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Australian Public Assessment for Polatuzumab Vedotin Australian Public Assessment Report for Polatuzumab vedotin Proprietary Product Name: Polivy Sponsor: Roche Products Pty Ltd December 2019 Therapeutic Goods Administration About the Therapeutic Goods Administration (TGA) • The Therapeutic Goods Administration (TGA) is part of the Australian Government Department of Health 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 <https://www.tga.gov.au>. About AusPARs • An Australian Public Assessment Report (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; it provides 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 2019 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 for Polivy (polatuzumab vedotin) Roche Products Pty Limited PM-2019-00471-1-6 Page 2 of 20 Final 3 December 2019 Therapeutic Goods Administration Contents Common abbreviations _____________________________________________________ 4 I. Introduction to product submission ____________________________________ 6 Submission details ____________________________________________________________________ 6 Product background __________________________________________________________________ 6 Regulatory status _____________________________________________________________________ 7 Product Information__________________________________________________________________ 8 II. Registration time line ____________________________________________________ 8 III. Submission overview and risk/benefit assessment ________________ 8 Quality _________________________________________________________________________________ 8 Nonclinical ____________________________________________________________________________ 9 Clinical ________________________________________________________________________________ 10 Risk management plan ______________________________________________________________ 13 Risk-benefit analysis ________________________________________________________________ 15 Outcome ______________________________________________________________________________ 18 Attachment 1. Product Information _____________________________________ 19 AusPAR for Polivy (polatuzumab vedotin) Roche Products Pty Limited PM-2019-00471-1-6 Page 3 of 20 Final 3 December 2019 Therapeutic Goods Administration Common abbreviations Abbreviation Meaning ACM Advisory Committee on Medicines ADA Anti-drug antibody ADC Antibody-drug conjugate AE Adverse event ARTG Australian Register of Therapeutic Goods ASCT Autologous stem cell transplantation AST Aspartate aminotransferase AUC Area under the curve BG Bendamustine and obinutuzumab BR Bendamustine plus rituximab CI Confidence interval CLL Chronic lymphocytic leukaemia CMI Consumer Medicines Information CR Complete response CYP Cytochrome P40 (enzyme) DLBCL Diffuse large B-cell lymphoma EMA European Medicines Agency (EU) EU European Union FDA Food and Drug Administration (USA) GCP Good Clinical Practice HR Hazard ratio HSCT Haemopoietic stem cell transplantation IgG1 Immunoglobulin G1 IV Intravenous MDS Myelodysplastic syndrome MMAE Monomethyl auristatin E AusPAR for Polivy (polatuzumab vedotin) Roche Products Pty Limited PM-2019-00471-1-6 Page 4 of 20 Final 3 December 2019 Therapeutic Goods Administration Abbreviation Meaning MRI Magnetic resonance imaging OS Overall survival PFS Progression free survival PI Product Information PK Pharmacokinetic(s) PR Partial response R-CHOP Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone RMP Risk management plan SCT Stem cell transplant TGA Therapeutic Goods Administration USA United States of America AusPAR for Polivy (polatuzumab vedotin) Roche Products Pty Limited PM-2019-00471-1-6 Page 5 of 20 Final 3 December 2019 Therapeutic Goods Administration I. Introduction to product submission Submission details Type of submission: New biological entity Decision: Approved 18 October 2019 Date of decision: 21 October 2019 Date of entry onto ARTG: 314866 ARTG number: Yes. This product will remain in the scheme for 5 years, starting ‚Black Triangle Scheme on the date the product is first supplied in Australia Active ingredient: Polatuzumab vedotin Product name: Polivy Sponsor’s name and address: Roche Products Pty Limited 30-34 Hickson Road, Sydney NSW 2000 Dose form: Powder for injection Strength: 140 mg/mL Container: Vial Pack size: 1 Approved therapeutic use: Polivy in combination with bendamustine and rituximab is indicated for the treatment of previously treated adult patients with diffuse large B-cell lymphoma who are not candidates for hematopoietic stem cell transplant. Route of administration: Intravenous infusion (IV) The recommended dose of Polivy is 1.8 mg/kg given as an Dosage: intravenous infusion every 21 days in combination with bendamustine and rituximab for 6 cycles. For further information refer to the Product Information (PI). Product background This AusPAR describes the application by the sponsor, Roche Products Pty Ltd, to register the new biological entity polatuzumab vedotin as Polivy for the following indications: Polivy in combination with bendamustine and rituximab is indicated for the treatment of previously treated adult patients with diffuse large B-cell lymphoma who are not candidates for hematopoietic stem cell transplant. AusPAR for Polivy (polatuzumab vedotin) Roche Products Pty Limited PM-2019-00471-1-6 Page 6 of 20 Final 3 December 2019 Therapeutic Goods Administration Polivy is proposed to be used in combination with bendamustine and rituximab at a proposed dose of 1.8 mg/kg administered as an intravenous (IV) infusion (over 90 minutes (initial dose) or 30 minutes (subsequent doses)) every 21 days in combination with bendamustine and rituximab for 6 cycles (recommended duration of treatment). Polatuzumab vedotin consist of a CD79b-targeted antibody-drug conjugate that preferentially delivers a cytotoxic agent, an anti-mitotic agent (monomethyl auristatin E, (MMAE)), to B-cells, which results in the killing of malignant B-cells. Hence, it is intended to allow target specific cytotoxic treatment of malignant B-cells in diffuse large B-cell lymphoma (DLBCL). DLBCL is a usually treated initially with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP), which is curative in approximately 60% of patients. In those who are refractory to first-line therapy, autologous stem cell transplantation (ASCT) is considered. However, given that the average age of onset for DLBCL is 60 to 70 years of age, ASCT is not always possible. In refractory patients in whom ASCT is not an option, there are limited treatment options, and Polivy is intended for use in this group. Relapsed/refractory DLBCL is a rare condition as it represents only a fraction of patients with DLBCL, itself an uncommon disease. Therefore, the efficacy and safety of Polivy was supported in this submission largely by a single Phase II study. Regulatory status This is an application to register a new biological entity for Australian regulatory purposes. At the time the TGA considered this application, a similar application had been submitted in the United States of America (USA) and the European Union (EU) (see Table 1). Table 1: International regulatory status of Polivy Country Submission date Approved indication /region USA 19 December 2018 Polivy in combination with bendamustine and a rituximab product is indicated for the treatment of adult patients with relapsed
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