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PEDV Vaccine, Path to Conditional License

Meggan BandrickZoetis, VMRD, Global Biologics Research

NA PRRS ConferenceDecember 6, 2015

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Zoetis is committed to helping producers & veterinarians fight PEDv

PEDv Conditionally Licensed Vaccine* Zoetis received a USDA Conditional License

for a Porcine Epidemic Diarrhea Vaccine, Killed Virus in September, 2014. Inactivated whole-virus Contains all relevant immunizing antigens (S- and M-

proteins) Adjuvanted to help enhance immune response

Continue surveillanceUnparalleled Technical Services support and R&D expertise

*This product license is conditional. Efficacy and potency studies are in progress.

Rapid Disease Onset

Lengthy PEDv shedding

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Path to Conditional LicensePEDv appeared in the US in April 2013

Dramatic losses of neonatal pigs and corresponding severe economic impacts to swine producers were rapidly experienced across the US

USDA issued a Federal Order on June 5, 2014 mandating reporting and implementation of reasonable herd/premises management plans of SECD

Given the emergent situation and economic impact, a path for conditional license was approved by the USDA

A Conditional License allows companies to bring products to producers quickly to help protect animal health

Requirements for a Conditional License: • Reasonable Expectation of Efficacy in the target population• Full Safety Evaluation in the target population across geographic sites• Purity testing

We also conducted a Field Safety & Efficacy evaluation and sow booster serology evaluation

This product license is conditional. Efficacy and potency studies are in progress.

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EXPECTATION OF EFFICACYConditional License Requirement

Objective: to demonstrate a reasonable expectation of efficacy by ≥4-fold difference in PEDv-specific antibodies in piglets of vaccinated sows compared to non-vaccinated sows

Study Design:

Sera were collected from sows prior to each vaccination and 7 days after the 2nd vaccination (Days 0, 21, 28) and from piglets at 3 days of age

Sera from the sows and five randomly-selected piglets/litter were submitted to SDSU for fluorescent focal neutralization (FFN) antibody titer testing

Conclusions regarding safety were based on the summary of injection site observations and reported adverse events attributed to sow vaccination; Farrowing information was summarized

Presented at the AASV Meeting, Orlando, FL, March, 2015. Vicki Rapp-Gabrielson, Dan Fredrickson, Meggan Bandrick, Lucas Taylor, Tracy Ricker, Dan Coleman, Angela Pfeiffer, Chad Locke, Nicole Ideus, Michael Huether, Terri Hildebrand, Kurt Smit, Mallory Schug, Jun Zhang, Shelly Zager, John Hardham, *Data on file, Study Report No. B821R-US-14-270, Zoetis Inc.

Treatment Description Dose/Route Vaccination 1 Vaccination 2

T01 Placebo

2 mL /IM

5 weeks pre-farrow

day 0

2 weeks pre-farrow

day 21

T02 PED Vaccine, formulation 1

T03 PED Vaccine, formulation 2

T04 PED Vaccine, formulation 3

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EXPECTATION OF EFFICACY: Results & Conclusions

Vaccination induced PEDv FFN antibodies in vaccinated sows, these antibodies passively transferred to, and were detected in, their piglets;

a reasonable expectation of efficacy was established

• PEDv FFN titers of piglets born to vaccinated sows were at least 7.4 fold greater than piglets of control sows.

• The LS mean titers were all significantly higher (P < 0.0001) than T01.

• No adverse systemic reactions or adverse reproductive endpoints due to the vaccine were observed.

Three Days of Age0

10

20

30

40

50

60

70

80

90

100

PEDv FFN Antibodies in Piglet Serum

T01T02T03T04

Bac

k-tra

nsfo

rmed

LSM

tite

r * * *

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Revaccination with a single booster dose approximately 4 months after the initial 2 dose vaccination induced anamnestic serum antibody responses in all vaccinated sows.

• The sows from the efficacy study were revaccinated with a single dose of the same treatment ~4 months after initial vaccination

• Sows in all vaccinated groups (T02 – T04) had antibody titers that were 4-6 fold higher than after the initial 2 doses of the same vaccines

Presented at AASV Meeting, Orlando, FL, March, 2015. Vicki Rapp-Gabrielson, Dan Fredrickson, Meggan Bandrick, Lucas Taylor, Tracy Ricker, Dan Coleman, Angela Pfeiffer, Chad Locke, Nicole Ideus, Michael Huether, Terri Hildebrand, Kurt Smit, Mallory Schug, Jun Zhang, Shelly Zager, John Hardham, Data on file, Study Report No. B921R-US-14-397, Zoetis Inc.

Pre-revacc 7 days post 14 days post0

50

100

150

200

250

300

350

PEDv FFN in sow serum following booster vaccination ~4 months after primary series

T01 T02 T03 T04

Geo

met

ric M

ean

FFN

Tite

rFFN TITERS AFTER SOW BOOSTER VACCINATION

Not a requirement for Conditional License

Objective: to evaluate the PEDv-specific antibody response following booster vaccination at a time consistent with the recommendation for boostering prior to subsequent farrowing

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FIELD EFFICACY: PROOF OF CONCEPTNot a requirement for conditional licensure

Study Design:

This study was conducted in a commercial production facility, in the face of an acute PEDv outbreak

Generalized randomized block design with rolling enrollment: 8 blocks of 30 sows/block (10 per parity group) enrolled at weekly intervals The presence of PEDv was determined by PCR testing of pooled fecal swabs from 3-5 piglets,

collected at the time of processing.

Safety: Vaccine safety was evaluated by general health and injection site observations.

Efficacy: Reduction of pre-weaning mortality associated with PEDv was the primary outcome variable.

Presented at NA PRRSV, Chicago, IL, December, 2014. V. J. Rapp-Gabrielson, D. Fredrickson, M. Bandrick, L. Taylor, J. Marx, T. Ricker, D. Coleman, A. Pfeifer, J. Thomson, J. Zhang, S. Zager, M. Huether, J. Hardham, S. Sornsen Data on File, Study Report No. B826R-US-13-258, Zoetis Inc.

Treatment No. sows Description Dose/Route Vaccination 1 Vaccination 2T01 120 Adjuvant Placebo 2 mL/

IM5 weeks

pre-farrow, Day 02 weeks

pre-farrow, Day 21T02 120 PEDv Vaccine

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FIELD EFFICACY: Results–Litters from vaccinated sows, across

all parity groups, had a 0.6% PEDv-associated pre-weaning mortality rate compared to 6.3% in litters from placebo controls (a 90.4% relative reduction).

–Vaccinated sows had 72% fewer litters with 100% pre-weaning mortality compared to placebo controls.

–Farrowing data (number born alive, low viability, stillborn, mummies) were similar for T01 & T02.

–No abnormal systemic reactions (anorexia, lethargy, abortions) due to the vaccine were recorded.

Overall Litters WeanedTrt No. Sows Litters Weaned (%)**

T01 114 78.1%

T02 113 93.8%

Litters not weaned include not weaned for any reason*Back-transformed**The LS Mean number of piglets weaned per litter (P=0.0004)

Gilts P1-P3 P4+ All0

3

6

9

12

Back-transformed Mean* (%) Litter Pre-Wean Mortality due to PEDv

T01 Placebo T02 Vaccinates

Mea

n Pe

rcen

t

6.3%

0.6%

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FIELD EFFICACY: Economic Analysis & Conclusions

Conclusions: • The PEDv vaccine is safe for use in commercial animals • The PEDv vaccine is effective at helping reduce pre-wean mortality in face of an

acute PEDv break• The PEDv vaccine has been shown to have an economical benefit of $99.93 per

litter in commercial animals in face of an acute PEDv break1. Data on file, Query B2258Q002, Zoetis Inc.2. A comprehensive economic analysis of the adoption of an immunological alternative to physical castration by the US pork

industry: A White Paper, February 2013, page 10 Brian Buhr, Ph.D., EconAnalytics, LLC, Terrance Hurley, Ph.D., University of Minnesota, Glynn Tonsor, Ph.D., Agri-Food Analytics, LLC , Kelly Zering, Ph.D., North Carolina State University, Dennis DiPietre, Ph.D., KnowledgeVentures, LLC, Organizing Member.

3. ibid, page 26.

Vaccinated sows had an additional 1.8 pigs survive per sow farrowed1

Average cost per viable pig born of $31.052 Direct savings of $55.89 per litter

Assuming an average profit per pig sold to market of $73.583 and a 25% birth to finish mortality This may result in an additional profit of

$99.33 per litter

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Conclusions

Zoetis is committed to the swine industry for PEDv disease prevention: To meet CVB requirements for issuing a conditional license we are

working toward a fully licensed PEDv vaccineo Potency and efficacy studies in naïve pigs are ongoingo Safety testing is complete

We are continuing our evaluation of the impact of vaccination on disease controlo SN/FFN titer correlation to vaccination and protectiono Protection of non-previously exposed animalso Vaccination, feedback..

The PEDv killed virus vaccine is a tool to help reduce pre-wean mortality and PEDv disease