Operation Warp Speed: Convalescent Plasma Collection Q&A

Operation Warp Speed: Convalescent Plasma Collection

Q&A Session

November 16, 2020

John WilgisVice President of Member and Corporate ServicesFlorida Hospital Association

Welcome!

Today’s Objectives

● Provide context of Operation Warp Speed and efforts to accelerate collection of Convalescent Plasma

● Share perspectives on local coordination efforts, role of Local Coordinators and various stakeholders

● Discuss role of hospitals in accelerating plasma collections, key expectations and next steps

Today’s Presenters

John Koerner, MPH, CIHLead, COVID-19 Convalescent Plasma Local Coordinator Team, Operation Warp Speed - Assistant Secretary for Preparedness and Response

Peter Marks, MD, PhD Director, Center for Biologics Evaluation and ResearchU.S. Food and Drug Administration

HHS Confidential Information – For Official Use Only – Not to be Disseminated

INFORMATION NOT RELEASABLE TO THE PUBLIC UNLESS AUTHORIZED BY LAW: This information has not been publicly disclosed and may be a privileged, confidential, deliberative, and/or pre-decisional communication. It is for internal government use only and must not be disseminated, distributed, or copied to persons not authorized to receive the information. Unauthorized disclosure may result in prosecution to the full extent of the law.

NOVEMBER 2020

Discussion on Hospital Outreach for Donor Recruitment

Convalescent Plasma

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DRAFT – PRE-DECISIONAL & DELIBERATIVE

FOR OFFICIAL USE ONLY - DO NOT DISTRIBUTE

Objectives of this discussion

Provide context of Operation Warp Speed and efforts to accelerate collection of Convalescent Plasma

Share perspectives on local coordination efforts, role of Local Coordinators and various stakeholders

Discuss role of hospitals in accelerating plasma collections, key expectations and next steps

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Operation Warp Speed overview

Ensure availability of research assays / models, clinical design and execution and manufacturing capacity expansion

Diagnostics (Dx)Support pre-clinical and clinical development, manufacturing, and distribution/access

Therapeutics (Tx)Stimulate innovation to enable rapid, multi-modal testing of COVID-19 infection and immunity

Vaccines (Vx)

Operation Warp Speed (OWS) is multi-agency USG effort conducted in collaboration with the private sector to protect the American people from

future COVID-19 devastation by providing funding, coordination, and regulatory support to enable the rapid development and distribution of

novel diagnostics, therapeutics, and vaccines

Today's focus

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Convalescent Plasma as a potential treatment to COVID-19 is a key focus area for OWS Therapeutics

Accelerate collection of COVID-19 Convalescent

plasma to meet anticipated demand and build reserve

stock for future

Use in patients via direct transfusion either immediately

or anticipation of a fall surge

Further manufacturing into HyperIG for use in clinical

trials or expanded patient use

Overall goal of effort CCP Collection enables multiple therapeutics

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Achieving goal requires two lines of effort

Accelerating plasma

collection

Collection capacity expansion

Expansion strategies to create additional capacity

in hotspot counties

Donor identification & activationBroad and targeted campaigns to mobilize potential donors

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Local Coordinators' partnerships with local stakeholders have been key to driving CCP collections

Public officials & Health depts.

Hospitals & Healthcare systems

Civic organizations & Community leaders

Blood centers & Fractionators

• Facilitating ops & mktg. support via Mayors, etc.

• Enabling CCP messaging via PSAs, contact tracers

• Enabling direct donor outreach via hospitals

• Connecting hospitals with blood centers for drives …

• Building partnerships with key members in the area

• Enabling CCP messaging via community outreach

• Facilitating operational and process support

• Supporting marketing and donor activation efforts

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Local Coordinators are deployed to help facilitate collection expansion and donor activation via engaging local stakeholders

• Amplify USG facilitated national mktg. & awareness campaign locally by activating potential donor communities

• Amplify USG facilitated donor identification and outreach

• Engage local hospitals, communities and civic organizations for donor activation

• Engage state & local agencies to identify add'lCBSA-specific opportunities to further support donor identification & activation

• Feed in learnings from other hotspots, showcase local success stories

• Ensuring impact of nationwide assets at the local level (e.g,. TFIIU website)

• Help resolve bottlenecks and local barriers with USG or state/county/city level support

• …

Collection Centers, Hospitals, Civic Orgs, Public Health Agencies etc.

• Help identify potential donors, severely hit and underserved communities

• Conduct outreach to potential donors encouraging them to donate plasma

• Provide local perspective to national team on donor sentiment and engagement

• Share insights into local donor registration and conversion context

• Help validate the site-level capacity & operations baseline, to accurately articulate progress & success stories

• Share ideas on barriers/bottlenecks at the local level that USG could remove to increase donor intake and collection throughput in one's facilities

Local Coordinators Local Stakeholders

Accelerated Collections

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~70% increase in collections to date in Wave 1 target areas

However, rate of collection increase is slowing, and incidence of eligible donors is changing

Therefore, hospitals key to continue increasing collections by helping reach out directly to eligible donors

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Identify patients that have recovered from COVID-19 (strictly within HIPAA guidelines)

Reach out to those patients to inform them about the opportunity for CCP donation

Connect / route potential donors to donate plasma at a local blood collection center

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Next steps

Review guide and follow-up with regional coordinator with questions

Confirm participation in donor recruitment for collection of CCP

Identify and quantify number of patients who are potential donors

Finalize donor communication strategy: calls / mailers etc.

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Please refer to the guide for FAQs on HIPAA, protocol to identify donors, donor communication strategy etc.

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Thank you!

COVID-19 Convalescent Plasma

Question and Answer SessionNovember 16, 2020

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Emergency Use Authorization (EUA)

• August 23, 2020: FDA issued EUA for use of COVID-19 Convalescent Plasma for the treatment of hospitalized patients with COVID-19

• Criteria for issuance of EUA:–Serious or Life-Threatening Disease or Condition–Evidence of Effectiveness: “may be effective”–Risk-Benefit Analysis–No Alternatives–https://www.fda.gov/media/97321/download

www.fda.gov

https://www.fda.gov/media/97321/download

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Summary of Available Evidence

• The totality of the evidence supports the safety and efficacy of convalescent plasma for use in the treatment of COVID-19

1. Efficacy of convalescent plasma in prior outbreaks2. Supportive pre-clinical evidence in COVID-193. Supportive evidence from small clinical trials4. Data from the US CP Expanded Access Program

www.fda.gov

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Rationale for Convalescent Plasma

• Potential efficacy of convalescent plasma in the treatment of respiratory viruses has been suggested including for

–Spanish influenza A (H1N1)–Avian influenza (H5N1)–Pandemic influenza A 2009 (H1N1pdm09)–SARS coronavirus (SARS-CoV-1), MERS coronavirus

• Best efficacy when plasma with known antibody titers used• Greatest effect on mortality generally observed when administered

early after symptom onset

www.fda.gov

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Supportive Non-Clinical Data

• SARS-CoV-2 isolates replicate efficiently in the lungs of Syrian hamsters and cause severe pathological lesions in the lungs

–Passive transfer of convalescent serum to naïve hamsters inhibited virus replication in their lungs

PNAS 2020;117:16587-16595

• Ad5-hACE2-transduced mice enabled assessment of convalescent plasma (and other therapeutics)

–Passive transfer of human CCP prevented weight loss and lung tissue histological changes, and accelerated the rate of virus clearance

Cell 2020 Jun 10 doi: 10.1016/j.cell.2020.06.010 [Epub ahead of print]

www.fda.gov

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Reports of Use of COVID-19 CP

• Early case series from the initial outbreak in China suggested potential efficacy in COVID-19

• Studies of COVID-19 CP generally fall into the following categories:

–Randomized controlled trials (RCTs)–Controlled trials based on availability of plasma, but not truly

randomized–Retrospective matched cohorts (e.g., propensity score

matched)–Case series

www.fda.gov

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US CP Expanded Access Protocol

• Single arm protocol with sites across US–IND held by Mayo Clinic, Funding from BARDA–Plasma from ARC/ABC

• Demographics and simple endpoints captured–Safety–7 day, 28 day survival of hospitalized patients

• Statistical analysis of dose response by titer explored to support demonstration of efficacy

www.fda.gov

24www.fda.gov

• By August 20, 2020‒ 2788 sites‒ 101,069 enrolled‒ 70,987 treated

US CP Expanded Access Protocol

Key aspect of protocol was providing access at community sites

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Safety Data - First 20,000Serious Adverse Events (SAE): Transfusion Reactions Reported Related Estimate (95% CI)

Mortality within four hours of transfusion 63 13 0.06% (0.04%, 0.11%)

Transfusion-Associated Circulatory Overload (TACO) 37 37 0.18% (0.13%, 0.25%)

Transfusion-Related Acute Lung Injury (TRALI) 20 20 0.10% (0.06%, 0.15%)

Severe allergic transfusion reaction 26 26 0.13% (0.09%, 0.19%)

Seven-day SAE Reports

Thrombolic or thromboembolic complication 87 32 0.16% (0.11%, 0.23%)

Sustained Hypotension 406 54 0.27% (0.21%, 0.35%)

Cardiac Events 643 74 0.37% (0.29%, 0.46%)

Seven Day Mortality Reported Estimate (95% CI)

Overall (5,000) 602 12.04% (11.17%, 12.97%)

Overall (20,000) 1,711 8.56% (8.18%, 8.95%)

Clinical Status

No ICU admission (n = 8,323) 501 6.02% (5.53%, 6.55%)

ICU admission (n = 11,468) 1,202 10.48% (9.93%, 11.06%)

No Mechanical Ventilation (n = 12,147) 749 6.17% (5.75%, 6.61%)

Mechanical Ventilation (n = 6,337) 767 12.10% (11.32%, 12.93%)

www.fda.gov

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Exploratory Efficacy Analysis

• Measurement of neutralizing antibody titer of the collected plasma units was not required so patients were expected to receive a wide range of neutralizing antibody titers

–Dose-response relationship between neutralizing antibody titers and clinical outcomes could provide an early signal for efficacy of CP

• Low and high-titer expected to be distributed (transfused) without bias among the patient population

• Analysis performed by FDA in collaboration with Mayo Clinic and a few other laboratories

–Broad Institute used a BSL-3 viral neutralization assay–Additional separate analyses reported by Mayo Clinic

www.fda.gov

27www.fda.gov

Initial Efficacy Analysis 7-day 28-day

Overall(N=4330)

Not Intub(N=2488)

Overall(N=2817)

Not Intub(N=1238)

Deaths Lower Titer 14.97% 13.99% 49.57% 49.43%

Deaths Higher Titer 13.61% 11.00% 46.21% 41.48%

Absolute Improvement

1.36% 2.99% 3.36% 7.95%

Relative Improvement

9.1% 21.4% 6.8% 16.1%

Statistical Significance

Not significant Significantp=0.03

Not significant Significantp=0.004

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Conclusions

• Reasonable to believe that COVID-19 Convalescent Plasma may be effective in the treatment of some patients with COVID-19

–Known and potential benefits of COVID-19 Convalescent Plasma outweigh the known and potential risks

• Clinical benefit is most likely in patients treated earlier in disease course with higher titer units of COVID-19 Convalescent Plasma or the equivalent

www.fda.gov

Questions?

Thank you!

Documents

Operation Warp Speed: Convalescent Plasma Collection Q&A