COVID-19 Antivirals

COVID-19 Antiviral Treatments - U.S. FDA Authorized

The U.S. Food and Drug Administration (FDA) issued Emergency Use Authorizations (EUA) and Approvals for the antiviral agents Paxlovid™, Molnupiravir, Veklury, and Actemra®. And as of December 5, 2022, the U.S. Centers for Disease Control and Prevention (CDC) recommends their use for people impacted by COVID-19.

Paxlovid™ - Nirmatrelvir plus PF-07321332 is an orally bioavailable protease inhibitor active against mPRO, a viral protease that plays an essential role in viral replication by cleaving the two viral polyproteins. Paxlovid is authorized in the U.S. for certain adults and children and in Europe and the U.K. for adults. In addition, on July 6, 2022, the FDA authorized certain pharmacists to prescribe Paxlovid in the U.S. A recent U.S. NIH-funded Original Investigation concluded Paxlovid reduced hospitalization or death risk.

Lagevrio (Molnupiravir) is the oral prodrug of beta-D-N4-hydroxycytidine, a ribonucleoside with broad antiviral activity against RNA viruses. However, NHC uptake by viral RNA-dependent RNA-polymerases can result in viral mutations and lethal mutagenesis. Therefore, the WHO's ninth update included a conditional recommendation for the treatment with molnupiravir for those at the highest risk of hospitalization on March 3, 2022.

Veklury (remdesivir; GS-5734, DESREM, Redyx) is a nucleotide analog with broad-spectrum antiviral activity. On April 25, 2022, the U.S. FDA expanded the approval of Veklury to include certain pediatric patients 28 days of age and older weighing at least 3 kilograms.

Actemra® (tocilizumab) is approved for intravenous treatment of COVID-19 in hospitalized adult patients who are receiving systemic corticosteroids and require supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation.

To improve access to Covid-19 treatments, the U.S. administration recently launched the "Test to Treat" initiative with local pharmacies.

COVID-19 Antivirals Approved Internationally

The European Medicines Agency (EMA) has authorized various therapies for use in Europe. And the World Health Organization (WHO) has Listed (19) products.

Japan Approved COVID-19 Antiviral

Shionogi & Co., Ltd. announced on November 22, 2022, that Xocova® (ensitrelvir fumaric acid, Code No.: S-217622) obtained emergency regulatory approval from the Ministry of Health, Labour and Welfare (MHLW) in Japan for the indication of SARS-CoV-2 infection. Xocova is an oral antiviral agent administered once daily for five days that suppresses the replication of the SARS-CoV-2 coronavirus by selectively inhibiting the viral 3CL protease.

Shionogi announced it entered into an additional purchasing contract of 1 million courses of Xocova® tablets (ensitrelvir fumaric acid) with Japan's MHLW on December 12, 2022.

COVID-19 IV Infusion - Approved

Actemra / RoActemra (tocilizumab) is a first-in-class anti-interleukin-6 receptor intravenous (IV) therapy for treating rheumatoid arthritis, systemic juvenile idiopathic arthritis, polyarticular juvenile idiopathic arthritis, giant cell arteritis, and chimeric antigen receptor T-cell induced severe or life-threatening cytokine release syndrome. On December 7, 2021, the European Commission approved its use for certain COVID-19 patients in Europe, As of December 2022, Actemra / RoActemra is approved for defined patients hospitalized with severe or critical COVID-19 in multiple territories, including the European Union, Ecuador, Honduras, Japan, Myanmar, Peru, and the United Kingdom, provisionally approved in Australia, and authorized for emergency use in Ghana and the U.S. The WHO has also recommended it.

Medications Repurposed to Treat COVID-19

The JAMA Network reported on December 15, 2022, that among critically ill patients with COVID-19 who receive 1 or more therapeutic interventions, treatment with an IL-6 receptor antagonist had a greater than 99.9% probability of improved 180-day mortality, according to the latest data from the REMAP-CAP clinical trial.

Genuine Biotech's Azvudine (FNC) is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase (RdRp). FNC monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC50 between 1.2 and 4.3 μM, depending on viruses or cells, and selective index in the 15-83 range. Azvudine was authorized for use against COVID-19 in China on July 25, 2022.

Eli Lilly's Olumiant (Baricitinib) is a Janus kinase inhibitor. Its active substance, baricitinib, blocks the action of enzymes that play an essential role in immune processes that lead to inflammation. Olumiant was authorized by the FDA on Jul. 28, 2021, to treat certain COVID-19 in hospitalized adults and pediatric patients. And then FDA Approved it on May 11, 2022. On March 3, 2022, the WHO strongly recommended the treatment with baricitinib. It is available in about 75 countries to treat adults with moderate to severe rheumatoid arthritis.

Fluvoxamine is a selective serotonin reuptake inhibitor approved by the U.S. FDA for treating obsessive-compulsive disorder.

Inhaled Budesonide treats Crohn's disease and is in a class of medications called corticosteroids. An investigator-initiated, open-label, randomized clinical trial explored the efficacy of adding inhaled Budesonide to usual care to prevent disease progression in patients hospitalized with COVID-19 pneumonia on Feb. 12, 2022 - results suggest that the addition of inhaled Budesonide to usual care is safe and showed a reduction in disease progression.

BMS's ORENCIA® (abatacept) is indicated and U.S. FDA-approved for the treatment of adult patients with moderately to severely active rheumatoid arthritis. ORENCIA is a selective costimulation modulator that disrupts the continuous cycle of T-cell activation. People in the Orencia group had 34.2% better odds of clinical improvement than those in the placebo group.

Kineret is a prescription medicine approved in Europe and the U.S. to treat signs and symptoms of rheumatoid arthritis in adults and those with a Deficiency of Interleukin-1 Receptor Antagonist. The EMA authorized (EMEA/H/C/000363) Kineret's use for certain COVID-19 patients in December 2022. Kineret contains the active substance anakinra.

VIRALEX (Inosine pranobex) 500 mg tablet is an immunomodulatory agent with broad-spectrum antiviral properties authorized in India and the U.K. It enhances both innate & adaptive immunity and strengthens the body's defense response to viral infections. A recent phase 3 study initiated by Themis Medicare found that 80.17% of patients treated with VIRALEX showed clinical improvement on day 6.

Icatibant is sold by Takeda Pharmaceutical Co as Firazyr blocks a protein called bradykinin receptor b2 in the kinin system. The protein is regulated by the ACE2 protein on the cell surface that the SARS-CoV-2 coronavirus uses as a gateway for infection.

COVID-19 Treatment Candidates - 2022

Pfizer Inc. and Clear Creek Bio, Inc. announced a research collaboration and exclusive license agreement to advance the discovery and development of potential inhibitors of the SARS-CoV-2 papain-like protease (PLpro) for the oral treatment of COVID-19. PLpro is an essential enzymh, along with the main protease, and plays an important role in viral replication.

Veru Inc. Sabizabulin is a novel dual antiviral and anti-inflammatory agent for treating hospitalized moderate-severe COVID-19 patients at high risk for ARDS and death. The FDA informed the Company that FDA's Pulmonary-Allergy Drugs Advisory Committee would meet on November 9, 2022, to discuss the Company's sabizabulin for COVID-19 request for emergency use authorization.

SaNOtize's Nitric Oxide Nasal Spray represents a safe and effective antiviral treatment that shortens the course of COVID-19 and could prevent the transmission of COVID-19; it is approved in Singapore, Malaysia, Taiwan, India, and Israel.

Brilacidin (PMX-30063) is a synthetic, non-peptidic small molecule that kills pathogens swiftly, significantly reducing drug resistance development. As a result, Brilacidin has been granted U.S. FDA Fast Track designation.

NRx Pharmaceuticals's ZYESAMI® (Aviptadil) targets patients with COVID-19 respiratory failure and is available in the U.S. under the Federal Right to Try Law.

RedHill Biopharma's (RHB-107, ABC294640) Opaganib, a first-in-class new chemical entity, is a sphingosine kinase-2 (SK2) selective inhibitor in oral pill form with dual anti-inflammatory and antiviral activity.

Molecular Partners AG's Ensovibep is a DARPin therapeutic candidate explicitly designed to inhibit target cell entry of SARS-CoV-2. DARPins (Designed Ankyrin Repeat Proteins) are mono or multi-specific protein-based therapies that engage their targets for various effects.

Enanta Pharmaceuticals's EDP-235 is a coronavirus 3CL protease inhibitor designed explicitly as a once-daily oral treatment for COVID-19. It is in a first-in-human Phase 1 study and recently was granted FDA Fast Track Designation.

Adagio Therapeutic's Adintrevimab (ADG20) is a potent, broadly neutralizing antibody for the prevention and treatment of COVID-19, including disease caused by most variants, as either a single or combination agent, in phase 2/3 studies.

Sorrento Therapeutics Abivertinib is a novel dual-target, small molecule tyrosine kinase inhibitor designed to selectively target mutant forms of the epidermal growth factor receptor and Bruton's tyrosine kinase, a third-generation EGFR inhibitor. The FDA issued clearance for a Phase 2/3 Study for Abivertinib in the Treatment of Hospitalized Patients With Severe Pneumonia Due to COVID-19.

Sorrento Therapeutics STI-1558 is a potent Mpro inhibitor with an IC50 value of 2.7 nM and has demonstrated potent antiviral activity against all COVID-19 variants studied, including Omicron, with an IC90 value between 14 nM and 41 nM (an IC50/IC90 is the concentration of drug need to produce a 50%/90% inhibition of activity) in vitro following infection of human bronchial epithelial cells. It is also a Cathepsin L inhibitor, which may block effective viral entry into host cells. Sorrento expects the human efficacious dose to be between 300 mg and 600 mg BID without needing a Ritonavir boost.

Kintor Pharmaceutical's Proxalutamide is an ACE2 and TMPRSS2 (transmembrane protease, serine 2) proteins inhibitor that inhibits the entry of the SARS-CoV-2 coronavirus into host cells, conducting phase 3 clinical research.

Sen-Jam Pharmaceutical's investigational therapeutic SJP-002C for the treatment of COVID-19 is actively enrolling clinical trial participants under a co-development agreement with Duke-NUS and Duke University School of Medicine.

Synairgen plc's SNG001 is a pH-neutral formulation of interferon-beta (IFN-beta) for inhalation that is delivered directly into the lungs using a mesh nebulizer, currently being investigated as a potential host-directed antiviral treatment for patients hospitalized with COVID-19, and due to viral infections such as influenza, Respiratory Syncytial Virus, and para-influenza.

ASC10 is an oral double prodrug with a new and differentiated chemical structure from the single prodrug molnupiravir. After oral administration, ASC10 and molnupiravir are rapidly and completely converted in vivo into the same active metabolite ASC10-A, also known as β-D-N4-hydroxycytidine.

eFFECTOR Therapeutics, Inc. announced it had completed enrollment for the second cohort of a three-cohort Phase 1b clinical trial of zotatifin in non-hospitalized adults with confirmed COVID-19 infection. eFFECTOR expects to report topline data for all three cohorts in the first half of 2023.

BioXytran Inc. orally administered Galectin Antagonist in the form of a chewable tablet was administered 8 times per day. Tests concluded that ProLectin-M binds relatively strongly to galectin-3 with micromolar affinity down to 2µM. While the Galectin Antagonist does indeed bind to the S1 Spike Protein, the study showed that it could bind in 2 different orientations with galectin-3.

Atea Pharmaceuticals, Inc. is evaluating bemnifosbuvir (AT-527) for the treatment of COVID-19 in non-hospitalized patients. Bemnifosbuvir is a nucleotide polymerase inhibitor that targets the SARS-CoV-2 RNA polymerase (nsp12), a highly conserved gene that is unlikely to change as the virus mutates and new variants continue to emerge.

Kinarus Therapeutics Holding AG announced on December 6, 2022, new preclinical data showing KIN001 strong antiviral efficacy against the SARS-CoV-2 Omicron subvariants BA.2 and BA.5. The KINFAST Phase 2 trial of KIN001 in ambulatory COVID-19 patients is actively recruiting.