COVID-19 Update #46 for 10/16/2020

COVID-19 Monoclonal Antibodies
 
BARDA has provided a $486 million Project Warp Speed grant to AstraZeneca to evaluate the long-acting monoclonal antibody combination, AZD7442, in two Phase III trials. A 5,000 patient trial will evaluate AZD7442 to prevent COVID-19 for up to 12 months and a 1,100 patient trial will evaluate the antibody as post-exposure prophylaxis. AstraZeneca will supply up to 100,000 doses by the end of 2020 and the US can acquire an additional one million doses in 2021 under a separate agreement.
 
NIAID is comparing bamlanivimab plus remdesivir to remdesivir alone in the treatment of hospitalized patients with COVID-19 in the 10,000 patient, Phase III, ACTIV-3 trial (NCT04501978). The trial was initiated in August 2020, but temporarily paused in October 2020 on the recommendation of a data and safety monitoring board to allow time to review safety data. The FDA issued a violation notice to Lilly due to quality review issues, which would need to be fixed, to be in compliance with manufacturing standards for authorization of a drug.
 
COVID-19 Vaccines
 
Vaxart is developing the non-replicating adenovirus type-5 (Ad5) viral vector DNA virus, VXA-CoV2-1.

• VXA-CoV2-1 is administered as an oral tablet that can be stored at room temperature.
• Two doses of the vaccines are given 29-days apart.
• Vaxart is evaluating the safety and immunogenicity of a high and low dose of VXA-CoV2-1 in a 48-patient Phase I trial (NCT04563702).

J&J has temporarily paused the Phase III ENSEMBLE trial, due to an unexplained illness in a study participant.
 
In a 195 patient, Phase I trial (NCT04368728), two vaccine candidates (BNT162b1 and BNT162b2) were tested in healthy adults. Patients that received BNT162b2 had a lower incidence and severity of systemic reactions than BNT162b1. No safety issues were identified, but most participants reported mild to moderate injection site pain. Tiredness, headaches and fever was reported after the second dose. Both vaccines elicited antibody levels one-month after a second dose of vaccine that were greater than levels seen in a group of recovered COVID-19 patients. 
 
COVID-19 Treatments
 
Risankizumab (Skyrizi, Boehringer Ingelheim and AbbVie) is a monoclonal antibody approved for the treatment of severe plaque psoriasis.

• NIAID is comparing risankizumab plus remdesivir to remdesivir alone in the treatment of hospitalized patients with COVID-19 in the 200 patient, Phase II, BET-A trial (NCT04583956).

Lenzilumab is a monoclonal antibody that neutralizes granulocyte macrophage colony stimulating factor (GM-CSF). The drug is being developed by Humanigen as a treatment for Chronic Myelomonocytic Leukemia and Large B-cell Lymphoma.

• Humanigen is investigating lenzilumab as a treatment for cytokine storm in COVID-19 patients with severe or critical COVID-19 pneumonia in a 300 patient, Phase III trial.
• NIAID is comparing lenzilumab plus remdesivir to remdesivir alone in the treatment of hospitalized patients with COVID-19 in the 200 patient, Phase II, BET-B trial (NCT04583969).

Molnupiravir (MK-4482) is a ribonucleoside analog that inhibits the replication of multiple RNA viruses including SARS-CoV-2. Molnupiravir is an oral drug given twice a day for 5-days.

• Merck is evaluating molnupiravir as a treatment of hospitalized patients with COVID-19 in a 1,300 patient, Phase II/III trial (NCT04575584).
• Merck is evaluating molnupiravir as a treatment of non-hospitalized patients with COVID-19 in a 1,450 patient, Phase II/III trial (NCT04575597.

NIH Treatment Guidelines 
 
The NIH provides guidelines for the treatment of patients with COVID-19 that are continuously updated. A list of updates and recommendations by date of publication are provided to help health care practitioners stay current. The guidelines include an Overview of Therapeutic Management of Patients with COVID-19, based on disease severity. There is also a review of evidence that supports or refutes the use of therapies and a recommendation by NIH for or against use of the therapies.
 
Current treatment recommendations are organized by severity of disease in an easy-to-use graphic.

• Non-hospitalized or hospitalized patients not on supplemental oxygen should not receive remdesivir or dexamethasone
• Hospitalized patients requiring supplemental oxygen, but not high flow oxygen or ventilation should receive remdesivir for five days. The duration can be extended for up to ten days and dexamethasone added. Dexamethasone alone can be used if remdesivir is not available.
• Hospitalized patients requiring high-flow oxygen or non-invasive ventilation should receive 5-10 days of remdesivir and dexamethasone or dexamethasone for up to ten days
• Hospitalized patients requiring mechanical ventilation or ECMO dexamethasone for up to ten days or 5-10 days of remdesivir and dexamethasone in patients that have recently been intubated.​