Australian Public Assessment Report for purified antigen fractions of inactivated split virion A/Indonesia/05/2005 (H5N1), as03 adjuvanted

December 2015

Australian Public Assessment Report for purified antigen fractions of inactivated split virion A/Indonesia/05/2005 (H5N1), AS03 adjuvanted

Proprietary Product Name: Prepandrix

Sponsor: GlaxoSmithKline Australia Pty Ltd

About the Therapeutic Goods Administration (TGA)

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  The Therapeutic Goods Administration (TGA) is part of the Australian Government Department of Health and is responsible for regulating medicines and medical devices.
  
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  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.
  
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  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.
  
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  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.
  
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  To report a problem with a medicine or medical device, please see the information on the TGA website .
  

About AusPARs

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  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.
  
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  AusPARs are prepared and published by the TGA.
  
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  An AusPAR is prepared for submissions that relate to new chemical entities, generic medicines, major variations and extensions of indications.
  
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  An AusPAR is a static document; it provides information that relates to a submission at a particular point in time.
  
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  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 2015

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 .

Contents

About AusPARs 2

Common abbreviations 5

I. Introduction to product submission 6

Submission details 6

Product background 6

Regulatory status 7

II. Quality findings 8

Introduction (if applicable) 8

Drug substance (active ingredient) 9

Drug product 9

Biopharmaceutics 10

Quality summary and conclusions 10

III. Nonclinical findings 11

Introduction 11

Pharmacology 14

Pharmacokinetics 17

Toxicology 17

Nonclinical summary and conclusions 21

IV. Clinical findings 22

Introduction 22

Pharmacokinetics 24

Pharmacodynamics 25

Dosage selection for the pivotal studies 25

Efficacy 29

Safety 40

First round benefit-risk assessment 45

First round recommendation regarding authorisation 48

Clinical questions 49

Second round evaluation 50

Second round benefit-risk assessment 53

V. Pharmacovigilance findings 54

Risk management plan 54

VI. Overall conclusion and risk/benefit assessment 63

Introduction 63

Quality 64

Nonclinical 65

Clinical 65

Risk management plan 74

Risk-benefit analysis 74

Outcome 87

Attachment 1. Extract from the Clinical Evaluation Report 87

Common abbreviations

Abbreviation	Meaning
AE	adverse event
AESI	adverse event of special interest
AS03	Adjuvant System 03
ASA	Australian Specific Annex
CMI	Consumer Medicine Information
EMA	European Medicines Agency
GD	gestational day
GMT	geometric mean titre
GSK	GlaxoSmithKline
HA	haemagglutinin
HI	hemagglutination inhibition
IM	intramuscular
ISS	Integrated Summaries of Safety
MAE	medically attended adverse event
NOCD	New Onset Chronic Disease
RMP	Risk Management Plan
RR	relative risk
PI	Product Information
pIMD	potentially immune mediated disease
SAE	serious adverse event
SCF	seroconversion factor
SCR	seroconversion rate
SPR	seroprotection rate
VRR	vaccine response rate