Monoclonal Antibodies: Updates from the Federal COVID Response
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Monoclonal Antibodies:
Updates from the Federal COVID Response
MICHAEL R ANDERSON MD MBA FAAP FCCM
GINA SMITH RN, CHEP, NHDP
JUNE 17, 2021
Office of the Assistant Secretary for Preparedness and Response
U.S. Department of Health and Human Services
UNCLASSIFIED / FOR PUBLIC DISTRIBUTION
1 Monoclonal Antibodies 101
2 Breaking News and Major Updates
Agenda 3 Administering Monoclonal Antibody Therapeutics
4 Sharing Lessons Learned
5 Resources
1
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Monoclonal Antibodies 101
2
Monoclonal antibodies (mAbs) are intended for patients with
mild to moderate COVID-19 who are at high risk of
developing severe disease
mAbs are likely to be most effective when given early in
About disease course
monoclonal Product is delivered via single IV infusion or subcutaneous
injection (for REGEN-COV ONLY)
antibodies
Early evidence appears to suggest promise of mAb products in
outpatient settings; products (bamlanivimab/etesevimab and
casirivimab/imdevimab) reduce the relative risk of
hospitalizations by up to 70% in high risk patients1,2
1. https://www.fda.gov/media/145802/download; https://www.fda.gov/media/145611/download
2. https://www.nejm.org/doi/full/10.1056/NEJMoa2035002 3
UNCLASSIFIED / FOR PUBLIC DISTRIBUTION
As of 06/03/21
Summary of COVID-19 Therapeutics
Exposed /
No Illness Asymptomatic Early Symptomatic Hospital Admission ICU Admission
Infected
Hosp. no act. Hospitalized, high Hospitalized,
Healthy, no Hospitalized, Hospitalized,
Not hospitalized, no limitations Not hospitalized, with limitations medical flow oxygen/non mechanical
infection not on oxygen on oxygen
problems invasive ventilation ventilation/ECMO
Remdesivir (BIIa1)
Monoclonal Antibodies5
• Bamlanivimab + Etesevimab
(AIIa) (Lilly)
Antiviral • Casirivimab + Imdevimab (AIIa)
therapies (RGN)
• Sotrovimab (GSK/Vir)
Dexamethasone (AI2, BI3)
Immune
Dexamethasone + remdesivir (BIII)
modulator
therapies Baricitinib4 (Lilly) +
remdesivir (BIIa)
Note: Ratings in red represent NIH treatment guideline recommendations
Rating of Recommendations: A = strong; B = moderate; C = optional
Rating of Evidence: I = one or more randomized trials without major limitations; IIa = other randomized trials or Key: FDA approved EUA issued
subgroup analyses of randomized trials; IIb = nonrandomized trials or observational cohort studies; III = expert opinion
Note: Continuous renal replacement therapy (CRRT) systems (from Baxter and Fresenius) and Propoven have also received EUAs; not included above as they are outside the Operation's mission 1.
BIIa rating only applicable for patients who require minimal supplemental oxygen; insufficient data for use in patients without oxygen requirement; 2. A1 rating for patients requiring invasive mechanical
ventilation or ECMO; 3. BI rating for hospitalized requiring supplemental oxygen; 4. In the rare circumstance corticosteroids cannot be used, baricitinib + remdesivir can be used, 5. Per Lilly's request, 4
FDA revoked the EUA for emergency use of bamlanivimab administered alone for the treatment of mild to moderate COVID-19 (on 4/16/2021)
UNCLASSIFIED / FOR PUBLIC DISTRIBUTION
Potential mechanism of action: mAbs
a) Bind to Virus b) Bind to Virus
1) Block Cell Uptake 3) Deliver to immune
Destruction
2) Block Membrane Fusion
Impede ability to replicate
Source: Nature
5
UNCLASSIFIED / FOR PUBLIC DISTRIBUTION
Three mAbs have been granted EUA for the
treatment of COVID-19 based on their potential
to reduce progression to severe disease and
hospitalization in high-risk patients
HHS/ASPR has oversight responsibility for the
fair and transparent allocation and distribution of
two of these therapies
Accelerating uptake of therapies can have a
significant public health impact
Goal: Facilitate the effective use of monoclonal
antibody therapeutics to reduce COVID-19
hospitalizations
6
UNCLASSIFIED / FOR PUBLIC DISTRIBUTION
Summary of COVID-19 mAb EUAs
Therapy EUA Issuance EUA revisions USG procured?
Bamlanivimab November 9, 2020 EUA revoked – April 16, 2021 Yes
(Eli Lilly & Co.) • Due to sustained increase of viral variants that
are resistant to bam alone
Casirivimab /Imdevimab1 November 21, 2020 EUA revised – 03/2021 Yes
(Regeneron) • Antiviral resistance
EUA revised – 05/2021
• Updated high risk criteria for patient selection
EUA revised – 06/21
• Updated with coformulation
• Updated with subcutaneous RoA as an alt. to IV
• Updated authorized dosage
Bamlanivimab February 9, 2021 EUA revised – 05/2021 Yes
/Etesevimab2 • Updated high risk criteria for patient selection
(Eli Lilly & Co.) • Antiviral resistance
Sotrovimab3 May 26, 2021 N/A No, commercially
(GSK / Vir Biotechnology) available
1. https://www.nejm.org/doi/full/10.1056/NEJMoa2035002; 2. https://www.fda.gov/media/145802/download; 3. https://www.fda.gov/media/149534/download 7
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Breaking News and
Major Updates
8
1 Eligibility criteria for the definition of patients who are high-risk
for progressing to severe COVID-19 have been expanded (effective
as of May 14, 2021)1
– Please see updated FDA factsheets for bamlanivimab/etesevimab
(administered together) and REGEN-COV for additional information
– Healthcare providers should consider the benefit-risk for an individual patient
2 CMS has increased reimbursement rates for mAb treatment
Updates for (effective as of May 6, 2021)
Sites – $450/reimbursement for mAb administration in most health care
settings
Administering – $750/reimbursement when administered in the beneficiary's home2
mAbs
3 Information for sites seeking to return EUA product
– If undamaged product needs to be returned, follow the below instructions:
• For bam and bam/ete, see The Lilly Return Goods Procedure,
detailed guidance can be found at: https://www.lillytrade.com/
• For REGEN-COV, call 844-734-6643
– Reconstituted (diluted) product SHOULD NOT be returned and should be
treated as waste per your facility's SOP
1. Refer to CDC for additional information for the treatment of mild to moderate COVID-19 in eligible patients. 2. CMS press
release: https://www.cms.gov/newsroom/press-releases/cms-increases-medicare-payment-covid-19-monoclonal-antibody-
infusions 9
UNCLASSIFIED / FOR PUBLIC DISTRIBUTIONAs of 05/14/21
Treatment eligibility
Products granted EUA for mild to moderate COVID-19 cases early in
infection, who are at high risk for progressing to severe COVID-19 and/or
hospitalization; with following criteria
• Confirmation via positive PCR or antigen test
• Treatment as soon as possible following positive viral test and within
10 days of symptom onset For your awareness (e.g., for patients not
• Patient symptomatic but not yet progressed to require eligible for treatment under EUA):
hospitalization or oxygen therapy
Treatment recommended for high-risk adult and pediatric patients (12 Monoclonal antibodies are under evaluation
years of age and older weight >40 kgs) – high-risk defined as patients who for additional indications
meet at least one of following criteria:
• Older age (≥ 65 years of age) • Neurodevelopmental disorders or Participation encouraged in clinical trials to
• Obesity or being overweight (BMI ≥ conditions that confer medical complexity assess additional drugs and indications
25) • Other medical conditions or factors (for
• Pregnancy example, race or ethnicity) may also place
• Chronic kidney disease individual patients at high risk for Clinical trial information available at
• Diabetes progression to severe COVID-19 https://combatcovid.hhs.gov/
• Immunosuppressive disease • Healthcare providers should consider
immunosuppressive treatment the benefit-risk for an individual
• Cardiovascular disease or patient. Authorization of EUA Tx is not
hypertension limited to the medical conditions or
• Chronic lung disease factors listed
• Sickle cell disease
Please reference EUA factsheets for specific treatment guidelines and
detailed definitions of high-risk patients 10
UNCLASSIFIED / FOR PUBLIC DISTRIBUTIONCDC variants of concern susceptibility
Information on variants of concern updated in Section 15 of FDA fact sheets
REGEN-COV fact sheet bamlanivimab / etesevimab fact sheet
11
UNCLASSIFIED / FOR PUBLIC DISTRIBUTIONShipments of bam/ete and ete alone to 9 states paused due to Beta
(B.1.351) and Gamma (P.1) variant prevalence
• CDC has identified that the combined frequency of Beta variant (B.1.351, originally identified in South
Africa) and Gamma variant (P.1, originally identified in Brazil) are circulating with increasing frequency
in 9 states
• Results from in vitro studies suggest that:
– Bam / ete administered together are not active against either Beta (B.1.351) or Gamma (P.1) variants
– REGEN-COV is likely to retain activity against Beta (B.1.351) and Gamma (P.1) variants
• Distribution of bam / ete together and etesevimab alone (to pair with existing supply of bamlanivimab) have
been paused to AZ, CA, FL, IL, IN, MA, OR, RI, WA
• FDA recommends that health care providers in these states use REGEN-COV until further notice, which
can be ordered directly from Amerisource Bergen
Please contact COVID19Therapeutics@hhs.gov with any questions
12
UNCLASSIFIED / FOR PUBLIC DISTRIBUTION The NIH has strongly recommended (AIIa) the following for
use in non-hospitalized COVID-19 patients:
– Casirivimab + imdevimab (Regeneron)
COVID-19
– Bamlanivimab + etesevimab (Eli Lilly)
treatment
guidelines Updated NIH COVID-19 guidelines can be found at:
https://www.covid19treatmentguidelines.nih.gov/statement-on-
anti-sars-cov-2-monoclonal-antibodies-eua/
13
UNCLASSIFIED / FOR PUBLIC DISTRIBUTION Sotrovimab (GSK / Vir Biotechnology) authorized for the
treatment of mild to moderate COVID-19
NOT distributed by USG
commercially available therapy
FDA authorizes Please refer to the following for more information:
additional mAb for – FDA fact sheet and EUA Letter of authorization
treatment of COVID-19 – FDA press release
– COMET-ICE clinical trial
As of May 26, 2021
For additional information and approved materials, including
information about ordering, please refer to the Sotrovimab
webpage
Please contact the GSK COVID Contact Center if you have
further questions: 1-866-GSK-COVID (1-866-475-2684)
14
UNCLASSIFIED / FOR PUBLIC DISTRIBUTIONUpdated EUA for REGEN-COV™ (casirivimab and imdevimab)
Effective June 3, 2021 the FDA has authorized under emergency use a
lower dose of REGEN-COV (600mg casirivimab and 600mg
imdevimab), which is half the dose originally authorized.
REGEN-COV should be administered by intravenous (IV) infusion;
subcutaneous injections are an alternative when IV infusion is not
feasible and would lead to a delay in treatment.
Single vial of co-formulated product now available to order via
AmerisourceBergen (as of June 10, 2021).
– Single vial represents one full, complete treatment at the lower
authorized dose
Please contact Regeneron Medical Affairs with any questions about using
existing inventory to treat patients at 1-844-734-6643
15
UNCLASSIFIED / FOR PUBLIC DISTRIBUTIONResults from REGEN-COV randomized Ph3 trial | Preprint posted May 21, 2021 Methodology Ph3 randomized clinical trial of COVID-19 outpatients with ≥ 1 risk factors for severe disease (n = 4,057)1 Patients randomized to a single treatment of IV placebo, or various doses of REGEN-COV, and followed for 28 days Key Findings 2400mg and 1200mg doses significantly reduced Covid-19-related hospitalization or all-cause death compared to placebo (71.3% reduction [p
Administering Monoclonal
Antibody Therapeutics
17Administration can occur across a wide variety of models
Hospital Ambulatory center Nursing homes Mobile sites Home
• Hospital-based • Infusion centers • Skilled nursing • Bus/trailer • At patient's home
infusion centers • Urgent care facilities • Other mobile
• Emergency clinics • Long-term care sites
departments • Dialysis centers facilities
• Converted space • Alternate care
within hospital for sites
COVID infusion
• Alternate care
sites
Information support via https://combatcovid.hhs.gov/
Materials include links to EUA criteria, consolidated playbooks & educational materials
18
UNCLASSIFIED / FOR PUBLIC DISTRIBUTIONSharing Lessons Learned
1920
The Essentials
Lessons Learned From
Federal Infusion Site :
Space
El Centro
Medical Center
Staffing
Stuff
UNCLASSIFIED / FOR PUBLIC DISTRIBUTIONRefrigerator
Vent
Laundry
Table
EMR
4 3 2 1
Table
Medication
El Centro Regional Medical
Trash
Sink
Prep Area EMR
Staff Exit
Doffing
Center Site Set-up
Area
Staff
Staff
Hot Zone
Patient Flow
Hospital Information
Staff Entrance
Patient Flow Staff
Staff
• Total Inpatient Count: 171 Donning
• COVID-19 Inpatient Count: 117 EMR
Area
HVAC
5 6 7 8 PPE
Electric Med Supply
Service
Table
Seating Staff Seating
Seating
UNCLASSIFIED / FOR PUBLIC DISTRIBUTION Have a plan
Make it scalable
Safety first
Keys to Success
Maximize resources
Document your plan successes and gaps
Be ready to do it again
22
UNCLASSIFIED / FOR PUBLIC DISTRIBUTIONResources
237
Updated factsheets and resources available for
providers
Fact sheets are available in English and Spanish at https://combatcovid.hhs.gov/hcp/resources
Please share with the providers in your network.
24
UNCLASSIFIED / FOR PUBLIC DISTRIBUTIONIn the
spotlight:
updated
How to Use this Toolkit:
mAb Digital
Monoclonal Antibody Therapeutics Digital Toolkit contains
Toolkit messages you can share on your social media channels
– Messages available for Twitter, Instagram, and Facebook
Please either copy these messages directly or customize them to
reach your appropriate audience
Toolkit available at phe.gov
13
UNCLASSIFIED / FOR PUBLIC DISTRIBUTIONOffice Call Sessions HHS / ASPR Allocation, Distribution,
Administration of COVID-19 Therapeutics
– New update: 1x/week office call sessions
– Next call: Thu, June 17, 2:00-2:30PM EST
– Zoom link: https://bit.ly/3rfRv4E
Meeting ID: 160 432 9034
Passcode: 897674
Upcoming
webinars Weekly Stakeholder Update Calls
– Next call: Wed, June 23, 3.15-4:00PM EST
– Send email to ASPRstakeholder@hhs.gov for inclusion
Contact the Federal COVID-19 Response Team:
COVID19Therapeutics@hhs.gov
26
UNCLASSIFIED / FOR PUBLIC DISTRIBUTIONProduct resources
HHSProtect Therapeutics Dashboard
https://protect.hhs.gov/workspace/module/view/latest/ri.workshop.
Helpful main.module.084a09b4-bcd0-4a6b-817a-90afb7a3cd1d
information Direct Ordering Link via ABC
https://app.smartsheet.com/b/form/255d164d67834793b4ab549e1
and 60941e8
resources Guidance for Returning Product
(I/II) - For bam and bam/ete, see The Lilly Return Goods
Procedure; detailed guidance can be found at:
https://www.lillytrade.com/
- For REGEN-COV, call 844-734-6643
27
UNCLASSIFIED / FOR PUBLIC DISTRIBUTIONInformational resources:
HHS Website: https://combatcovid.hhs.gov/
HHS/ASPR Website: https://www.phe.gov
Helpful ASPR Regional Teams
information - Consult the ASPR Regional Team in your area for questions
and regarding COVID-19 medical countermeasures
resources ASPR TRACIE general hurricane resources
(II/II) HRSA Uninsured Program fact sheet
Updated information sheets and resources for providers in
English and Spanish https://combatcovid.hhs.gov/hcp/resources
28
UNCLASSIFIED / FOR PUBLIC DISTRIBUTIONThank you! UNCLASSIFIED / FOR PUBLIC DISTRIBUTION
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