SOMAVERT

What it is

SOMAVERT contains pegvisomant (rbe) . It is a powder for injection supplied as a sterile, white to slightly off-white lyophilised powder intended for subcutaneous injection after reconstitution with sterile Water for Injections . SOMAVERT is available in single-dose sterile vials containing 10, 15, or 20 mg of pegvisomant protein . Pegvisomant is an analogue of human growth hormone that has been structurally altered to act as a GH receptor antagonist . Pegvisomant binds to growth hormone receptors on cell surfaces, where it blocks the binding of endogenous growth hormone, and thus interferes with intracellular growth hormone signal transduction . Inhibition of growth hormone action with pegvisomant leads to decreased serum concentrations of insulin-like growth factor-I (IGF-I), as well as other growth hormone-responsive serum proteins .

Approved indications

— Treatment of acromegaly in patients who have had inadequate response to surgery and/or radiation and/or other medical therapies or for whom these therapies are not appropriate .

Dosing overview

A loading dose of 80 mg of SOMAVERT should be administered subcutaneously under medical supervision . Thereafter, the patient should begin daily subcutaneous injections of 10 mg of SOMAVERT . Serum IGF-I levels should be obtained every 4 to 6 weeks and appropriate dose adjustments made in increments of 5 mg/day in order to maintain the serum IGF-I level within the age-adjusted normal range and alleviate the signs and symptoms of acromegaly . The maximum daily maintenance dose should not exceed 30 mg . During treatment with SOMAVERT, patients on anti-diabetic therapy may need reduced doses of insulin or oral hypoglycaemic agents because SOMAVERT increases insulin sensitivity and glucose tolerance . Heavier individuals tend to have a higher total body clearance of pegvisomant than lighter individuals, and may thus require greater doses of pegvisomant .

Key safety warnings

Growth hormone-secreting pituitary tumours may sometimes expand, causing serious complications such as visual field defects, and it is essential that all patients be carefully monitored . Growth hormone opposes the effects of insulin on carbohydrate metabolism by decreasing insulin sensitivity and patients with acromegaly therefore have significant insulin resistance; thus, glucose tolerance may increase in some patients treated with SOMAVERT . SOMAVERT is a potent antagonist of growth hormone action, and a state of functional growth hormone deficiency may result from administration of SOMAVERT, despite the presence of elevated serum GH levels, if serum IGF-I levels drop below the age-adjusted normal range . Serum IGF-I levels should therefore be monitored and maintained within the age-adjusted normal range by adjustment of the dose of SOMAVERT . Elevations of serum concentrations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) greater than 10 times the upper limit of normal were reported in two patients (0.8%) treated with SOMAVERT during the clinical studies . Pegvisomant should not be initiated or continued if signs of liver disease are present, pending a comprehensive hepatic evaluation .

Contraindications

SOMAVERT is contraindicated in patients with a history of hypersensitivity to pegvisomant or any of the excipients .

PBS listing

SOMAVERT is listed on the PBS in four formulations: injection sets containing powder for injection 10 mg (30 vials), 15 mg (30 vials), 20 mg (1 vial), and 20 mg (30 vials), each with 30 diluent syringes in the relevant pack size. All items require authority approval, with ex-manufacturer prices of A$3969.64 per 30-vial pack and A$132.33 per single-vial pack .

Regulatory history

SOMAVERT was first approved on 9 December 2005 . ARTG registration records show three variants listed on 31 May 2017: SOMAVERT pegvisomant 10 mg, 15 mg, and 20 mg powder for injection vials with diluent in pre-filled syringes . The Pharmaceutical Benefits Scheme Advisory Committee recommended listing in November 2016 under the Highly Specialised Drugs Program with authority required restriction for acromegaly in patients with inadequate response to surgery and/or radiation and/or other medical therapies. In March 2019, PBAC recommended a change to the definition of failure to achieve biochemical control in the initial PBS restriction .