COVID-19 vaccine town hall event

1. Other USC
Presentations on
COVID-19 Vaccines https://www.youtube.com/watch?v=guVhs5sQ21U&feature=youtu.be
Original Presentation: Sept. 17, 2020
View it anytime at:
Dec 2, 2020 12:00 PM https://dornsife.usc.edu/dornsifedialogues

2. Moderator
April W. Armstrong, MD, MPH
Associate Dean, Clinical Research
Professor of Dermatology
Director, Clinical Research Support,
Southern California CTSI
Thomas A. Buchanan, MD
Professor of Medicine Bernard J. Hanley Chair in
Medicine. Vice Dean for Research Director of the
CTSI, Co-Director, Diabetes and Obesity Research
Institute Endocrine Division Chief in the
Department of Medicine
Steven W. Chen, PharmD, FASHP, FCSHP,
FNAP
Associate Dean for Clinical Affairs
William A. and Josephine A. Heeres Chair in
Community Pharmacy Associate Professor of
Clinical Pharmacy
USC School of Pharmacy
Michael P. Dube, MD
Professor of Medicine
Associate Medical Director of the Rand
Schrader AIDS Clinic
Interim Chief, Infectious Disease Michele D. Kipke, PhD
Professor of Pediatrics
Vice-Chair of Research at CHLA
Keck School of Medicine of USC
Institute Co-Director and Director of
Community Engagement, SC CTSI
Eunjoo Pacifici, PharmD, PhD
Chair and Associate Professor of Regulatory and
Quality Sciences
USC School of Pharmacy
Director, Regulatory Knowledge and Support,
SC CTSI
Nancy Pire-Smerkanich, DRSc, MS
Assistant Professor of Regulatory and Quality Sciences
USC School of Pharmacy
Associate Director, Regulatory Knowledge and Support,
SC CTSI

3. Prospects for an effective vaccine for
prevention of COVID-19 disease
12 Nov 2020
Michael P. Dubé, MD
Professor of Medicine
Interim Chief, Division of Infectious Diseases
Keck School of Medicine, USC
Disclosure: Indirectly receiving research monies from AstraZeneca thru NIH
for vaccine research and expect to from Sanofi soon

4. https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines

5. Developers Type Notes
University of Oxford/AstraZeneca Non-Replicating Viral Vector ChAdOx1-S On hold 7 wks; resumed late Oct
CanSino Biological Inc./Beijing
Institute of Biotechnology
Non-Replicating Viral Vector Adenovirus Type 5
(Ad5)
Gamaleya Research Institute Non-Replicating Viral Vector
Adeno-based (rAd26-S+rAd5-S)
2 different vectors
Janssen Non-Replicating Viral Vector Ad26COVS1 Single shot
Moderna/NIAID mRNA nanoparticle encapsulated -20⁰C cold storage. No adjuvant
Pfizer BNT162b2 nanoparticle mRNA; full-length, P2
mutant, prefusion spike glycoprotein
-80⁰C cold storage
Sinovac Inactivated
Wuhan Institute of Biological
Products/Sinopharm
Inactivated
Beijing Institute of Biological
Products/Sinopharm
Inactivated
Novavax Recombinant SARS CoV-2 glycoprotein
nanoparticle vaccine - adjuvanted
Sanofi Recombinant Spike protein – adjuvant A S03

6. Phase III double-blind placebo-controlled trial of
AstraZeneca/Oxford Univ. recombinant adenovirus vector
vaccine expressing SARS-Co-V2 spike protein: ChAdOx1
nCoV-19
• Replication-incompetent
chimp adenovirus vector
• Also platform for MERS,
influenza, TB, Chikungunya,
Zika, MenB, plague vaccine
• Phase 1 data show high
rate of neutralizing Ab
development with 1 dose
• N=30,000 >> 44,000
• Randomized 2:1 vaccine:placebo
• Two IM doses 30 days apart
• 7 in-person visits over 2 years
• Also includes outpatient acute illness
evaluations
• Antibody testing not done as entry
criterion
• Target 35% age 65 and older
• Focus on other high-risk groups

7. Both humoral and cellular immune responses induced in
Oxford phase I/II trial
1 jab 2 jabs Natural
infection
IgG ELISA INF-γ ELISpot response to peptides
spanning the SARS-CoV-2 spike
Folegatti, Lancet 2020

9. Community engagement efforts
• CENTRAL
• Key faith leaders
• Underserved/increased risk racial
populations
• Geriatric population (assisted living)
• Occupational engagement (industries
and unions)
• Pre-existing health conditions
• Celebrity champions
• Social media
• www.coronaviruspreventionnetwork.org
• www.preventcovid.org
• LOCAL
• Satellite site at Vernon City Hall
• Smithfield Foods
• Supermarket workers
• Healthcare workers
• Assisted living residents
• Social Media
• Mass media outreach
• Collaboration with UCLA, Harbor

10. • Pfizer and Moderna are
nanoparticles with mRNA

11. Pfizer press release – 11/9/2020
• BNT162b2 nanoparticle mRNA; full-length, P2 mutant, prefusion spike protein
• Two jabs 21 days apart
• Began July 27 and has enrolled 43,538 participants; 38,955 had 2nd dose
• First interim analysis performed when 94 evaluable cases occurred
• 1o analysis of vaccine efficacy # cases of symptomatic disease 7d after 2nd dose
• “Vaccine efficacy rate above 90%”
• Final analysis planned when total 164 cases have accrued
• EUA applied for
• Plan to produce globally ≤ 50 million doses in 2020 and ≤ 1.3 billion doses in 2021
https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-announce-vaccine-candidate-against

12. • 50,000,000 Pfizer vaccine doses globally in 2020
• US comprises 4% of global population
• If distributed equitably globally, US should receive 2,000,000 doses
• There are ~17,000,000 healthcare workers in the US
• Initial supply for only a minority of US healthcare workers in phase 1a
• Not to mention first responders
• Only short-term efficacy proven
• Efficacy for prevention of severe disease not in yet
• Potential for increasing asymptomatic spread

14. Excerpts from FDA EUA procedure for SARS-CoV-2 vaccine
• An EUA can be based on an interim analysis of a clinical endpoint from a Phase 3 study
• Point estimate for a placebo-controlled efficacy trial of at least 50%, with a lower bound
of the CI around the point estimate of >30%
• Median f/u ≥2 months after completion of the full vaccination regimen to assess the
benefit-risk profile including severe COVID-19 disease
• Sufficient N of severe COVID-19 among study subjects to support low risk for vaccine-
induced ERD (5 or more severe COVID-19 cases in the placebo group)
• Adequate N to characterize reactogenicity in each protocol-defined age cohort
• >3,000 vaccine recipients followed for SAEs ≥1 month after full vaccination regimen
• Subgroup analyses of safety and efficacy stratified by prior infection status at study entry
• Continuing trials to assess long-term safety and efficacy (incl. vaccine-assoc. ERD and
waning immunity) to support vaccine licensure

15. Regulatory Challenges of COVID-19
Vaccine Development
Eunjoo Pacifici, PharmD, PhD
Nancy Pire-Smerkanich, DRSc, MS

16. Who regulates vaccines?
Office of Vaccines
Research & Review
Center for Biologics
Evaluation and Research
FDA regulates:
Food
Drugs
Biologics
Devices
Veterinary products
Cosmetics
Tobacco products

17. Authority based on Two Main laws
o Public Health Service Act (1944)
– Section 351
– Product approvals (Biologics License Application)
– Establishment licensures
o Federal Food Drug and Cosmetic Act (1938 and 1962 amendments)
– Biologics need to meet drug regulatory requirements
• IND
• GMP
• Labeling

18. Many Regulations
Gruber MF, Marshall VB. (2018) Regulation and Testing
of Vaccines. Plotkin's Vaccines.

19. Vaccine Development
Vaccines and Related Biological Products Advisory Committee 22 October 2020

20. Phase 1/2/3 combined protocol

21. Study Schema

22. Emergency Use Authorization (EUA)
o The Emergency Use Authorization (EUA) authority allows FDA to help strengthen
the nation’s public health protections against CBRN threats by facilitating the
availability and use of MCMs needed during public health emergencies.
o Under section 564 of the Federal Food, Drug, and Cosmetic Act (FD&C Act), the
FDA Commissioner may allow unapproved medical products or unapproved uses
of approved medical products to be used in an emergency to diagnose, treat, or
prevent serious or life-threatening diseases or conditions caused by CBRN threat
agents when there are no adequate, approved, and available alternatives.
o CBRN = Chemical, Biologic, Radiation or Nuclear
o MCM = Medical Counter Measure

23. EUAs Granted
Coronavirus Treatment Acceleration Program (CTAP)
o Individual and “Umbrella” EUAs for PPE
– Masks/face shields (22), respirators (26)
o In Vitro Diagnostics
– Diagnostics, Serology/Antibodies, Biomarkers (290)
o Treatments (6 Granted; 1 Withdrawn)
– Continuous Renal Replacement Therapy (CRRT) x2;
– Proprofen (sedation)
– Hydroxychlorine withdrawn when full CT data became available
– Remdesivir – EUA then full approval
– Bamlanivimab
o Vaccines - NONE
REF: https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-
framework/emergency-use-authorization#coviddrugs

24. FDA Guidance
• Clinical data to support licensure of COVID-19 vaccines
– FDA Guidance (June 2020):
o Development and Licensure of Vaccines to Prevent COVID-19
• Clinical data to support Emergency Use Authorization (EUA) of COVID-
19 vaccines
– FDA Guidance (October 2020):
o Emergency Use Authorization for Vaccines to Prevent COVID-19
• Continued evaluation of COVID-19 vaccines following licensure or EUA

25. Vaccine Clinical Trial Guidance
• Important to examine safety and effectiveness data in previously infected individuals
because pre-vaccination screening for prior infection is unlikely to occur in practice
for COVID-19 vaccines
• Effectiveness endpoints for Phase 3 trials could be:
– COVID-19 disease of any severity
– COVID-19 case definition representing more severe disease
– SARS-CoV-2 infection, whether or not symptomatic
• Clinical trials to support licensure should enroll adequate numbers of subjects
representing populations most affected by COVID-19:
– Racial and ethnic minorities
– Elderly individuals
– Individuals with medical comorbidities associated with increased risk of severe COVID-19

26. Vaccine Efficacy Endpoints
• EUA request for a COVID-19 vaccine may follow a case-driven interim
analysis from one or more clinical trials
- Clinical endpoint that assesses for direct evidence of protection against
SARS-CoV-2 infection or disease
- Vaccine Efficacy (VE) point estimate of ≥50% vs. placebo,
with an appropriately alpha- adjusted confidence interval
lower bound >30%

27. Vaccine Safety Endpoints
• General expectations are no different than those for safety data that
have supported licensure of other preventive vaccines
– Safety database of at least 3,000 subjects in relevant age groups (e.g.,
younger adults and elderly) exposed to the vaccine regimen intended for
licensure
• Safety database for COVID-19 vaccines currently in Phase 3 trials will be
substantially larger, with placebo control group
• Phase 3 trials of ~15000 participants in each arm

28. Vaccine Benefit/Risk for EUA
CBER considers a median of 2 months to be the minimum
follow-up duration that could support a favorablebenefit/risk
determination to issue an EUA for a COVID-19 vaccine
- At least 50% of participants with 2 months of follow-up for safety
and effectiveness following completion of the full vaccination
regimen

29. EUA vs Full Licensure on CTs
• Widespread deployment of a weakly effective COVID-19 vaccine could result
in more harm than good by:
– Interfering with development and evaluation of potentially better vaccines that could
have a greater impact on the COVID-19 pandemic
– Potentially allowing for even less effective vaccines to be deployed based on meeting non-
inferiority criteria for relative effectiveness (bio-creep)
– Alternative suggestion from FDA Vaccine AdComm is to use “Expanded
Access” pathway

30. Limitation of EUA/Licensure
• Data to address important benefit/risk considerations for a
COVID-19 vaccine may be limited at the time of a successful
case-driven interim or final efficacy analysis
– Durability of protective immunity elicited by the vaccine
– Effectiveness of the vaccine against the most severe and
clinically significant manifestations of COVID-19
– Potential risk of enhanced respiratory disease (ERD)
associated with waning of vaccine-elicited immunity
– Longer-term safety follow-up

31. Full Approvals – Biological License
Application (BLA)vs EUA
o Clinical
– Two WCT vs One trial
– Interim data analysis vs Full data analysis
– 2 months follow-up vs 6 months/1 year or longer
o CMC issues
– Limited Stability Data
– No Pre-Approval Inspection Required if conditions are met for
manufacturing facilities

32. FDA/CBER Considerations
 FDA must ensure that vaccines that are approved or authorized
under EUA are supported by adequate scientific and clinical data
 COVID-19 vaccines that are licensed in the US or authorized
under EUA must meet applicable legal requirements
 FDA will apply the same standards to grant a biologics license
for a COVID-19 vaccine as for other preventive vaccines

33. Thank You
SC CTSI | www.sc-ctsi.org Phone: (323) 442-4032 Email: info@sc-ctsi.org Twitter: @SoCalCTSI

34. Steven Chen, Pharm.D., FASHP, FCSHP, FNAP
Associate Dean for Clinical Affairs
William A. Heeres and Josephine A. Heeres Chair in Community Pharmacy
chens@usc.edu
Getting the
Vaccine Out:
Challenges in
distribution to
general public

35. COVID-19 vaccines challenges
• 1 vs. 2 dose series
• Products not interchangeable
• Vaccine efficacy and adverse event profile in different populations
• Distribution, varying cold-chain requirements
• Need for socially distanced vaccination practices
• Communication, education, trust

37. Pharmacy
LTC providers
Home Health
Indian Health Service
Other Federal
Entities
Public Health Clinics /
FQHCs
Hospitals
Doctor’s Office
Mobile Vaccination
Mass Vaccination
Contracted OWS
Manufacturers
Distributor
(McKesson)
Ancillary
Supplies, PPE
Partner Depots
Administration Sites
Select
commercial
partners
and Federal
entities
States
receive
allocations
Vaccine Distribution

39. :
Storage Temp: Use within:
Deep Freeze (-60 to -90o C) Exp. date (6 mos.)
Refrigeration 5 days
Room temp, undiluted 2 hours
Room temp, diluted 6 hours
Pfizer COVID-19 Vaccine
If no freezer: Procedure for re-dry icing for
up to 15-20 days in Cool Box

40. 40
Pharmacies per 10,000 People by
County in the U.S., 2015
https://doi.org/10.1371/journal.pone.0183172
In the US:
• 67,000 pharmacies, ~86% of US
population lives within 5 miles
• 5,500 hospitals
• 5,400 emergency rooms
• 1,400 community health centers
15,149

41. How often do people visit pharmacies?
• Seniors: 12-14 times per year
• Non-senior adults: 24-36 times per year

43. https://www.cdc.gov/vaccines/imz-managers/downloads/COVID-19-Vaccination-Program-Interim_Playbook.pdf
https://www.cdph.ca.gov/Programs/CID/DCDC/CDPH%20Document%20Library/COVID-19/COVID-19-Vaccination-Plan-California-Interim-
Draft_V1.0.pdf

44. Vaccine Distribution / Implementation: Next Steps
• CDC working with commercial partners and Federal entities that will receive
direct allocations for expanded access
• Identify critical priority populations for early vaccine allocation / distribution
• Onboarding / agreements with providers to receive and administer vaccine,
particularly those serving critical populations
• Ensure state data systems have processes to monitor vaccine distribution,
uptake, demand, and wastage
• Begin engaging with community stakeholders to address vaccine hesitancy

45. Overcoming Regulatory Challenges and Building
Community Trust for
SARS-CoV-2 Vaccine
Public Trust and Local Challenges
Michele D. Kipke, PhD
Professor of Pediatrics, KSOM
Co-Director, SC CTSI
Vice Chair of Research & Division Chief, Children’s Hospital Los Angeles

46. It is all about trust!
• Black and Latinx communities have higher rates of SARS-CoV-2 infection,
disease progression, and mortality. Black Americans are nearly 2.5 times
more likely to die from COVID-19 than white Americans.
• As scientists race to develop a vaccine, there is considerable skepticism
and mistrust, especially in communities of color.
• Many Black Americans remember horrific abuses in our nation’s medical
history and are concerned the past will repeat itself.
• Black Americans are less likely than white Americans to say they will get a
flu vaccine this year, and are less likely to take a first-generation SARS-
CoV-2 vaccine — 50% of Hispanic and white respondents say yes
compared to 28% of Blacks.

47. The Role of Medicine in Systems of Oppression in America (10/2/20)
Yendi Linares, MD
Ashley Bennett, MD
Children’s Hospital Los Angeles
https://mediasite.chla.usc.edu/Mediasite/Play/4ce8c88275ff4c60b8ef5e3d27f8c7f11d
For More Information About Historical
Oppression in Medicine

48. Listening Sessions & Message Development
As part of the SC CTSI and a state-wide consortium (STOP COVID-19 CA)
• Listen to the perspectives and attitudes about COVID-19 vaccine(s)
• Address concerns and knowledge gaps through education
• Tailor messages/strategies to increase vaccine uptake in targeted
communities, including:
• Latinx and Black communities in East and South Los Angeles
• Residents of Nickerson Gardens, largest housing project in Los Angeles
• Other at-risk communities throughout California (e.g., Central
California, Riverside, San Bernardino)
• Increase vaccine trial participation in these communities

49. Common Themes in Some LA Communities
• “Some believe the test is causing people to get infected.”
• “People are keeping quiet because it is too painful. It feels like a shadow
over us.”
• “We have been living a pandemic for years, it seems forever. COVID-19 is
just another pandemic we have to go through, in life.”
• “People in my community don’t like vaccines. They are forced to get their
kids vaccinated so their kids can go to school. They don’t like them.”
• “There is no way I would take a COVID vaccine if it was offered to me in
my community. I don’t trust they aren’t trying to kill us.”
• “The only way I would take a vaccine is if I were standing in line, getting
the same vaccine that rich people are getting in Beverly Hills.”

50. Q&A Session
Please submit your questions through the Q&A function or the
“Raise your hand” function.
Moderator:
April Armstrong, MD MPH
Associate Dean for Clinical Research
Professor of Dermatology
Director, Clinical Research Support, Southern California CTSI
Keck School of Medicine
University of Southern California

51. On behalf of MESH, SC CTSI and the COVID-
19 Taskforce…
Thank you for attending!
Please send any questions to Nicki Karimipour:
Nicki.Karimipour@med.usc.edu