Pipeline: Investigational Therapies for COVID-19

Updated on 4/29

While no specific treatment for coronavirus disease 2019 (COVID-19) is currently available, several therapies are being investigated globally.*   

Antivirals

Ampligen: AIM ImmunoTech is developing the broad-spectrum antiviral for COVID-19 in Japan. A significant survival effect was observed in a trial evaluating mice infected with the earlier Severe Acute Respiratory Syndrome (SARS) coronavirus. 

Chloroquine, Hydroxychloroquine: The Food and Drug Administration (FDA) has issued a safety alert stating that the use of these agents, either alone or in combination with azithromycin, should be limited to clinical trial settings or for treating COVID-19 patients under the FDA’s Emergency Use Authorization.

Danoprevir: A direct-acting antiviral agent being investigated in combination with ritonavir by Ascletis Pharma to treat COVID-19. Danoprevir is currently approved in China for the treatment of chronic hepatitis C infection.

EIDD-2801: A ribonucleoside analog that inhibits the replication of multiple RNA viruses including SARS-CoV-2. The FDA has approved an Investigational New Drug application (IND) that will allow Ridgeback Biotherapeutics to begin human clinical testing. 

ENU200: An orally delivered antiviral compound previously approved to treat other infections. In-silico modeling conducted by Ennaid has revealed that ENU200 delivers specific antiviral activity against 2 SARS-CoV-2 proteins, S glycoprotein and Mpro. The Company believes it can quickly bring ENU200 to market by treating patients with COVID-19 in a phase 3 in-home, self-dosing clinical trial of patients with asymptomatic, mild to moderate coronavirus infections.

Elsulfavirine: A non-nucleoside reverse transcriptase inhibitor (NNRTI) being investigated by Viriom in a phase 2 trial across Russia and Eastern Europe in adults with moderate manifestations of COVID-19. 

Favipiravir: An antiviral agent approved in Japan for influenza treatment. Fujifilm has announced the initiation of a phase 2 trial in the US. The study will enroll approximately 50 patients with COVID-19, in collaboration with Brigham and Women’s Hospital, Massachusetts General Hospital, and the University of Massachusetts Medical School. 

Galidesivir: An adenosine nucleoside analog that acts to block viral RNA polymerase. BioCryst Pharmaceuticals has opened enrollment into a randomized, double-blind, placebo-controlled trial to assess the safety, clinical impact, and antiviral effects of galidesivir in patients with COVID-19.

Lopinavir/ritonavir: AbbVie is collaborating with select health authorities and institutions to determine the antiviral activity of the HIV drug against COVID-19. Recent trial results published in the New England Journal of Medicine showed that the combination therapy was not associated with clinical improvement in patients with confirmed COVID-19. 

Merimepodib: An orally-administered broad spectrum antiviral being developed by ViralClear Pharmaceuticals. A phase 2 trial will be conducted at Mayo Clinic to evaluate the drug candidate, which targets RNA-dependent polymerases. In vitro data demonstrated decreased viral production of SARS-CoV-2 by over 98%.

Nitazoxanide: An investigational broad spectrum antiviral that has been shown to inhibit replication of SARS, MERS, and other coronaviruses. Romark will initiate two phase 3 clinical trials evaluating nitazoxanide for the prevention of COVID-19 and other viral respiratory illnesses in high-risk populations, including elderly residents of long-term care facilities and healthcare workers.

OT-101: A TGF-β antisense drug candidate that has demonstrated potent antiviral activity against COVID-19. Mateon Therapeutics is expecting to complete the IND submission following submission of a pre-IND application to the FDA to allow the referencing of OT-101’s oncology IND. According to the Company, the mechanism of action for OT-101 against COVID-19 includes inhibition of cellular binding, inhibition of viral replication and suppression of viral induced pneumonia.

Oxypurinol: XORTX Therapeutics is exploring the use of a new formulation of oxypurinol as a novel treatment for acute kidney and lung injury accompanying COVID-19 infection.

Remdesivir: The broad-spectrum antiviral agent, developed by Gilead, is being investigated in a double-blinded, placebo-controlled study sponsored by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health; data is expected by the end of May. In addition, data from an open-label randomized controlled trial involving patients with severe illness is anticipated by the end of April. Results from a trial evaluating patients with moderate illness are expected by May. Leaked data from a small study in China suggested the drug may not be effective, however Gilead stated that the trial was underpowered.

Ribavirin for oral inhalation: Clinical trial initiated in Canada evaluating an investigational use of the nucleoside analog ribavirin for inhalation solution (Virazole; Bausch Health), with standard of care therapy, to treat hospitalized adult patients with respiratory distress due to COVID-19.

Immunotherapies and Other Investigational Therapies

Acalabrutinib:A selective inhibitor of Bruton’s tyrosine kinase (BTK) being investigated by AstraZeneca for the treatment of cytokine storm associated with COVID-19 in severely ill patients. BTK inhibition reduces the production of multiple cytokines and chemokines which may potentially reduce respiratory complications of COVID-19. The Company has initiated an open-label study (CALAVI) to investigate the treatment.

ACE-MAB: Sorrento Therapeutics is developing a bi-specific fusion protein that binds to the spike protein of coronaviruses, which is expected to block SARS-CoV-2 from binding and infecting respiratory epithelial cells or ACE2-expressing cells. 

ATYR1923: A fusion protein composed of the immunomodulatory domain of histidyl tRNA synthetase fused to the FC region of a human antibody. The product, which is being developed by aTyr, will be evaluated in COVID-19 patients with severe respiratory complications. 

Aviptadil (RLF-100): Relief Therapeutics is investigating the vasoactive intestinal polypeptide for the treatment of acute respiratory distress syndrome in patients with COVI-19 infection. The drug has now entered FDA clinical trials at Thomas Jefferson University Hospital. The multicenter trial will enroll patients who are already on mechanical ventilation to see if aviptadil can decrease mortality in this condition.

Baricitinib: Lilly’s oral Janus kinase inhibitor (JAK1/JAK2) is being investigated in an NIH study for the potential treatment of hospitalized patients diagnosed with COVID-19.

Brensocatib: A small molecule, oral, reversible inhibitor of dipeptidyl peptidase I currently being developed by Insmed for the treatment of bronchiectasis and other inflammatory diseases. The drug candidate will be studied in patients with severe COVID-19 in an investigator-initiated trial (STOP-COVID19).

Brilacidin: A defensin-mimetic that mimics the human innate immune system and causes disruption of the membrane of pathogens, leading to cell death. It is being developed by Innovation Pharmaceuticals and has already been tested in humans in phase 2 trials for other indications.

Bucillamine: A cysteine derivative with two thiol groups that has the potential, via restoration of glutathione activity and other anti-inflammatory activity, to lessen the negative consequences of SARS-CoV2 infection in the lungs and to help treat COVID-19 manifestations, according to Revive Therapeutics.

Centhaquine: An investigational resuscitative agent that is expected to provide hemodynamic stability, improve tissue oxygenation, reduce pulmonary edema, reduce acute respiratory distress syndrome, reduce multiple organ dysfunction score and decrease mortality in patients with COVID-19. Pharmazz is approaching various regulatory agencies regarding use of centhaquine as an adjunct in the management of critically ill patients with COVID-19; the drug has already been assessed in a phase 3 study for hypovolemic shock.

Convalescent plasma: Convalescent plasma therapy for COVID-19 is currently being investigated across the nation by more than 1040 sites and 950 physicians through an expanded access program led by the Mayo Clinic. In addition, several clinical trials are evaluating the safety and efficacy of the therapy. The FDA is also accepting single-patient emergency Investigational New Drug Applications for individual patients.Recovered patients are being urged to donate plasma.

Dapagliflozin: A phase 3 trial evaluating the sodium-glucose cotransporter 2 (SGLT2) inhibitor as a potential treatment for patients hospitalized with COVID-19 who are at risk of developing serious complications, has been initiated by AstraZeneca and Saint Luke’s Mid America Heart Institute.

DAS181: A recombinant sialidase protein that cleaves sialic acid located on the surface of epithelial cells lining the human respiratory tract. Ansum Biopharma is enrolling patients in a proof-of-concept study to evaluate the safety and efficacy of the investigational agent for severe COVID-19 infection.

gammaCore: electroCore has submitted an Emergency Use Authorization application to the FDA to facilitate the study and clinical use of its gammaCore Sapphire^TM non-invasive vagus nerve stimulation therapy for respiratory symptoms associated with COVID-19. The hand-held therapy, which is applied at the neck, is currently approved for treating migraine and cluster headache.

CD24Fc: A first-in-class biologic that fortifies an innate immune checkpoint against excessive inflammation caused by tissue injuries. OncoImmune, Inc. has received approval from the FDA for its phase 3 clinical trial evaluating the safety and efficacy of CD24Fc for the treatment of hospitalized COVID-19 patients. A cohort of 230 patients with severe clinical symptoms will be randomized and administered a single dose of CD24Fc or placebo and followed for a 14-day period.

CM4620-IE: A potent and selective small molecule inhibitor of calcium release-activated calcium (CRAC) channels. According to CalciMedica, the investigational agent may prevent pulmonary endothelial damage and lessen the cytokine storm in COVID-19. A phase 2 trial is underway and is expected to enroll 60 patients with severe COVID-19 pneumonia.

Famotidine: The H2 blocker is being investigated at Northwell Health in New York City following reports from China suggesting that the drug could potentially improve clinical outcomes in COVID-19 patients.  

Gimsilumab: A fully human monoclonal antibody targeting granulocyte-macrophage colony stimulating factor (GM-CSF) being developed by Roivant Sciences to treat acute respiratory distress syndrome associated with COVID-19. Gimsilumab has demonstrated a favorable safety and tolerability profile based on data collected to date.

HB-adMSC: The FDA has approved a phase 2 trial evaluating the efficacy and safety of Hope Biosciences’ autologous, adipose-derived mesenchymal stem cells (HB-adMSCs) to provide immune support against COVID-19. The study is expected to enroll 75 patients that are either over 50 years of age, have preexisting health conditions, or are at high-exposure risk.

Ifenprodil: An N-methyl-D-aspartate (NDMA) receptor glutamate receptor antagonist being developed by Algernon Pharmaceuticals. The Company is preparing for US trials based on results of an animal study that showed the investigational therapy significantly reduced acute lung injury and improved survivability in H5N1 infected mice.

Inhaled nitric oxide: The FDA has granted emergency expanded access for use of the INOpulse® system (Bellerophon Therapeutics) and the Genosyl DS tankless system (VERO Biotech) for treatment of COVID-19. In a clinical study of patients infected with SARS-CoV, nitric oxide demonstrated improvements in arterial oxygenation.

Ivermectin: An FDA-approved anti-parasitic agent that has shown antiviral activity against SARS-CoV-2 in vitro. MedinCell has launched a research initiative on a long-acting injectable formulation of ivermectin for COVID-19.

LB1148: A broad spectrum serine protease inhibitor designed to neutralize the activity of digestive proteases and preserve gut integrity during intestinal distress (eg, shock, infections, surgery). Leading BioSciences believes its mechanism of action may limit the viral load in patients with COVID-19 as the SARS-CoV-2 virus uses the ACE2 receptor, which is highly expressed in the lung and GI tract to infect epithelial cells of these organs.

LEAPS peptides: CEL-SCI is developing an immunotherapy using a patented T cell modulation peptide epitope delivery technology, to stimulate protective cell-mediated T cell responses and reduce viral load.

LY3127804: An investigational selective monoclonal antibody against angiopoietin 2 (Ang2) being developed by Lilly for pneumonia patients hospitalized with COVID-19 who are at high risk of progressing to acute respiratory distress syndrome. A phase 2 trial is expected to begin in late April.

Mavrilimumab: Kiniksa is investigating a fully-human monoclonal antibody designed to antagonize granulocyte macrophage colony stimulating factor (GM-CSF) signaling by binding to the alpha subunit of the GM-CSF receptor (GM-CSFRα). In a prospective, interventional, single-active-arm, single-center pilot study, patients with severe pulmonary involvement of COVID-19, acute respiratory distress, fever, and clinical and biological markers of systemic hyperinflammation status​ were treated with a single intravenous dose of mavrilimumab. To date, 6 patients have been treated; patients showed early resolution of fever and improvement in oxygenation within 1-3 days.

Multi-antibody cocktail therapy: Regeneron is developing a novel therapy that could potentially be administered as prophylaxis before exposure to SARS-CoV-2 virus or as a treatment for those already infected. It may potentially enter human trials by early summer.

MultiStem therapy: Athersys will initiate a phase 2/3 study to assess the safety and efficacy of its stem cell product candidate for the treatment of acute respiratory distress syndrome induced by COVID-19. First clinical sites for the MultiStem Administration for COVID-19 Induced ARDS (MACOVIA) study are expected to open in the second quarter of 2020.

Pacritinib: An investigational oral kinase inhibitor with specificity for JAK2, IRAK1 and CSF1R. CTI BioPharma will evaluate the potential of pacritinib in preventing the development of an inflammatory response to COVID-19 in the phase 3 PRE-VENT study. 

Remestemcel-L: Mesoblast Limited is investigating its allogeneic mesenchymal stem cell (MSC) product candidate, as a treatment for patients with acute respiratory distress syndrome caused by COVID-19. Remestemcel-L, which is composed of culture-expanded MSCs derived from the bone marrow of an unrelated donor, is administered in a series of intravenous infusions and is believed to have immunomodulatory properties to counteract inflammatory processes. A randomized, placebo-controlled trial is being conducted at Mount Sinai hospital in New York City.

Ruxolitinib: Incyte is initiating a phase 3 study evaluating the efficacy and safety of ruxolitinib, a Janus kinase inhibitor, in patients with COVID-19 associated cytokine storm. The Company intends to launch an Expanded Access Program to allow eligible patients to receive ruxolitinib, which is marketed under the brand name Jakafi in the US, while it is being investigated for COVID-19. 

Sargramostim: A yeast-derived recombinant humanized granulocyte-macrophage colony stimulating factor (rhuGM-CSF) being assessed in the SARPAC trial (sargramostim in patients with acute hypoxic respiratory failure due to COVID-19) at University Hospital Ghent to treat patients with respiratory illness associated with COVID-19. Sargramostim is marketed under the brand name Leukine (Partner Therapeutics) in the US.

Sarilumab: Regeneron and Sanofi are evaluating the interleukin-6 (IL-6) receptor antagonist in patients hospitalized with severe COVID-19 infection. The first part of the trial will evaluate the impact of sarilumab on fever and patient’s need for supplemental oxygen, while the second part will evaluate improvement in longer-term outcomes (ie, preventing death, reducing need for mechanical ventilation, supplemental oxygen and/or hospitalization).

Siltuximab: A study has been initiated at the Papa Giovanni XXIII Hospital, Bergamo Italy, to investigate the use of the interleukin (IL)-6 targeted monoclonal antibody for the treatment of patients with COVID-19 who have developed serious respiratory complications (Siltuximab In Serious COVID-19; SISCO study). Interim data from the first 21 patients show that 7 patients experienced clinical improvement with a reduced need for oxygen support and 9 patients had no clinically relevant changes; worsening was seen in 3 patients and 1 patient died. In the US, siltuximab (Sylvant; EUSA Pharma) is currently approved for multicentric Castleman disease in adults who are HIV negative and human herpesvirus-8 (HHV-8) negative.

ST266: A cell-free platform biologic containing hundreds of anti-inflammatory proteins. According to Noveome Biotherapeutics, its lead product candidate has the potential to treat severe inflammatory cytokine storm observed in COVID-19 patients. Human clinical trials are expected by the fourth quarter 2020.

Tocilizumab: Genentech is initiating a randomized, double-blind, placebo-controlled phase 3 trial in collaboration with the Biomedical Advanced Research and Development Authority (BARDA) to evaluate the safety and efficacy of the IL-6 receptor antagonist plus standard of care in hospitalized adult patients with severe COVID-19 pneumonia.

TAK-888: An anti-SARS-CoV-2 polyclonal hyperimmune globulin (H-IG) being developed by Takeda for high-risk individuals with COVID-19. Pathogen-specific antibodies from plasma will be collected from recovered patients (or vaccinated donors in the future) and will be transferred to sick patients to improve the immune response to the infection and increase the chance of recovery.

Tradipitant: A neurokinin-1 receptor antagonist being evaluated by Vanda Pharmaceuticals for the treatment and prevention of pneumonia associated with COVID-19. The phase 3 ODYSSEY study will include 300 patients with severe infection.

TD-0903: A lung-selective nebulized Janus kinase inhibitor in clinical development to assess its utility in preventing the cytokine storm associated with acute lung injury in patients hospitalized due to COVID-19, with the ultimate goal of preventing progression to acute respiratory distress syndrome. According to Theravance Biopharma, a phase 1 study is expected to begin soon in the UK.

TZLS-501: The investigational therapy, being developed by Tiziana, has been shown to rapidly deplete circulating levels of IL-6 in the blood, a key driver of chronic inflammation. Excessive production of IL-6 is believed to be associated with severe lung damage observed with COVID-19 infections.

Vazegepant: An intranasal, high-affinity calcitonin gene-related peptide receptor antagonist that will be evaluated in the treatment of pulmonary complications of COVID-19. Biohaven Pharmaceuticals announced that the FDA has approved a phase 2 study.

Vaccines

Altimmune Inc: Developing a single-dose, intranasal vaccine against COVID-19 using its proprietary NasoVAX technology. The vaccine is moving toward animal testing.

Applied DNA Sciences: Collaborating with Takis Biotech to develop a DNA vaccine candidate using PCR-based DNA (“LinearDNA”) manufacturing systems; preclinical testing in animals is expected to begin in the second quarter of 2020.

Codagenix Inc: Co-developing a live-attenuated vaccine with the Serum Institute of India using viral deoptimization.

GlaxoSmithKline: Collaborating with Clover Biopharmaceuticals to develop a protein-based coronavirus vaccine candidate (COVID-19 S-Trimer) using Clover’s proprietary technology (Timer-Tag©) and combining it with GSK’s pandemic adjuvant system.

Inovio Pharmaceuticals: Developing a DNA vaccine (INO-4800) to address COVID-19; human trials to begin in the US in April.

Johnson & Johnson: Partnering with the Biomedical Advanced Research and Development Authority (BARDA) to develop a vaccine using Janssen’s AdVac® and PER.C6® technology, which provide the ability to rapidly upscale production of an optimal vaccine candidate.

Moderna Inc: Vials of the Company’s mRNA vaccine (mRNA-1273) have been shipped to the National Institute of Allergy and Infectious Diseases to be used in a phase 1 study in the US. The Company is actively preparing for a potential phase 2 trial based on the outcomes of the NIH study.

Novavax: Currently evaluating multiple recombinant nanoparticle vaccine candidates in animal models; initiation of phase 1 testing is expected in late spring of 2020. The COVID-19 vaccine candidates will likely include the saponin-based Matrix-M™ adjuvant to enhance immune responses.

Pfizer and BioNTech: Co-developing a potential first-in-class COVID-19 mRNA-based vaccine candidate (BNT162), which is expected to enter clinical testing by the end of April 2020. 

Sanofi: Collaborating with BARDA to develop a vaccine using Sanofi’s recombinant DNA platform. The DNA sequence encoding the antigen will be combined into the DNA of the baculovirus expression platform and used to produce large quantities of the coronavirus antigen which will be formulated to stimulate the immune system to protect against the virus.

Sanofi and GlaxoSmithKline: The Companies are collaborating on an adjuvanted vaccine using Sanofi’s S-protein COVID-19 antigen and GSK’s pandemic adjuvant technology. A candidate vaccine is expected to enter clinical trials in the second half of 2020, and if successful, may be available by the second half of 2021.

Sorrento Therapeutics: Developing STI-6991, an I-Cell^TM COVID-19 cellular vaccine made of replication-deficient human erythroleukemia K562 cells expressing membrane-bound S1 protein of the SARS-CoV-2 virus. The I-Cell vaccine is expected to elicit both T cell and B cell immunities against SARS-CoV-2.

*Not an inclusive list. Updates will be made as more information becomes available.