COVID-19 Update #48 for 10/27/2020

COVID-19 Antivirals
 
AT-527 is an antiviral being developed by Atea Pharmaceuticals to treat Hepatitis C. AT-527 is a purine nucleotide prodrug that inhibits viral replication by interfering with viral RNA polymerase. The drug has demonstrated in vitro and in vivo antiviral activity against enveloped single-stranded RNA viruses, such as human flaviviruses and coronaviruses. Due to activity on coronaviruses, Atea began developing the drug as a treatment for COVID-19. Roche licensed development and marketing rights for AT-527 outside the U.S. 

• AT-527 is an oral drug given once on day one, then twice a day for a total of 5-days
• Atea is evaluating AT-527 in a 190 patient, Phase II trial (NCT04396106) in hospitalized patients 45 to 80 with moderate COVID-19.
• A Phase III trial is planned in 1Q21.

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
• PharmaMar announced that in a 45 patient, Phase I trial (NCT04382066), treatment with plitidepsin reduced viral load in hospitalized COVID-19 patients and all patients were symptom free at the 30-day trial visit
• A Phase III trial is being planned.​

The FDA approved remdesivir (Veklury, Gilead), on 10/22/2020, for the treatment of hospitalized COVID-19 patients that are 12 and up and weigh at least 40 kg (88.2 lbs). The FDA issued a new EUA for remdesivir for hospitalized children age 12 and older that weigh at least 3.5 kg (7.7 lbs) but less than 40 kg, and in children under age 12 that weigh at least 3.5 kg.
 
Convalescent Plasma 
 
In the 28-day, 464 patient, open-label, PLACID trial, treatment with convalescent plasma did not reduce progression to severe disease or all-cause mortality (19% vs 18%), despite an almost 20% greater conversion to a negative SARS-CoV-2 test on day seven in hospitalized Indian patients with moderate COVID-19. Patients in the trial were treated with antivirals (hydroxychloroquine, remdesivir, lopinavir/ritonavir, oseltamivir), broad spectrum antibiotics and immunomodulators (steroids, tocilizumab).
 
COVID-19 Vaccines
 
The FDA allowed the Phase III trial for AstraZeneca’s coronavirus vaccine, AZD1222, to resume in the US, on 10/23/2020 after an FDA review of all safety data concluded the vaccine was safe.
 
Johnson & Johnson will resume the Phase III ESEMBLE trial in October 2020, after a Data Safety and Monitoring Board review found no evidence that COVID-19 vaccine candidate, Ad26.COV2-S, caused a serious medical event experienced by one study participant.
 
COVID-19 Monoclonal Antibodies
 
Lilly announced that NIAID discontinued the Phase III, ACTIV-3 trial (NCT04501978), when an interim analysis did not find an improvement when bamlanivimab was added to remdesivir compared to remdesivir alone in hospitalized patients with COVID-19.