Australian Public Assessment Report for Maraviroc
Total Page：16
File Type：pdf, Size：1020Kb
Australian Public Assessment Report for Maraviroc Proprietary Product Name: Celsentri Sponsor: ViiV Healthcare Pty Ltd May 2013 Therapeutic Goods Administration About the Therapeutic Goods Administration (TGA) • The Therapeutic Goods Administration (TGA) is part of the Australian Government Department of Health and Ageing, and is responsible for regulating medicines and medical devices. • The 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 <http://www.tga.gov.au>. 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. Copyright © Commonwealth of Australia 2013 This work is copyright. You may reproduce the whole or part of this work in unaltered form for your own personal use or, if you are part of an organisation, for internal use within your organisation, but only if you or your organisation do not use the reproduction for any commercial purpose and retain this copyright notice and all disclaimer notices as part of that reproduction. Apart from rights to use as permitted by the Copyright Act 1968 or allowed by this copyright notice, all other rights are reserved and you are not allowed to reproduce the whole or any part of this work in any way (electronic or otherwise) without first being given specific written permission from the Commonwealth to do so. Requests and inquiries concerning reproduction and rights are to be sent to the TGA Copyright Officer, Therapeutic Goods Administration, PO Box 100, Woden ACT 2606 or emailed to <[email protected]>. AusPAR Celsentri Maraviroc ViiV Healthcare Pty Ltd PM-2010-02896-3-2 Page 2 of 56 Date of finalisation: 12 May 2013 Therapeutic Goods Administration Contents I. Introduction to product submission ____________________________________ 4 Submission details ____________________________________________________________________ 4 Product background __________________________________________________________________ 4 Regulatory status _____________________________________________________________________ 5 Product Information__________________________________________________________________ 5 II. Quality findings ___________________________________________________________ 5 III. Nonclinical findings _____________________________________________________ 5 IV. Clinical findings __________________________________________________________ 5 Introduction ___________________________________________________________________________ 6 Pharmacokinetics ____________________________________________________________________ 11 Pharmacodynamics__________________________________________________________________ 12 Efficacy _______________________________________________________________________________ 12 Safety _________________________________________________________________________________ 19 List of questions _____________________________________________________________________ 20 First round clinical summary and conclusions ____________________________________ 21 Supplementary clinical evaluation report _________________________________________ 22 Second round recommendation regarding authorisation ________________________ 35 V. Pharmacovigilance findings ___________________________________________ 35 Risk management plan ______________________________________________________________ 35 VI. Overall conclusion and risk/benefit assessment _________________ 39 Quality ________________________________________________________________________________ 39 Nonclinical ___________________________________________________________________________ 39 Clinical ________________________________________________________________________________ 39 Risk management plan ______________________________________________________________ 46 Risk-benefit analysis ________________________________________________________________ 46 Outcome ______________________________________________________________________________ 54 Attachment 1. Product Information ___________________________________ 54 Attachment 2. Extract from the Clinical Evaluation Report ________ 55 AusPAR Celsentri Maraviroc ViiV Healthcare Pty Ltd PM-2010-02896-3-2 Page 3 of 56 Date of finalisation: 12 May 2013 Therapeutic Goods Administration I. Introduction to product submission Submission details Type of Submission: Major variation – extension of indications Decision: Approved Date of Decision: 22 August 2012 Active ingredient: Maraviroc Product Name: Celsentri Sponsor’s Name and Address: ViiV Healthcare Pty Ltd Level 4, 436 Johnston street, Abbotsford VIC 3067 Dose form: Tablet Strengths: 150 mg and 300 mg Containers: Bottle, blister pack Pack sizes: 180 tablets (bottle); 60 tablets (blister) Approved Therapeutic use: Celsentri, in combination with other antiretroviral medicinal products, is indicated for adult patients infected with only CCR5-tropic HIV-1. The use of other active agents with Celsentri is associated with a greater likelihood of treatment response. Route of administration: Oral Dosage (abbreviated): Adults: 150 mg, 300 mg or 600 mg twice daily depending on interactions with co-administered antiretroviral therapy and other medicinal products. ARTG Numbers: 137330, 137332, 137331, 137329 Product background An essential step in the human immunodeficiency virus (HIV) replication cycle is attachment to both the helper T cell (CD4+) receptor and one of the chemokine co-receptors (CC), either CCR5 or CXCR4.1 Maraviroc is a selective CCR5 co-receptor antagonist, active in vitro against a wide range of clinical isolates including those resistant to existing drug classes. 1 CCR5 and CXCR4 are also referred to as R5 and X4, respectively, in this report. AusPAR Celsentri Maraviroc ViiV Healthcare Pty Ltd PM-2010-02896-3-2 Page 4 of 56 Date of finalisation: 12 May 2013 Therapeutic Goods Administration Celsentri was first registered on the Australian Register of Therapeutic Goods (ARTG) in February 2008 for treatment experienced adult patients, as follows: Celsentri, in combination with other antiretroviral medicinal products, is indicated for treatment-experienced adult patients infected with only CCR5-tropic HIV-1. This indication is based on analyses of plasma HIV-1 RNA levels and CD4+ cell counts at 24 weeks in two double-blind, placebo-controlled trials in treatment-experienced patients with clinically advanced disease resistant to three or four classes of antiretrovirals. The use of other active agents with CELSENTRI is associated with a greater likelihood of treatment response. This AusPAR describes the application by ViiV Healthcare Pty Ltd (the sponsor) to extend the approved indications for Celsentri to include treatment naïve patients. The requested (amended) indications are: Celsentri, in combination with other antiretroviral medicinal product, is indicated for adult patients infected with CCR5-tropic HIV-1. The use of other active agents with CELSENTRI is associated with a greater likelihood of treatment response. Regulatory status Celsentri received initial ARTG Registration on 4 February 2008. At the time of the current application, a similar application and data package were submitted to Canada, the European Union (EU) and the United States (US). Canada and the US approved the indication for treatment naïve patients. Both have included in the Indication, a statement concerning the risk of development of viral resistance to lamivudine and emergence of CXCR4 tropic HIV-1 and instruction to use highly sensitive tropism testing prior to initiating therapy. The application was rejected in the EU. Product Information The approved product information (PI) current at the time this AusPAR was prepared can be found as Attachment 1. II. Quality findings There was no requirement for a quality evaluation in a submission of this type. III. Nonclinical findings There was no requirement for a nonclinical evaluation in a submission of this type. IV. Clinical findings A summary of the clinical findings is presented in this section. Further details of these clinical findings can be found in Attachment 2. AusPAR Celsentri Maraviroc ViiV Healthcare Pty Ltd PM-2010-02896-3-2 Page 5 of 56 Date of finalisation: 12 May 2013 Therapeutic Goods Administration Introduction Background and rationale The rationale