ORENCIA

What it is

ORENCIA is abatacept, a fusion protein produced by recombinant DNA technology in Chinese hamster ovary cells. The lyophilised powder for intravenous infusion contains 250 mg abatacept per vial. The solution for subcutaneous administration is supplied as a pre-filled syringe or autoinjector containing 125 mg abatacept per 1 mL.

Approved indications

— Treatment of moderate to severe active rheumatoid arthritis in adult patients who have had an insufficient response or intolerance to other disease-modifying anti-rheumatic drugs, such as methotrexate or tumour necrosis factor blocking agents, in combination with methotrexate. — Treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated with methotrexate, in combination with methotrexate. — Reducing signs and symptoms in paediatric patients 6 years of age and older with moderately to severely active polyarticular juvenile idiopathic arthritis who have had an inadequate response to one or more disease-modifying anti-rheumatic drugs. — Treatment of active psoriatic arthritis in adults when the response to previous disease-modifying anti-rheumatic drug therapy has been inadequate.

Dosing overview

For adult rheumatoid arthritis and psoriatic arthritis, ORENCIA intravenous infusion is administered as a 30-minute infusion at doses based on body weight: less than 60 kg receives 500 mg, 60 to 100 kg receives 750 mg, and greater than 100 kg receives 1 gram. Following the initial infusion, further infusions are given at 2 and 4 weeks after the first infusion and every 4 weeks thereafter. For rheumatoid arthritis, ORENCIA subcutaneous injection is administered weekly at a dose of 125 mg regardless of weight. For psoriatic arthritis, ORENCIA subcutaneous injection is administered weekly at a dose of 125 mg without the need for an intravenous loading dose. For juvenile idiopathic arthritis in patients 6 to 17 years of age weighing less than 75 kg, the recommended dose is 10 mg/kg based on body weight at each administration. Paediatric patients weighing 75 kg or more follow the adult dosing regimen, not to exceed 1000 mg, administered as a 30-minute intravenous infusion with subsequent infusions at 2 and 4 weeks after the first infusion and every 4 weeks thereafter.

Key safety warnings

ORENCIA should not be administered to patients with severe infections such as sepsis, abscesses, tuberculosis, and opportunistic infections. Serious infections, including sepsis and pneumonia, have been reported in patients receiving ORENCIA, and some of these infections have been fatal. In placebo-controlled clinical trials, patients receiving concomitant intravenous ORENCIA and tumour necrosis factor blocking agent therapy experienced more infections (24%) and serious infections (2.2%) compared to patients treated with only tumour necrosis factor blocking agents (19% and 0.8%, respectively), and concurrent therapy with ORENCIA and a tumour necrosis factor blocking agent is not recommended. Anaphylaxis or anaphylactoid reactions can occur after the first infusion and can be life-threatening, and in postmarketing experience, a case of fatal anaphylaxis following the first infusion of ORENCIA has been reported. Cases of progressive multifocal leukoencephalopathy have been reported in patients receiving abatacept mostly in combination with other immunosuppressive medication. Progressive multifocal leukoencephalopathy can be fatal and should be considered in the differential diagnosis in immunosuppressed patients with new onset or worsening neurological, psychiatric and cognitive symptoms. If symptoms suggestive of progressive multifocal leukoencephalopathy occur during ORENCIA therapy, treatment should be discontinued and appropriate diagnostic measures initiated. Chronic obstructive pulmonary disease adult patients treated with ORENCIA developed adverse events more frequently than those treated with placebo, including chronic obstructive pulmonary disease exacerbations, cough, rhonchi, and dyspnoea. Use of ORENCIA in patients with rheumatoid arthritis and chronic obstructive pulmonary disease should be undertaken with caution and such patients should be monitored for worsening of their respiratory status.

Contraindications

ORENCIA should not be administered to patients with known hypersensitivity to ORENCIA or any of its components. ORENCIA should not be administered to patients with severe infections such as sepsis, abscesses, tuberculosis, and opportunistic infections.

PBS listing

The powder for intravenous infusion 250 mg is listed on the PBS with 4 items under streamlined and authority-required restrictions at an ex-manufacturer price of A$262.40. The injection 125 mg in 1 mL single-dose pre-filled syringe is listed with 3 items under authority-required and streamlined restrictions at an ex-manufacturer price of A$839.67. The injection 125 mg in 1 mL single-dose autoinjector is listed with 3 items under authority-required and streamlined restrictions at an ex-manufacturer price of A$839.67.

Regulatory history

ORENCIA abatacept 250 mg powder for intravenous infusion was first listed on the ARTG on 27 September 2007. The 125 mg single-dose syringe for subcutaneous injection was first listed on 4 January 2012, and the 125 mg single-dose autoinjector was first listed on 17 June 2015. In November 2015, the PBAC recommended listing of the 125 mg/mL injection autoinjector as a Section 85 Authority Required listing for rheumatoid arthritis. In November 2017, the PBAC recommended an amendment to allow abatacept to be used as a first-line biological disease-modifying anti-rheumatic drug for rheumatoid arthritis. An AusPAR was issued on 10 January 2018 for the indication of active psoriatic arthritis in adults with inadequate response to previous disease-modifying anti-rheumatic drug therapy.