Remdesivir – Nucleotide analogue RNA polymerase inhibitor Aviptadil (RLF-100) is a synthetic human Vasoactive Intestinal Polypeptide. Aviptadil blocks the replication of the SARS coronavirus in human lung cells and monocytes. The drug has been in clinical trials since 2001 and was unsuccessfully evaluated for Acute Respiratory Distress Syndrome and Pulmonary Arterial Hypertension.
  • The FDA has granted aviptadil Fast Track status 
  • Aviptadil is available under an Expanded Access Protocol (NCT04453839) for the treatment of patients with COVID-19 and Respiratory Failure
  • NeuroRx is evaluating inhaled aviptadil for the treatment of moderate and severe COVID-19 patients who have not yet developed respiratory failure in a 288 patient, Phase II/III trial (NCT04360096)
  • NeuroRx is evaluating intravenous aviptadil for the treatment of hospitalized patients with a Critical COVID-19 infection and respiratory failure in a 144 patient, Phase II trial (NCT04311697)
  • An unpublished case study describes a double lung transplant patient that developed a COVID-19 infection with respiratory failure. The patient received three intravenous infusions of aviptadil and saw improvement within 24 hours of the third infusion. The patient was discharged home on room air one week later.
  • NeuroRx  has said that similar results to the case study have been seen in 15 additional patients treated with aviptadil under the Expanded Access Protocol.
Chloroquine and Hydroxychloroquine were shown in vivo to increase endosomal pH required for virus/ cell fusion, as well as interfering with the glycosylation of cellular receptors. The drugs have been evaluated as treatment or prophylaxis in several trials, but not shown to be beneficial for either use. Due to the controversial nature of the drugs, we have provided a dedicated page to summarize what is known about the use of chloroquine and hydroxychloroquine in the treatment or prevention of COVID-19. NIH recommends against the use of chloroquine, hydroxychloroquine or hydroxychloroquine plus azithromycin for the treatment of COVID-19, except as part of a clinical trial.

CPI-006 is a monoclonal antibody for CD73 that activates lymphocytes, induces the production of antigen-specific immunoglobulin from B cells and increases levels of CD4+ and CD8+ cells. CPI-006 is being developed by Corvus Pharmaceuticals as a cancer treatment.
  • Corvus is evaluating a single dose of CPI-006 as a treatment of mild to moderate COVID-19, in a 30 patient, Phase I, dose-ranging trial (NCT03454451).
  • An unpublished report describes how CPI-006 induced a rise in anti-SARS-CoV-2 antibodies at 7-days that continued to increase through day 56. ​
  • Corvus announced data from 15 patients in the study that supported an increase in anti-SARS-CoV-2 antibodies through day 56 and an increase in B cell activation.
CYNK-001 is an allogeneic, natural killer cell therapy derived from placental hematopoietic stem cells. Natural killer cells limit virus replication by killing virus infected cells. CYNK-001 is being developed by Celularity as a chemotherapy agent. Celularity has an agreement with Sorrento Therapeutics for rapid scale up of manufacturing, if clinical trials demonstrate a benefit.
  • Celularity is evaluating CYNK-001 as a treatment for COVID-19 in an 86 patient, Phase I/II trial (NCT04365101).
Favipiravir - inhibits RNA-dependent RNA polymerase (RdRp). The drug was approved in Japan in 2014 as an influenza treatment when other influenza treatments failed. Favipiravir is not available in the U.S. or Europe. 
  • There are currently no well-designed trials evaluating favipiravir in the treatment of COVID-19.
  • Fujita Health University researchers announced that in an 89 patient trial, treatment with favipiravir did not improve COVID-19 symptoms compared to placebo in patients with early-stage COVID-19.
  • Glenmark Pharmaceuticals announced that in a 150 patient, open-label, Indian Phase III trial, treatment with favipiravir added to supportive care resulted in 28.6% faster viral clearance and a 40% faster attainment of clinical cure compared to supportive care alone in patients with mild to moderate COVID-19. Patients were initiated on favipiravir within 48-hours of a positive test. Glenmark did not specify whether other antivirals were included in standard supportive care in India.
  • Interim results from 60 patients enrolled in a Russian COVID-19 trial, suggested that on day 5, treatment with favipiravir cleared SARS-CoV-2 in 62.5% of patients compared to 30% of patients on standard of care. There was no difference in clearance by day 10 (92.5% vs 80%). Most patients in the standard of care group received hydroxychloroquine, chloroquine or lopinavir/ritonavir. Standard of care treatment was not described, but included antibiotics, anticoagulants and/or immunosuppressants, as well as symptomatic treatment. Body temperature normalized 2 days earlier with favipiravir (2 days vs 4 days), but there was no difference in chest CT scan.
  • Toyama announced that 156 patient, Phase III trial, patients treated with favipiravir cleared SARS-CoV 2 viral RNA in 11.9 days compared to 14.7 days with placebo in Japanese patients with COVID-19 and non-severe pneumonia.
Galidesivir is an adenosine nucleoside analog that blocks viral RNA polymerase. The drug was originally being developed as a treatment for yellow fever. A computer model suggested that galidesivir would bind to the RNA-dependent RNA polymerase of SARS-CoV-2 and potentially be a treatment for COVID-19. BARDA and NIAID are providing funds for the development of galidesivir. Granulocyte colony-stimulating factor (G-CSF) was evaluated as a treatment for COVID-19 in a Chinese trial. G-CSF increases peripheral blood leukocyte and lymphocyte and was theorized to be beneficial in COVID-19 patients with lymphopenia. Filgrastim (Neupogen, Amgen) is a G-CSF. Lenograstim is a G-CSF developed by Chugai and available in some countries as Granocyte.
  • In a 21-day. 200 patient, Chinese trial, treatment with G-CSF improved a 7-category disease severity score by at least 1 point in 12 days vs 13 days with usual care in patients with COVID-19 with lymphopenia but no comorbidities. A small number of patients used interferon (9%), lopinavir/ritonavir (15%) or arbidol (18%) before enrollment.
NIH recommends against the use of ivermectin for the treatment of COVID-19, except in a clinical trial
  • Ivermectin blocks an intracellular process used by viruses to enter cells. The drug has been shown, in vitro, to inhibit SARS-CoV-2 in cell cultures. However, pharmacokinetic/pharmacodynamic studies have shown the levels required to affect replication would require doses 100 times higher than currently approved doses. 
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. The combination of lopinavir and ritonavir inhibits protease, which prevents viral replication and is FDA approved as an HIV treatment. Both drugs are available as generics). Initial case studies and case reports from China, Korea and Singapore suggested activity against COVID-19. 
  • NIH recommends against using lopinavir/ritonavir or other HIV protease inhibitors for the treatment of COVID-19, except as part of a clinical trial.
  • A Chinese trial did not find a benefit with lopinavir and ritonavir, but an editorial questioned if the late start of treatment may have decreased the combination’s activity.
  • The 15,000 patient RECOVERY trial (NCT04381936) has several arms testing lopinavir-ritonavir, dexamethasone, hydroxychloroquine, azithromycin, tocilizumab, convalescent plasma, immunoglobulin (IVIG) and the monoclonal antibody combination REGN-COV2. In the lopinavir-ritonavir arm of the RECOVERY, 1,616 patients that received lopinavir-ritonavir were compared to 3,424 patients that received only usual care. Lopinavir-ritonavir did not improve mortality at 28-days compared to usual care (23% vs 22%), nor did the drugs improve duration of hospital stay, or risk of progressing to invasive mechanical ventilation.
  • The WHO discontinued the lopinavir/ritonavir arm of the Solidarity Trial in July 2020.
  • French researchers prospectively monitored the heart rhythms of 41 hospitalized COVID-19 patients being treated with lopinavir and ritonavir and found that 22% (nine patients) experienced bradycardia at least 48 hours after initiating the drugs.
Molnupiravir (MK-4482) is a ribonucleoside analog that inhibits the replication of multiple RNA viruses including SARS-CoV-2. Molnupiravir is being developed by Merck after licensing the drug from Ridgeback Biotherapeutics. Ridgeback Biotherapeutics began developing molnupiravir while the deal with Merck was begin reviewed.
  • Molnupiravir is an oral drug that is dosed twice a day for 5 days.
  • Ridgeback Biopharmaceuticals called the drug EIDD-2801
    • Ridgeback announced that in a 15-day, 122 patient, Phase I trial (NCT04392219), administration of molnupiravir produced no safety issues at serum levels estimated to reduce pulmonary virus levels.
    • Ridgeback initiated a 28-day, 60 patient Phase II trial (NCT04405739) in June 2020 that is evaluating the effect of molnupiravir on clearing SARS-CoV-2 in hospitalized patients with COVID-19 pneumonia.
    • Ridgeback initiated a 28-day, 44 patient Phase II trial ((NCT04405570) in June 2020 that is evaluating the effect of molnupiravir on clearing SARS-CoV-2 in non-hospitalized patients with COVID-19 pneumonia.
  • Merck took over development of molnupiravir in July 2020 and changed the research code from EIDD-2801 to MK-4482. The drug then was given the generic name, molnupiravir.
    • 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.
Risankizumab (Skyrizi, Boehringer Ingelheim and AbbVie) is a monoclonal antibody approved for the treatment of severe plaque psoriasis.