PROLIA

What it is

Prolia is the Amgen Inc. trademark for denosumab . Each 1 mL single-use pre-filled syringe contains 60 mg denosumab . Prolia is a sterile, preservative-free, clear, colourless to slightly yellow solution for injection . Denosumab is a fully human IgG2 monoclonal antibody with high affinity and specificity for RANK ligand (RANKL) .

Approved indications

— Treatment of osteoporosis in postmenopausal women, where Prolia significantly reduces the risk of vertebral, non-vertebral and hip fractures . — Treatment to increase bone mass in men with osteopaenia receiving androgen deprivation therapy for non-metastatic prostate cancer . — Treatment to increase bone mass in men with osteoporosis at increased risk of fracture . — Treatment to increase bone mass in women and men at increased risk of fracture due to long-term systemic glucocorticoid therapy .

Dosing overview

The recommended dose of Prolia is a single subcutaneous injection of 60 mg, once every 6 months . To reduce the risk of hypocalcaemia, patients must be adequately supplemented with calcium and vitamin D; in the major clinical trials, daily supplementation with 1,000 mg of calcium and at least 400 IU vitamin D was recommended .

Key safety warnings

Hypocalcaemia must be corrected prior to initiating therapy with Prolia. In the post-marketing setting, severe symptomatic hypocalcaemia (resulting in hospitalisation, life-threatening events and fatal cases) has been reported, particularly in patients with severe renal impairment, receiving dialysis or treatment with other calcium lowering drugs . Clinical monitoring of calcium levels is recommended before each dose . Patients receiving Prolia may develop skin infections (predominantly cellulitis) leading to hospitalisation. Patients should be advised to seek prompt medical attention if they develop signs or symptoms of cellulitis . Osteonecrosis of the jaw (ONJ) has been reported in patients treated with denosumab or bisphosphonates. Most cases have been in cancer patients; however some have occurred in patients with osteoporosis. ONJ has been reported rarely in clinical studies in patients receiving denosumab at a dose of 60 mg every 6 months for osteoporosis . It is important to evaluate patients for risk factors for ONJ before starting treatment. If risk factors are identified, a dental examination with appropriate preventive dentistry is recommended prior to treatment with Prolia. Good oral hygiene practices should be maintained during treatment with Prolia . Atypical femoral fractures have been reported in patients receiving Prolia. Atypical femoral fractures may occur with little or no trauma in the subtrochanteric and diaphyseal regions of the femur and may be bilateral . Multiple vertebral fractures (MVF) may occur following discontinuation of treatment with Prolia, particularly in patients with a history of vertebral fracture. New vertebral fractures occurred as early as 7 months after the last dose of Prolia .

Contraindications

Hypocalcaemia . Hypersensitivity to the active substance, to CHO-derived proteins or to any of the excipients . Pregnancy and in women trying to get pregnant .

PBS listing

Prolia was recommended by PBAC in November 2014 for the prevention of skeletal-related events in patients with bone metastases from solid tumours, and in July 2016 for osteoporosis with a change allowing initiation of treatment by nurse practitioners . Two ARTG registrations are held: a 60 mg/1 mL solution for injection pre-filled syringe, and a 60 mg/1 mL solution for injection pre-filled syringe with automatic needle guard, both first listed in June 2010 . Specific PBS item numbers, restriction types and ex-manufacturer prices are not provided in the available source documents.

Regulatory history

Prolia (denosumab) was first listed on the ARTG on 2010-06-07 and 2010-06-22 . The TGA approved Prolia on 2010-10-26 for the treatment of osteoporosis in postmenopausal women, noting its significant reduction in vertebral, non-vertebral and hip fractures . The application for the treatment of bone loss associated with hormone ablation in men with prostate cancer was rejected . PBAC recommended Prolia in November 2014 for prevention of skeletal-related events in patients with bone metastases from solid tumours . In July 2016, PBAC recommended a change to the PBS listing to allow initiation of treatment of osteoporosis by nurse practitioners . In August 2017, PBAC noted that new evidence did not raise additional concerns about long-term safety but noted that ceasing denosumab therapy can lead to early onset of loss of clinical benefit .