COVID-19 Update #118 for 1/26/2022

The Department of Health and Human Services (HHS) has created a summary table of outpatient treatments of mild-to-moderate COVID-19. The table includes Paxlovid, Molnupiravir, Sotrovimab, Bamlanivimab/Etesevimab and Casirivimab/Imdevimab.
 
COVID-19 Antivirals
 
Ensovibep – a DARPin (Designed Ankyrin Repeat Protein) antiviral is being developed by Novartis and Molecular Partners as a treatment for COVID-19. DARPins are mono or multi-specific protein-based therapies. Ensovibep has three individual DARPin domains that block receptor-binding in the SARS-CoV-2 virus causing strong neutralization of the virus.

• Ensovibep is administered as a single dose IV infusion.
• In vitro testing has demonstrated high neutralization activity against all known SARS-CoV-2 variants, including the variants of concern: Alpha, Beta, Gamma, Delta and Omicron
• Novartis, with Molecular Partners announced data from 407 patients enrolled in the dose-ranging Part A of the 2,100 patient, Phase II/III, EMPATHY trial (NCT04828161), where 1.3% of patients were hospitalized or required an ER visit with ensovibep compared to 6% with placebo in vaccinated and unvaccinated, non-hospitalized symptomatic COVID-19 patients. All doses lowered viral load over eight days compared to placebo.
• Novartis, with Molecular Partners are evaluating a single dose of ensovibep 75 mg on the occurrence of hospitalizations, emergency room visits or death in COVID-19 patients enrolled in the 29-day, 1,700 patient, Part B of the Phase II/III, EMPATHY trial (NCT04828161).

 
Plitidepsin is an eEF1A2 Inhibitor being developed by PharmaMar to treat multiple myeloma. Plitidepsin demonstrated in-vitro antiviral activityagainst a coronavirus similar to SARS-CoV-2.

• Plitidepsin is administered as an intravenous infusion and given once per day for a total of 3-days.
• An in vitro study that tested the antiviral effects of plitidepsin on wild-type SARS-CoV-2 and the Alpha, Beta, Delta, Mu and Omicron variants found good activity with all variants. 

• In a 46 patient, Phase I, APLICOV-PC trial (NCT04382066), a three-day treatment with plitidepsin reduced SARS-CoV-2 viral load with a mean time to undetectable levels of 13 days in hospitalized COVID-19 patients.
• Plitidepsin is being evaluated as a treatment for COVID-19 in the 8-day, 609 patient, Phase III, NEPTUNO trial (NCT04784559).

 
The FDA expanded the EUA for remdesivir to include a three-day outpatient course in non-hospitalized patients with mild-to-moderate COVID-19 at high risk to progress to severe disease. To make administration easier, Gilead is developing GS-5245, an oral prodrug for remdesivir.
 
COVID-19 Vaccines
 
A retrospective CDC study found that patients who received a booster dose of an mRNA vaccine were less likely to develop symptomatic COVID-19 with the Delta or Omicron variants compared to patients that received two vaccine doses or were unvaccinated. Vaccination was slightly less protective against infection for the Omicron variant. A second CDC study found mRNA vaccine effectiveness after a third mRNA vaccine was 94% for Delta variant cases and 82% for Omicron variant in preventing COVID-19–associated emergency department and urgent care encounters and 94% for Delta variant cases and 90% for Omicron variant cases in preventing COVID-19–associated hospitalization. A third CDC study found the largest impact of receiving a booster dose to decrease the risk of COVID-19 infection and death were seen in 50 years and older.
 
COVID-19 Antibodies
 
The FDA limited the EUA for monoclonal antibody combinations from Lilly (bamlanivimab plus etesevimab) and Regeneron (casirivimab plus imdevimab) to only be used when the patients are likely to have been infected with or exposed to a variant that is susceptible to these treatments. This excludes use for Omicron, which is the current dominant COVID-19 variant. The FDA did not discontinue either EUA, because of the potential for use in the future. As a follow-up to the FDA’s update and last week’s restriction of the two combinations in the NIH guidelines, HHS will stop distributing bamlanivimab plus etesevimab and casirivimab plus imdevimab.
 
COVID-19 Anti-Inflammatories
 
In an 11-day, 200 patient, open-label, Phase III trial ( NCT04726098), 31.4% of patients treated with dexamethasone 6 mg once daily for 10 days had clinical worsening compared to 16.3% with dexamethasone 20 mg once daily for 5 days, followed by 10 mg once daily for additional 5 days in hospitalized Spanish patients with confirmed COVID-19 pneumonia requiring oxygen therapy.