DASON COVID-19 Weekly Treatment Literature Update 7/31/2020 Prepared by: Angelina Davis, PharmD, MS, April Dyer, PharmD, MBA, MSCR, Elizabeth Dodds Ashley, PharmD, MHS, Melissa Johnson, PharmD, MHS, S. Shaefer Spires, MD, Travis Jones, PharmD

The following summarizes key literature pertaining to treatment of COVID-19 during the past week. *Note: some of the data discussed below may be in pre-print form that has not yet been peer-reviewed. We have noted some discrepancies in some of this data, and final printed versions may ultimately differ from what is shown here. We will update as soon as possible; caution is advised when interpreting this literature.

NIH Guideline Updates On Friday, July 24th and Thursday June 30th, the NIH updated treatment guidelines. The full guideline document can be found at this link: https://files.covid19treatmentguidelines.nih.gov/guidelines/covid19treatmentguidelines.pdf These are also reflected in our summary table of the NIH treatment guidelines that can be found here: https://dason.medicine.duke.edu/sites/dason.medicine.duke.edu/files/nih_covid- 19_treatment_guideline_updates_7-24-20.pdf

The most recent change on July 30th included expanding the list of that can be used. , , and are all considered alternatives when is in short supply.

The July 24th modification was to clarify oxygen requirements for remdesivir patients and further refine considerations for situations in which remdesivir is in short supply. Patients are not separated into those who are on supplemental oxygen alone and those on high-flow oxygen, mechanical ventilation or ECMO. The updated guideline now reads:

Recommendation for Prioritizing Limited Supplies of Remdesivir • Because remdesivir supplies are limited, the Panel recommends that remdesivir be prioritized for use in hospitalized patients with COVID-19 who require supplemental oxygen but who are not on high-flow oxygen, noninvasive ventilation, mechanical ventilation, or ECMO (BI).

Recommendation for Patients with COVID-19 Who Are on Supplemental Oxygen but Who Do Not Require High- Flow Oxygen, Noninvasive or Invasive Mechanical Ventilation, or ECMO • The Panel recommends using remdesivir for 5 days or until hospital discharge, whichever comes first (AI). • If a patient who is on supplemental oxygen while receiving remdesivir progresses to requiring high-flow oxygen, noninvasive or invasive mechanical ventilation, or ECMO, the course of remdesivir should be completed.

Recommendation for Patients with COVID-19 Who Require High-Flow Oxygen, Noninvasive Ventilation, Mechanical Ventilation, or ECMO • Because there is uncertainty regarding whether starting remdesivir confers clinical benefit in these groups of patients, the Panel cannot make a recommendation either for or against starting remdesivir.

2 Other Treatment Updates The FDA has updated the fact sheets for remdesivir that are to be supplied to providers and patients under the conditions of the EUA. Those updated fact sheets, which feature the new brand name, VEKLURY, can be found at these links: Fact Sheet for Healthcare Providers: https://www.gilead.com/-/media/files/pdfs/remdesivir/eua-fact-sheet- for-hcps.pdf?la=en&hash=D4229149DCD2FF6B7E83F4062C4601BB

Fact Sheet for Patients and Caregivers: https://www.gilead.com/-/media/files/pdfs/remdesivir/eua-fact- sheet-for-patients-and-caregivers.pdf?la=en&hash=45C9661BC70F1E1F58B53781B748AC5C

Fact Sheet for Patients and Caregivers (Spanish Language): https://www.gilead.com/- /media/files/pdfs/remdesivir/eua-fact-sheet-for-patients-and-caregivers_spanish- language.pdf?la=en&hash=F63F3136CF8A8B2EB21F4A3CEFDB654B

Tocilizumab update: In a press release earlier this week, provided the initial results of the COVACTA trial from Roche were announced. Tocilizumab plus standard of care did not meet the pre-specified endpoing of improvement on a clinical status scale compared with standard of care alone. Similarly, there was no mortaility benefit. Earlier time to hospital discharge was reported, but could not be considered statistically significant. The full press release can be read here: https://www.roche.com/media/releases/med-cor-2020-07-29.htm

New Literature This Week

Treatment Summary Tables The remdesivir summary table with the information of published studies to date can be found at this link: https://dason.medicine.duke.edu/summary-recent-clinical-data-use-remdesivir-covid-19

The hydroxychloroquine summary table is available at this link: https://dason.medicine.duke.edu/summary-recent- clinical-data-use-hydroxychloroquine-and-chloroquine-covid-19

The tocilizumab summary table with the information of published studies to date can be found at this link: https://dason.medicine.duke.edu/summary-recent-clinical-data-use-tocilizumab-covid-19

FAQs All FAQs available here: https://dason.medicine.duke.edu/covid-19-novel-coronavirus-resources