Australian Public Assessment Report for Trastuzumab Proprietary Product Name: Ogivri Sponsor: Alphapharm Pty Ltd March 2020 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 2020 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 OGIVRI - Trastuzumab - Alphapharm Pty Ltd - PM-2017-01084-1-4 2020 Page 2 of 30 FINAL 18 March Therapeutic Goods Administration Contents Common abbreviations _____________________________________________________ 4 I. Introduction to product submission ____________________________________ 6 Submission details ____________________________________________________________________ 6 Product background __________________________________________________________________ 7 Regulatory status _____________________________________________________________________ 8 Product Information__________________________________________________________________ 8 II. Registration time line ____________________________________________________ 8 III. Overall conclusion and risk/benefit assessment ___________________ 9 Introduction ___________________________________________________________________________ 9 Quality ________________________________________________________________________________ 13 Nonclinical ___________________________________________________________________________ 14 Clinical ________________________________________________________________________________ 14 Risk management plan ______________________________________________________________ 25 Risk-benefit analysis ________________________________________________________________ 27 Outcome ______________________________________________________________________________ 28 Attachment 1. Product Information _____________________________________ 29 AusPAR OGIVRI - Trastuzumab - Alphapharm Pty Ltd - PM-2017-01084-1-4 Page 3 of 30 FINAL 18 March 2020 Therapeutic Goods Administration Common abbreviations Abbreviation Meaning ADA Anti-drug antibody/antibodies ADCC Antibody-dependent cell-mediated cytotoxicity AE Adverse event ARTG Australian Register of Therapeutic Goods AUC Area under the curve or area under the serum concentration versus time curve AUC0- Area under the curve or area under the serum concentration ∞ versus time curve from time 0 (dosing) extrapolated to infinity AUC0-last Area under the curve or area under the serum concentration versus time curve from time 0 (dosing) to last measured concentration CHMP Committee for Medicinal Products for Human Use (EU) CI Confidence interval Cmax Maximum observed serum concentration after IV infusion (just after end of infusion) ECOG Eastern Cooperative Oncology Group EMA European Medicines Agency (EU) ErbB-2 Human epidermal growth factor receptor 2 (also known as HER2) EU European Union FDA Food and Drug Administration (US) GMP Good Manufacturing Practice HER2 Human epidermal growth factor receptor 2 HFI Hereditary fructose intolerance ICH International Conference on Harmonisation IHC Immunohistochemistry IM Intramuscular ITT Intention-to-treat AusPAR OGIVRI - Trastuzumab - Alphapharm Pty Ltd - PM-2017-01084-1-4 Page 4 of 30 FINAL 18 March 2020 Therapeutic Goods Administration Abbreviation Meaning IV Intravenous LVEF Left ventricular ejection fraction (via echocardiography) MAA Marketing Authorisation Application mAbs Monoclonal antibodies ODAC Oncologic Drugs Advisory Committee (US) ORR Objective response rate OS Overall survival pCR Pathological complete response PD Pharmacodynamic(s) PE Point estimate PEG Polymers of ethylene glycol PFS Progression free survival PI Product Information PK Pharmacokinetic(s) popPK Population pharmacokinetic(s) PRAC Pharmacovigilance Risk Assessment Committee (EU) RECIST Response Evaluation Criteria in Solid Tumours RMP Risk management plan SAE Serious adverse event SmPC Summary of Product Characteristics (EU) TEAE Treatment-emergent adverse event TTP Time to tumour progression US(A) United States (of America) AusPAR OGIVRI - Trastuzumab - Alphapharm Pty Ltd - PM-2017-01084-1-4 Page 5 of 30 FINAL 18 March 2020 Therapeutic Goods Administration I. Introduction to product submission Submission details Type of submission: Biosimilar Decision: Approved Date of decision: 5 December 2018 Date of entry onto ARTG: 11 December 2018 ARTG numbers: 288222, 288223 No ‚Black Triangle Scheme Active ingredient: Trastuzumab Product name: Ogivri Sponsor’s name and address: Alphapharm Pty Ltd PO Box R1462 Royal Exchange NSW 1225 Dose forms: Powder for injection 150 mg vial; and Powder for injection 440 mg vial with bacteriostatic water for injection vial Strength: 150 mg and 400 mg Container: Vial Pack size: 1 Approved therapeutic use: Early Breast Cancer Ogivri is indicated for the treatment of HER2-positive early breast cancer following surgery, and in association with chemotherapy and, if applicable, radiotherapy. Locally Advanced Breast Cancer Ogivri is indicated for the treatment of HER2-positive locally advanced breast cancer in combination with neoadjuvant chemotherapy followed by adjuvant OGIVRI. Metastatic Breast Cancer Ogivri is indicated for the treatment of patients with metastatic breast cancer who have tumours that overexpress HER2: AusPAR OGIVRI - Trastuzumab - Alphapharm Pty Ltd - PM-2017-01084-1-4 Page 6 of 30 FINAL 18 March 2020 Therapeutic Goods Administration a) as monotherapy for the treatment of those patients who have received one or more chemotherapy regimens for their metastatic disease; b) in combination with taxanes for the treatment of those patients who have not received chemotherapy for their metastatic disease; or c) in combination with an aromatase inhibitor for the treatment of post-menopausal patients with hormone-receptor positive metastatic breast cancer. Advanced Gastric Cancer Ogivri is indicated in combination with cisplatin and either capecitabine or 5-FU for the treatment of patients with HER2 positive advanced adenocarcinoma of the stomach or gastro- oesophageal junction who have not received prior anti-cancer treatment for their metastatic disease. Routes of administration: Intravenous Dosage: The dosage is the same as for the innovator product Herceptin trastuzumab. Product background This AusPAR describes the application by Alphapharm Pty Ltd (the sponsor) to register Ogivri trastuzumab, 150 mg powder for injection vial, and, 440 mg powder for injection vial with bacteriostatic water for injection vial for the following indication: Early Breast Cancer Ogivri is indicated for the treatment of HER2-positive early breast cancer following surgery, and in association with chemotherapy and, if applicable, radiotherapy. Locally Advanced Breast Cancer Ogivri is indicated for the treatment of HER2-positive locally advanced breast cancer in combination with neoadjuvant chemotherapy followed by adjuvant Ogivri. Metastatic Breast Cancer Ogivri is indicated for the treatment of patients with metastatic breast cancer who have tumours that overexpress HER2: a) as monotherapy for the treatment of those patients