COVID-19 Update #47 for 10/22/2020

COVID-19 Antivirals
 
An unpublished, unreviewed report from the WHO sponsored, 11,266 patient, Phase II/III SOLIDARITY trial, did not find an improvement in hospitalized COVID-19 patients treated with remdesivir, hydroxychloroquine, lopinavir or interferon compared to no drug in mortality, initiation of ventilation or duration of hospital stay. A physician reviewer speculated that remdesivir may be more effective when given early in the infection to patients at high risk for progression.
 
Leronlimab is a monoclonal antibody that blocks the CCR5 chemokine receptor, which results in an inhibition of a virus’ ability to enter leukocytes. Leronlimab was originally developed by CytoDyn as a treatment for HIV-1 infection.

• Among 23 hospitalized severe or critical COVID-19 patients that were treated with leronlimab through a compassionate use protocol, 17 had recovered by day 30, two were still hospitalized and four died. Most patients also received or had received convalescent plasma, hydroxychloroquine, steroids, tocilizumab, remdesivir, sarilumab and/or selinexor. 
• CytoDyn is evaluating leronlimab, as a treatment for mild-to-moderate COVID-19 in a 14-day, 86 patient, Phase II trial (NCT04343651).
• CytoDyn is evaluating leronlimab, as a treatment for severe or critical COVID-19 in a 28-day, 390 patient, Phase IIb/III trial (NCT04347239).

COVID-19 Anti-Inflammatories
 
NIH will evaluate the effect of three anti-inflammatories on suppressing cytokine storm in COVID-19 patients in the 2,100 Patient, Phase III ACTIV-1 IM trial. The drugs that will be used in ACTIV-1 IM include TNF blocker, infliximab (Remicade, J&J); the CTLA-4 immunoglobulin, abatacept (Orencia, BMS); and the investigational CCR2/CCR5 agonist cenicriviroc (AbbVie).
 
In a 126 patient, Phase II, Italian trial (NCT04346355), treatment with tocilizumab did not reduce intensive care admission with invasive mechanical ventilation, death from all causes, or clinical aggravation compared to placebo in patients with early-stage COVID-19 pneumonia.
 
In a 131 patient, Phase II, French trial (NCT04331808), treatment with tocilizumab did not improve clinical progression at day 4, but did reduce death or the need for high-flow oxygen or ventilation at day 14 (24% vs. 36%) compared to placebo in patients with moderate-to-severe COVID-19 pneumonia.
 
A 3,924 patient retrospective U.S. analysis found a lower risk for death in 433 patients that received tocilizumab compared with those not treated with tocilizumab in critically ill COVID-19 patients.
 
In a 243 patient, Phase III, U.S. trial (NCT04356937), treatment with tocilizumab did not reduce intubation or death compared to placebo in patients with severe COVID-19.