Australian Public Assessment Report for Abatacept (Rch)
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Australian Public Assessment Report for Abatacept (rch) Proprietary Product Name: Orencia Sponsor: Bristol-Myers Squibb Australia Pty Ltd June 2011 About the Therapeutic Goods Administration (TGA) · The TGA is a division of the Australian Government Department of Health and Ageing, and is responsible for regulating medicines and medical devices. · TGA administers the Therapeutic Goods Act 1989 (the Act), applying a risk management approach designed to ensure therapeutic goods supplied in Australia meet acceptable standards of quality, safety and efficacy (performance), when necessary. · The work of the TGA is based on applying scientific and clinical expertise to decision- making, to ensure that the benefits to consumers outweigh any risks associated with the use of medicines and medical devices. · The TGA relies on the public, healthcare professionals and industry to report problems with medicines or medical devices. TGA investigates reports received by it to determine any necessary regulatory action. · To report a problem with a medicine or medical device, please see the information on the TGA website. About AusPARs · An Australian Public Assessment Record (AusPAR) provides information about the evaluation of a prescription medicine and the considerations that led the TGA to approve or not approve a prescription medicine submission. · AusPARs are prepared and published by the TGA. · An AusPAR is prepared for submissions that relate to new chemical entities, generic medicines, major variations, and extensions of indications. · An AusPAR is a static document, in that it will provide information that relates to a submission at a particular point in time. · A new AusPAR will be developed to reflect changes to indications and/or major variations to a prescription medicine subject to evaluation by the TGA. AusPAR Orencia EOI Abatacept (rch) Bristol-Myers Squibb Australia Pty Ltd PM-2010-00413-3-3 Page 2 of 135 Final 15 June 2011 Contents I. Introduction to Product Submission ____________________________________ 4 Submission Details _________________________________________________________________________ 4 Product Background _______________________________________________________________________ 5 Regulatory Status __________________________________________________________________________ 6 Product Information _______________________________________________________________________ 6 II. Quality Findings ____________________________________________________________ 6 Drug Product _______________________________________________________________________________ 6 Quality Summary and Conclusions _______________________________________________________ 6 III. Nonclinical Findings ______________________________________________________ 6 Nonclinical Summary and Conclusions __________________________________________________ 6 IV. Clinical Findings ___________________________________________________________ 6 Introduction ________________________________________________________________________________ 6 Pharmacodynamics ________________________________________________________________________ 8 Pharmacokinetics ________________________________________________________________________ 12 Efficacy ____________________________________________________________________________________ 13 Safety ______________________________________________________________________________________ 49 Clinical Summary and Conclusions _____________________________________________________ 84 V. Pharmacovigilance Findings ___________________________________________ 86 Risk Management Plan __________________________________________________________________ 86 VI. Overall Conclusion and Risk/Benefit Assessment _________________ 90 Quality _____________________________________________________________________________________ 90 Nonclinical ________________________________________________________________________________ 90 Clinical ____________________________________________________________________________________ 90 Risk Management Plan __________________________________________________________________ 99 Risk-Benefit Analysis ___________________________________________________________________ 100 Outcome __________________________________________________________________________________ 104 Attachment 1. Product Information ___________________________________105 AusPAR Orencia EOI Abatacept (rch) Bristol-Myers Squibb Australia Pty Ltd PM-2010-00413-3-3 Page 3 of 135 Final 15 June 2011 I. Introduction to Product Submission Submission Details Type of Submission Extension of Indications Decision: Approved Date of Decision: 23 March 2011 Active ingredient(s): Abatacept (rch) Product Name(s): Orencia Sponsor’s Name and Address: Bristol-Myers Squibb Australia Pty Ltd 556 Princes Highway Noble Park Vic 3174 Dose form(s): Powder for IV infusion Strength(s): 250 mg Container(s): Single-use vial with a silicone-free disposable syringe Pack size(s): Individually packaged Approved Therapeutic use: Orencia in combination with methotrexate is indicated for the 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 (DMARDs), such as methotrexate or tumour necrosis factor (TNF) blocking agents. A reduction in the progression of joint damage and improvement in physical function have been demonstrated during combination treatment with Orencia and methotrexate. Orencia in combination with methotrexate is also indicated in the treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated with methotrexate. Orencia is indicated for reducing signs and symptoms in paediatric patients 6 years of age and older with moderately to severely active polyarticular juvenile idiopathic arthritis who had an inadequate response to one or more disease-modifying anti-rheumatic drugs (DMARDS). Orencia may be used as monotherapy or concomitantly with methotrexate (MTX). Orencia should not be administered concurrently with other biological DMARDs (eg, TNF inhibitors, rituximab, or anakinra). Route(s) of administration: IV infusion Dosage: Following the initial administration, Orencia should be given at 2 and 4 weeks after the first infusion, then every 4 weeks thereafter, 500 mg, 750 mg or 1 g, depending on body weight. ARTG Number (s) 130100 AusPAR Orencia EOI Abatacept (rch) Bristol-Myers Squibb Australia Pty Ltd PM-2010-00413-3-3 Page 4 of 135 Final 15 June 2011 Product Background This AusPAR describes the evaluation of a submission from the sponsor, Bristol-Myers Squibb Australia Pty Ltd for an extension of indications for abatacept (Orencia). An extension of indications for Orencia to allow treatment of paediatric patients with moderately to severely active polyarticular juvenile idiopathic arthritis was recently approved by the TGA.1 The submission also proposes the updating of the product information with long-term efficacy and safety data for the use of Orencia in rheumatoid arthritis. Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by progressive inflammatory synovitis manifested by polyarticular joint swelling. Activation of T-lymphocytes is an important mediator in the pathogenesis of RA, particularly early in the disease process, because it results in amplification of the pro- inflammatory disease cascade. Abatacept is a selective co-stimulation modulator which inhibits T-cell activation by binding to CD80 and CD86, thereby blocking a crucial interaction with CD 28. The sponsor submitted that consistent with contemporary practice, early treatment of RA (particularly in those with poor prognostic factors such as the presence of autoantibodies and early radiographic erosion) is considered to offer the best outcomes. In addition, combination therapy involving biological and conventional disease modifying anti- rheumatic drug (DMARD) treatment is considered to offer the best opportunity to achieve favourable outcomes in adult patients with early aggressive RA. The extended indication proposed by the sponsor is: Orencia in combination with methotrexate is also indicated in the treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated with methotrexate. This paragraph is to be an additional insert between the first and second paragraphs of the current approved indication for Orencia which are as follows: Orencia in combination with methotrexate is indicated for the 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 (DMARDs), such as methotrexate or tumour necrosis factor (TNF) blocking agents. A reduction in the progression of joint damage and improvement in physical function have been demonstrated during combination treatment with Orencia and methotrexate. Orencia is indicated for reducing the 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 (DMARDs). Orencia may be used as monotherapy or concomitantly with methotrexate (MTX). Orencia should not be administered concurrently with other biological DMARDs (e.g. TNF inhibitors, rituximab or anakinra). The route of administration is per intravenous (IV) infusion over a 30 minute period. A weight tiered dosing of