DUPIXENT

What it is

Dupixent contains dupilumab, a fully human monoclonal antibody produced by recombinant DNA technology in Chinese Hamster Ovary cell suspension culture. Dupixent is a recombinant human IgG4 monoclonal antibody that inhibits interleukin-4 and interleukin-13 signalling by specifically binding to the IL-4Rα subunit shared by the IL-4 and IL-13 receptor complexes. Dupixent is a sterile, preservative-free, clear to slightly opalescent, colourless to pale yellow solution for subcutaneous injection, which is free from visible particulates, pH 5.9.

Approved indications —

Moderate to severe atopic dermatitis in patients aged 12 years and older who are candidates for chronic systemic therapy. — Severe atopic dermatitis in patients aged 6 months to 11 years old who are candidates for chronic systemic therapy. — Moderate-to-severe prurigo nodularis in adults who are candidates for systemic therapy. — Add-on maintenance treatment in patients aged 6 years and older with moderate to severe asthma with type 2 inflammation (elevated eosinophils or elevated fractional exhaled nitric oxide [FeNO]) that is inadequately controlled despite therapy with other medicinal products for maintenance treatment. — Add-on maintenance treatment in adult patients with inadequately controlled chronic rhinosinusitis with nasal polyposis. — Add-on maintenance treatment in adults for uncontrolled chronic obstructive pulmonary disease characterised by raised blood eosinophils on a stable combination of an inhaled corticosteroid, a long-acting beta2-agonist, and a long-acting muscarinic antagonist, or on a combination of a long-acting beta2-agonist and a long-acting muscarinic antagonist if inhaled corticosteroid is not appropriate.

Dosing overview

For children and adolescents 6 to 17 years of age with atopic dermatitis, dosing is weight-based, ranging from 200 mg to 600 mg initial doses followed by maintenance doses every 2 to 4 weeks. For children 6 months to 5 years of age with atopic dermatitis, an initial loading dose is not recommended, with maintenance doses of 200 mg or 300 mg every 4 weeks based on body weight.

Key safety warnings

Hypersensitivity reactions, including anaphylaxis, serum sickness or serum sickness-like reactions and angioedema, have been reported. Anaphylactic reactions and angioedema have occurred from minutes to up to seven days after the dupilumab injection. Conjunctivitis and keratitis have been reported with Dupixent, predominantly in atopic dermatitis patients. Some patients reported visual disturbances such as blurred vision associated with conjunctivitis or keratitis. Patients with known helminth infections were excluded from participation in clinical studies. It is unknown if Dupixent will influence the immune response against helminth infections. Treat patients with pre-existing helminth infections before initiating Dupixent. If patients become infected while receiving treatment with Dupixent and do not respond to anti-helminth treatment, discontinue treatment with Dupixent until infection resolves. Patients being treated for asthma may present with serious systemic eosinophilia sometimes presenting with clinical features of eosinophilic pneumonia or vasculitis consistent with eosinophilic granulomatosis with polyangiitis. These events usually, but not always, may be associated with the reduction of oral corticosteroid therapy. Physicians should be alert to vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients with eosinophilia. Arthralgia has been reported with the use of Dupixent with some patients reporting gait disturbances or decreased mobility associated with joint symptoms; some cases resulted in hospitalisation. In postmarketing reports, onset of arthralgia was variable, ranging from days to months after the first dose of Dupixent. Some patients' symptoms resolved while continuing treatment with Dupixent and other patients recovered or were recovering following discontinuation of Dupixent. Advise patients to report new onset or worsening joint symptoms to their healthcare provider.

Contraindications

Dupixent is contraindicated in patients who have known hypersensitivity to dupilumab or any of its excipients.

PBS listing

Dupixent is available on the PBS as 200 mg and 300 mg formulations in single-dose pre-filled syringes and pre-filled pens. Multiple PBS items are listed for each strength and formulation with authority-required restriction. The ex-manufacturer price is A$1609.86 per unit across all strengths and formulations.

Regulatory history

Dupixent 300 mg pre-filled syringe with needle shield was first listed on the ARTG on 24 January 2018. The 200 mg pre-filled syringe with needle shield was first listed on 28 May 2019, and both the 300 mg and 200 mg pre-filled pens were first listed on 3 June 2022. In November 2017, the PBAC did not recommend Dupixent for severe atopic dermatitis due to uncertain cost-effectiveness and clinical benefit. However, in March 2020, the PBAC recommended listing for atopic dermatitis in patients aged 12 years and older with inadequate response to topical therapies. In November 2020, the PBAC recommended listing for asthma. In March 2022, the PBAC recommended listing for severe atopic dermatitis in patients aged 6 to 11 years. An AusPAR was issued on 23 June 2022 for approval of Dupixent's extension of indications to include paediatric patients aged 6 to 11 years with moderate to severe asthma with type 2 inflammation.