Influenza A (H1N1) Vaccine

Vaccines and Related Biological Products Advisory Committee Meeting, 23 July 2009

Raburn Mallory, M.D.

ProprietaryVaccines and Related Biological Products Advisory Committee meeting, 23July 2009, Gaithersburg MD

22

Overview

Influenza A (H1N1) 2009 Monovalent Vaccine Live, Intranasal

Clinical studies planned and data availability

Manufacturing plans and vaccine availability

Vaccines and Related Biological Products Advisory Committee meeting, 23July 2009, Gaithersburg MD

Proprietary

33

MedImmune’s 2009 monovalent live influenza A (H1N1) vaccine

Intranasal delivery using a pre-filled single dose AccuSpray™ device 0.2 mL/dose (0.1 mL in each nostril) Contains no preservative or adjuvants

Dose is fixed at 107±0.5 FFU/strain Clinical efficacy studies conducted with trivalent seasonal vaccine,

FluMist, used to establish dose for H1N1 monovalent vaccine

FluMist replicates intranasally to generate a broad immune response Cellular Humoral Mucosal

High levels of efficacy seen in studies with trivalent FluMist HAI titers not correlated with protection

ProprietaryVaccines and Related Biological Products Advisory Committee meeting, 23July 2009, Gaithersburg MD

44

Clinical studies of our H1N1 vaccine are based on annual strain change procedure

7 previous annual clinical studies conducted in adults to incorporate new strains into trivalent seasonal vaccine, FluMist Safety from studies used to allow strain change to proceed

Two concurrent placebo-controlled clinical studies planned MI-CP215: Healthy adults 18-49 years of age (n = 300) MI-CP217: Healthy children 2-17 years of age (n = 300)

Design and randomization 2 dose schedule (107±0.5 FFU/dose) delivered 1 month apart Subjects randomized 4:1 (vaccine:placebo) Subjects randomized 1:1 to have blood drawn 14 or 28 days after first dose

Objectives Demonstrate attenuation by evaluating fever rates Evaluate solicited symptoms and adverse events Evaluate serum immune responses after each dose

ProprietaryVaccines and Related Biological Products Advisory Committee meeting, 23July 2009, Gaithersburg MD

55

Timing of data availability from studies*

ProprietaryVaccines and Related Biological Products Advisory Committee meeting, 23July 2009, Gaithersburg MD

FDA submission Content of submission Adult data

availablePediatric data available

1 Day 8 safety data after Dose 1 8 Sept 2009 14 Sept 2009

2 Day 15 immunogenicity data after Dose 1 18 Sept 2009 23 Sept 2009

3 Day 29 immunogenicity data after Dose 1 Day 8 safety data after Dose 2

12 Oct 2009 16 Oct 2009

4 Day 29 immunogenicity data after Dose 2 2 Nov 2009 9 Nov 2009

* Timing reflects best case scenario of first subject in on August 17 th and no unexpected events occurring during study conduct or data analysis

6

Manufacturing progress and key regulatory milestones

A 6:2 reassortant virus made using reverse genetics 11 May 2009 23 separate variants evaluated

Master virus seed selected for commercial manufacture 25 June 2009 Yields appear consistent with normal seasonal strains Antigenically similar to CDC recommended strain

Commercial scale manufacturing initiated 03 July 2009

Key regulatory milestones Submission of strain change supplement Review and release of H1N1 lots Review and approval of second high speed fill line

7

Timing of vaccine availability from manufacturing*

Projected availability of influenza A (H1N1) bulk and filled doses by monthMillions of doses, cumulative

Vaccine availability limited by delivery device supply constraints Finished product capacity = ~40M filled doses

Limitation is availability of sprayers (from now until March 2010) Bulk capacity at current growth rates = ~200M doses

* Availability of doses is based on current manufacturing schedule for having QC released doses available and is not linked to FDA release

10

42

95

143

179196 205 205

6 14 24 32 34 38 41

0

50

100

150

200

250Bulk doses released

Filled doses released

Aug Sept Oct Nov Dec Jan Feb Mar

Fill line 2 approval

88

Acknowledgements

Proprietary

This project has been funded in whole or in part with Federal Funds from the HHS/ASPR/BARDA, under Contract No. HHSO100200900002I

The content of this publication does not necessarily reflect the view or policies of the Department of Health and Human Services, nor does the mention of the trade names, commercial products or organizations imply endorsement by the U.S. Government.

Vaccines and Related Biological Products Advisory Committee meeting, 23July 2009, Gaithersburg MD