and 400 mg powder for injection vials were first listed on the Australian Register of Therapeutic Goods on 31 August 2015 . The PBAC did not recommend SYLVANT for idiopathic multicentric Castleman's disease (IMCD) in July 2021, but recommended it in November 2021 .