COVID-19 Antivirals 2023

COVID-19 Antivirals August 2023

There are approved treatments that may help reduce how sick people become when diagnosed with COVID‑19. If you test positive for COVID‑19, you may be eligible for antiviral therapies, including oral or intravenous antivirals, says the U.S. Health and Human Services (HHS). The U.S. NIH COVID-19 Treatment Guidelines were recently updated for Adults, Children, Pregnancy, and Lactation. The European Medicines Agency (EMA) human medicines committee separately evaluates COVID-19 antiviral therapies. And the World Health Organization (WHO) has Listed antiviral products.

U.S. FDA COVID-19 Antivirals

The U.S. Food and Drug Administration (FDA) issued Emergency Use Authorizations (EUA) and Approvals for the antiviral agents Paxlovid™, Lagevrio, Veklury®, and Actemra®. As of August 2023, the U.S. Centers for Disease Control and Prevention (CDC) recommends their use for people infected by the SARS-CoV-2 coronavirus and impacted by COVID-19. The U.S. CDC Clinician Outreach and Communication Activity webinar on January 24, 2023, presented 'Updates to COVID-19 Testing and Treatment for the Current SARS-CoV-2 Variants.'

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. The FDA issued approval on May 25, 2023.

Lagevrio™ (Molnupiravir) is the oral prodrug of beta-D-N4-hydroxycytidine, a ribonucleoside with broad antiviral activity against RNA viruses. The FDA issued a revised EUA #108 on February 1, 2023.

Veklury® (remdesivir; GS-5734, DESREM, Redyx) is a nucleotide analog with broad-spectrum antiviral activity.

Actemra® (tocilizumab) is approved for intravenous treatment of COVID-19 in hospitalized adult patients receiving systemic corticosteroids and requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation. As of January 2023,  Actemra / RoActemra is approved in the European Union, Japan, the United Kingdom, and the U.S.

China COVID-19 Antivirals 2023

Sorrento Therapeutics STI-1558 is a prodrug, and its active form AC1115 binds to Cys-145 of the catalytic domain of Mpro, which is 100% conserved in all SARS-CoV-2 variants and achieves a broad-spectrum anti-SARS-CoV-2 activity, including against the original SARS-CoV-2 strain as well as the predominant variants of concern (VOCs), such as Delta and Omicron. STI-1558 is also a Cathepsin L inhibitor, which may block effective viral entry into host cells without accelerating viral mutations. As of June 26, 2023, should the Phase 3 trial be successful, the Company plans to open dialogue with regulatory agencworldwideorld to discuss paths to approval.

Shanghai Junshi Biosciences Co., Ltd announced on January 29, 2023, the National Medical Products Administration approved under Special Examination and Approval of Drugs, conditionally authorized the marketing of Deuremidevir Hydrobromide Tablets (JT001/VV116, "VV116"), an oral nucleoside analog anti-SARS-CoV-2 drug, for the treatment of adult patients with mild to moderate COVID-19. On December 28, 2022, the NEJM published an Original Article: VV116 versus Nirmatrelvir–Ritonavir for Oral Treatment of Covid-19 - Conclusion: Among adults with mild-to-moderate Covid-19 who were at risk for progression, VV116 was noninferior to nirmatrelvir–Ritonavir concerning the time to sustained clinical recovery, with fewer safety concerns, in a phase 3 study.

Hong Kong-listed Simcere Pharmaceutical Group began marketing XIANNUOXIN on January 31, 2023. XIANNUOXIN is a combination packaged drug of a small molecule anti-SARS-CoV-2 drug candidate and Ritonavir, this candidate targets the 3CL protease, which is essential for SARS-CoV-2 viral replication.

Japan COVID-19 Antivirals

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. 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. In addition, on February 15, 2023, the U.S. NIH confirmed it would launch a phase 3 study, and on April 4, 2023, the FDA granted Fast Track Designation. On June 9, 2023, Shionogi announced the first participant had been enrolled in Japan in its global Phase 3 study, Stopping COVID-19 pRogression with Early Protease InhibitOr Treatment – Post Exposure Prophylaxis (SCORPIO-PEP). In addition, Shionogi also announced that it has filed for full approval of ensitrelvir in Japan.

Antivirals Repurposed to Treat COVID-19

The Lancet Infectious Diseases published results from a study on June 8, 2023, Outpatient treatment of COVID-19 and incidence of post-COVID-19 condition over ten months (COVID-OUT): a multicentre, randomized, quadruple-blind, parallel-group, phase 3 trial - that a two-week course of metformin given within three days of coronavirus infection led to 40% fewer long covid diagnoses over the following ten months. A non-peer-reviewed study published on December 22, 2022, reaffirmed findings from an ORIGINAL ARTICLE published by the NEJM on August 18, 2022, the decrease in viral load among participants treated with the U.S. FDA-approved drug Metformin was 4.4-fold more significant vs. placebo in phase 3 clinical trial.

The JAMA Network reported on December 15, 2022, that among critically ill patients with COVID-19 who receive one 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 July 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 February 12, 2022 - results suggest that the addition of inhaled Budesonide to routine care is safe and showed a reduction in disease progression. 

BMS's ORENCIA® (abatacept) is indicated and U.S. FDA-approved for treating 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 ACE2 protein on the cell surface regulates the protein that the SARS-CoV-2 coronavirus uses as a gateway for infection.

COVID-19 Treatment Candidates 2023

NanoViricides, Inc. reported that the Phase 1a/1b Human Clinical Trial of NV-CoV-2, a broad-spectrum antiviral drug, is progressing successfully. The Company reported on August 21, 2023, that its Indian collaborator and drug sponsor, Karveer Meditech Pvt. Ltd., India, has communicated that approximately 26 out of the target of 36 healthy volunteers in the various cohorts in the Phase 1a Single-Ascending-Dose have already completed the study.

RedHill Biopharma's (RHB-107, ABC294640), 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. RHB-107 (upamostat) was accepted for inclusion in ACESO's PROTECT adaptive platform trial for early COVID-19 outpatient treatment in the U.S., Thailand, Ivory Coast, and South Africa.

Atea Pharmaceuticals, Inc. is evaluating bemnifosbuvir (AT-527) for ttreatingCOVID-19 in non-hospitalized patients. Bemnifosbuvir is a nucleotide polymerase inhibitor that targets the SARS-CoV-2 RNA polymerase (nsp12). Bemnifosbuvir was granted FDA Fast Track status on April 25, 2023.

Gilead Sciences phase 3 clinical study tests how Obeldesivir (GS-5245) works and is safe in treating COVID-19 patients. On April 16, 2023, results demonstrated that obeldesivir reached expected therapeutic plasma concentrations for treating COVID-19. Therefore, Gilead has advanced obeldesivir into two Phase 3 studies – BIRCH and OAKTREE – to assess the efficacy and safety of obeldesivir for the treatment of non-hospitalized participants with COVID-19.

Pfizer Inc. and Clear Creek Bio, Inc. announced a research collaboration and exclusive license agreement to advance the discovery and development of potential inRS-CoV-2 papain-like protease (PLpro) inhibitors r the oral treatment of COVID-19. PLpro is an essential enzyme, along with the main protease, and is necessary for 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 Company is developing sabizabulin 9mg, a novel oral microtubule disruptor, which has both host-targeted antiviral and broad anti-inflammatory properties, as a two-pronged approach to the treatment of hospitalized patients with viral lung infection at high risk for ARDS and death. The FDA informed the Company on March 2, 2023, that it declined to grant the request for EUA for sabizabulin. Health Canada accepted for review of Veru's New Drug Submission for sabizabulin for COVID-19 on January 26, 2023.

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.

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 preventing and treating COVID-19, including disease caused by most variants, as 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.

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 8eighttimes per day. Tests concluded that ProLectin-M binds relatively strongly to galectin-3 with micromolar affinity down to 2µM. In addition, while the Galectin Antagonist indeed binds to the S1 Spike Protein, the study showed that it could bind in 2 different orientations with galectin-3.

Kinarus Therapeutics Holding AG announced on December 6, 2022, new preclinical data showing KIN001's 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 are actively recruiting.

BiondVax Pharmaceuticals Ltd. inhaled NanoAb COVID-19 prophylactic and therapeutic drug; Previously announced data indicated NanoAb treatment one-day post-infection led to significantly milder illness, faster recovery, and lower viral lung titer in comparison to the placebo group. In 2023, BiondVax is expected to conduct a preclinical toxicity study to assess safety as regulatory authorities require approval of human clinical trials. 

BIOXYTRAN, INC. announced on August 8, 2023, based on the success of Bioxytran's Phase 2 trial in mild to moderate COVID-19 patients, which achieved a 100% response rate by day seven versus 6% in placebo, in the Central Drugs Standard Control Organization in India approved the clinical trial protocol. The Company is initiating the first stage of its registrational trial,l, an Oral ProLectin-M dose optimization study that will evaluatethree3 different dosage levels against a matching placebo arm in a 5-day trial.

60 Degrees Pharmaceuticals announced on April 26, 2023, that the United States Patent and Trademark Office had issued a patent covering the use of tafenoquine as a treatment for COVID-19 disease. Tafenoquine is the active molecule in the Company's FDA-approved regimen for malaria prevention, ARAKODA®. This product is not FDA-approved for treating COVID-19.