Coronavirus treatment: These are the drugs that show promising results in treating COVID-19 patients
Coronavirus has claimed at least 10,447 lives with a total of 254,701 confirmed cases worldwide. A total of 89,071 people have recovered from the virus. The outbreak has led to panic and pandemonium. As we reported yesterday, there are only three major types of treatments: antiviral drug, antibody solution (including blood plasma) and vaccine.
Even though the need to develop new vaccines seems to be getting a lot of headlines, vaccine, however, does not provide the immediate relief for people who are already infected with the virus. In addition, experts are saying that it may take between 12 to 24 months before the vaccine becomes available. Some are going as far as saying it could be 2022 before we see a COVID-19 vaccine.
In the meantime, more companies are coming out with existing antiviral and experimental drugs that have proven to show promising results in treating COVID-19 patients. While there are no FDA-approved therapeutics or drugs to treat, cure or prevent COVID-19, there are several FDA-approved treatments that may help ease the symptoms from a supportive care perspective.
Below is a list of existing and experimental drugs that are currently being used by doctors and hospitals here in the United States and countries around the world.
Chloroquine – Yesterday, the FDA approved compassionate use of anti-malaria drug chloroquine for the treatment of coronavirus. U.S. President Donald Trump also announced yesterday that chloroquine (hydroxychloroquine/Plaquenil), a drug used to treat malaria and arthritis, has been approved by the US Food and Drug Administration (FDA) to be tested as a treatment for COVID-19. Chloroquine is being tested in various clinical trials conducted by government agencies and academic institutions. FDA also said: “We have been working closely with other government agencies and academic centers that are investigating the use of the drug chloroquine, which is already approved for treating malaria, lupus and rheumatoid arthritis, to determine whether it can be used to treat patients with mild-to-moderate COVID-19 to potentially reduce the duration of symptoms, as well as viral shedding, which can help prevent the spread of disease.” Yesterday, Biopharma giant Bayer announced it is donating 3 million tablets of malaria medicine chloroquine, a 70-year old anti-malaria drug that’s available for cheap.
Remdesivir: Health officials from WHO said that remdesivir, a drug manufactured by Gilead, has demonstrated efficacy in treating the coronavirus infection. According to a report from the FDA, last month, the National Institutes of Health (NIH) began a randomized controlled trial for the treatment of COVID-19 patients with the investigational antiviral drug remdesivir. The FDA has been working with the drug sponsor, Gilead Sciences Inc., to find multiple pathways to both study the drug under the FDA’s investigational new drug requirements, and thus collect helpful data about the efficacy of the drug, as well as provide the drug to patients under emergency use. “To date, the agency has already granted about 250 patients access to this product. The data collected from the expanded access program may contribute to the agency’s understanding of the drug, but controlled clinical trials are needed to determine if it safe and effective for the treatment of COVID-19 infection,” FDA said.
Favilavir: The National Medical Products Administration of China approved the use of Favilavir, an anti-viral drug, as a treatment for coronavirus. The drug has reportedly shown efficacy in treating the disease with minimal side effects in a clinical trial involving 70 patients. The clinical trial is being conducted in Shenzhen, Guangdong province.
Hydroxychloroquine: A new study conducted by renowned research professor Didier Raoult M.D/Ph.D, et. al in Marseille, France, showed that 100% of patients that received a combination of Hydroxychloroquine (HCQ) and Azithromycin tested negative and were virologically cured within 6 days of treatment. The combination of these two drugs were shown to be more effective than for patients treated with just Chloroquine.
HIV drugs for coronavirus treatment: Abbvie’s HIV protease inhibitor, lopinavir is being studied along with ritonavir for the treatment of MERS and SARS coronaviruses. The repurposed drug is already approved for the treatment of HIV infection under the trade name Kaletra®. The combination is listed in the WHO list of essential medicines. Lopinavir is believed to act on the intracellular processes of coronavirus replication and demonstrated reduced mortality in the non-human primates (NHP) model of the MERS. Lopinavir/ritonavir in combination with ribavirin showed reduced fatality rate and milder disease course during an open clinical trial in patients in the 2003 SARS outbreak.
Cipla is also reportedly planning to repurpose its HIV drug LOPIMUNE, which is a combination of protease inhibitors Lopinavir and Ritonavir, for the treatment of coronavirus. A licensed generic of Kaletra®, LOPIMUNE is currently available in packs of 60 tablets each, containing 200mg of Lopinavir and 50mg of Ritonavir. Janssen Pharmaceutical Companies, a subsidiary of Johnson & Johnson, donated its PREZCOBIX® HIV medication (darunavir/cobicistat) for use in research activities aimed at finding a treatment for COVID-19.
Darunavir is a protease inhibitor marketed by Janssen. Anecdotal reports suggest darunavir as potentially having antiviral activity against COVID-19. It is, however, currently approved only for use with a boosting agent, and in combination with other antiretrovirals, for the treatment of HIV-1. Janssen has no in vitro or clinical data to support the use of darunavir as a treatment for COVID-19. The drug is in the process of being evaluated in vitro for any potential activity against the coronavirus.
Antibody therapy drugs
AT-100 (rhSP-D): Airway Therapeutics is exploring its novel human recombinant protein named AT-100 (rhSP-D) as a treatment for coronavirus. The company has announced a filing with the Respiratory Diseases Branch of the National Institutes of Health to evaluate the drug. AT-100 has shown efficacy in preclinical studies in reducing inflammation and infection in the lungs, while also generating an immune response against various respiratory diseases.
TZLS-501: Tiziana Life Sciences is developing its monoclonal antibody named TZLS-501 for the treatment of COVID-19. TZLS-501 is a human anti-interleukin-6 receptor (IL-6R), which helps in preventing lung damage and elevated levels of IL-6. The drug works by binding to IL-6R and depleting the amount of IL-6 circulating in the body thereby reducing chronic lung inflammation.
OYA1: OyaGen’s OYA1 has shown strong antiviral efficacy against coronavirus in laboratory essays. It was found to be more effective than chlorpromazine HCl in inhibiting SARS-CoV-2 from replicating in cell culture. OYA1 was earlier approved as an investigational new drug for treating cancer but abandoned due to lack of efficacy. OyaGen plans to conduct further research on the drug to determine the efficacy in treating coronavirus.
BPI-002: BeyondSpring’s BPI-002 is a small molecule agent indicated for treating various infections including COVID-19. It has the ability to activate CD4+ helper T cells and CD8+ cytotoxic T cells and generating an immune response in the body. If combined with another COVID-19 vaccine, the drug has the ability to generate long-term protection against viral infections. BeyondSpring has filed US patent protection for the drug for treating viral infections.
NP-120 (Ifenprodil): Algernon Pharmaceuticals has announced that it is exploring its NP-120 (Ifenprodil) as a potential treatment COVID-19. Ifenprodil is an N-methyl-d-aspartate (NDMA) receptor glutamate receptor antagonist sold under the brand name Cerocal. It has demonstrated efficacy in improving survivability in mice infected with H5N1.
APN01: A drug candidate developed by APEIRON Biologics named APN01 is being tested in China in a phase one pilot trial as a treatment for COVID-19. APN01 is based on research conducted by a professor at the University of British Columbia for treating SARS. The research revealed that the ACE2 protein was the main receptor for the SARS virus. The clinical trial will test the drug’s efficacy in reducing the viral load in patients. Data from the trial will be used to determine if additional clinical trials are required to be conducted in larger number of patients.
Brilacidin: Innovation Pharmaceuticals announced that it is evaluating Brilacidin, a defensin mimetic drug candidate, as a potential treatment for coronavirus. Brilacidin has shown antibacterial, anti-inflammatory and immunomodulatory properties in several clinical trials. The company is planning to explore research collaborations and seek federal grants to develop the coronavirus drug. It is already investigating the drug for inflammatory bowel disease and oral mucositis in cancer patients. Innovation has signed two material transfer agreements with a university in the US and 12 biocontainment labs in the US for evaluation of Brilacidin as a treatment for COVID-19. One of the biocontainment labs is scheduled to commence testing of the drug in the third week of March.
Leronlimab (PRO 140): CytoDyn is examining leronlimab (PRO 140), a CCR5 antagonist, as a potential coronavirus drug. The drug is already being investigated in phase two clinical trials as a treatment for HIV and has been awarded fast-track approval status by the United States Food and Drug Administration.
BXT-25: Used to treat late-stage acute respiratory distress syndrome (ARDS), BIOXYTRAN announced that it is exploring partners to develop its lead drug candidate, BX-25, as a treatment for Acute Respiratory Distress Syndrome (ARDS) in late-stage patients infected with the coronavirus. The diffusion of oxygen to the blood is comprised in patients suffering from ARDS leading to fluid build-up in the lungs. BX-25 is designed to be 5,000 times smaller than blood cells and efficiently transport oxygen through the body for a period of nine hours before being processed by the liver. The drug can help in supplying oxygen to the vital organs and enable the patient to recover and survive.
The novel coronavirus drugs in various stages of development globally are listed below.
Remdesivir (GS-5734) by Gilead Sciences: An ebola drug developed by Gilead Sciences that was found to be ineffective is now being tested in two phase III randomised clinical trials in Asian countries. The trials are being performed on 761 patients in a randomised, placebo-controlled, double-blind study at multiple hospitals in Wuhan, the epicentre of the novel coronavirus outbreak. The results from the trials are expected to be available over the next few weeks.
According to a report by The New England Journal of Medicine (NEJM), remdesivir, when administered to a coronavirus patient in the US, appeared to have improved the clinical condition. The University of Nebraska Medical Center is also carrying out clinical trials to test the safety and efficacy of the drug. The first patient to be administered the drug is an evacuee from the Diamond Princess cruise ship.
Actemra by Roche to treat coronavirus-related complications: China approved the use of Roche’s Actemra for the treatment of severe complications related to coronavirus. Drugs like Actemra have the ability to prevent cytokine storms or overreaction of the immune system, which is considered as the main reason behind organ failure leading to death in some coronavirus patients. Actemra is also being evaluated in a clinical trial in China, which is expected to enroll 188 coronavirus patients. The clinical trial is expected to be conducted until May 10.
Biocryst Pharma’s Galidesivir, a potential antiviral for coronavirus treatment: The antiviral drug Galidesivir (BCX4430) has shown broad-spectrum activity against a wide range of pathogens including coronavirus. It is a nucleoside RNA polymerase inhibitor that disrupts the process of viral replication. The drug has already shown survival benefits in patients against deadly viruses such as Ebola, Zika, Marburg, and Yellow fever. Galidesivir is currently in advanced development stage under the Animal Rule to combat multiple potential viral threats including coronaviruses, flaviviruses filoviruses, paramyxoviruses, togaviruses, bunyaviruses, and arenaviruses.
Regeneron’s REGN3048-3051 and Kevzara: Discovered by Regeneron, the combination of neutralising monoclonal antibodies REGN3048 and REGN3051 is being studied against coronavirus infection in a first-in-human clinical trial sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). The safety and tolerability of the drug will be studied in 48 patients.
Both the antibodies bind to S-protein of MERS coronavirus. The intravenous administration of the drug in the mouse model of MERS resulted in the high-level neutralisation of the MERS coronavirus in circulating blood with reduced viral loads in the lungs.
Regeneron has partnered with Sanofi to evaluated Kevzara, a fully-human monoclonal antibody, in a phase two/three clinical trial in patients with severe COVID-19 infection. Kevzara is approved for the treatment of rheumatoid arthritis and is known to block the interleukin-6 (IL-6) pathway, which causes an overactive inflammatory response in the lungs of COVID-19 patients.
SNG001 by Synairgen Research: Synairgen Research’s SNG001, an inhaled drug, is planned to be tested by the University of Southampton to treat asthma, chronic obstructive pulmonary disease and lower respiratory tract illnesses caused by coronavirus. SNG001 is a formulation of naturally occurring Interferon-β, which is administered through a nebuliser and is delivered directly to the lungs to reduce the severity of the infection caused by coronavirus.
AmnioBoost by Lattice Biologics: Lattice Biologics is exploring the efficacy of its amniotic fluid concentrate, AmnioBoost, in treating acute respiratory distress syndrome (ARDS) in COVID-19 patients. AmnioBoost was developed for chronic adult inflammatory conditions such as osteoarthritis. The drug has shown efficacy in reducing the inflammatory conditions caused by several diseases including coronavirus. It reduces the production of pro-inflammatory cytokines while boosting the production of anti-inflammatory cytokines.
Thus far, t total of 30 therapies are being tested, including few traditional medicines for coronavirus treatment by Chinese scientists. Chloroquine phosphate has shown efficacy in treating symptoms of the disease, among the 30 therapies. Patients administered with the drug achieved a better drop in fever and shorter recovery time in clinical trials being conducted in hospitals in the Guangdong province and Hunan province.
Enanta Pharmaceuticals :Enanta Pharmaceuticals has announced its plans to develop antiviral drug candidates to treat COVID-19 patients. The company is testing compounds from its existing antiviral compound library for potential efficacy in treating COVID-19. It has also launched a drug discovery programme to develop direct-acting drug candidates to treat COVID-19.
Predictive Oncology: Predictive Oncology has launched an AI Platform for the discovery and development of vaccines against coronavirus. The company has signed an agreement with InventaBioTech to acquire Soluble Therapeutics, which provides it with access to the HSCTM Technology. Predictive will use the HSCTM Technology along with its predictive modeling platform to deploy an AI discovery platform that can screen the ideal combination of additives and excipients for protein formulations.
Emergent BioSolutions :Emergent BioSolutions is developing two plasma-derived product candidates or hyperimmunes using its hyperimmune platforms for the treatment of coronavirus. The hyperimmune platforms have been used previously for the development of several approved products including vaccines for smallpox, botulism, and anthrax. The hyperimmunes are polyclonal antibodies derived from plasma, which are capable of generating an immune response and protecting against infection. Product candidate derived from human plasma is named COVID-HIG, while COVID-EIG is derived from equine plasma. Both will be explored for the treatment of patients with a severe case of infection.
Integral Molecular: Integral Molecular has launched a vaccine programme using its two technology platforms including Shotgun Mutagenesis Epitope Mapping and the Membrane Proteome Array. The technologies will help in understanding the human immune response to the coronavirus and isolate the cellular receptors that enable the virus to spread quickly. The Shotgun technology helps in identifying more than 1,000 binding sites for antibodies, while the Membrane Proteome Array technology is capable of identifying the receptors through which viruses infect cells.
CEL-SCI:CEL-SCI is developing immunotherapy against COVID-19 using its proprietary LEAPS peptide technology, which utilises conserved areas of the coronavirus proteins to generate T-cell responses and reduce viral load. The technology can also be used to develop immunotherapeutic peptides with both antiviral and anti-inflammatory properties. The peptides developed using this technology can help in reducing tissue damage from inflammation caused due to lung infection, which is a major cause of mortality in elderly patients.
Takeda Pharmaceutical Company: Takeda Pharmaceutical Company has announced plans to develop a plasma-derived therapy against coronavirus. The anti-SARS-CoV-2 polyclonal hyperimmune globulin (H-IG) therapy will be designed to treat high-risk patients. The H-IG therapy includes concentrated pathogen-specific antibodies derived from plasma of recovered patients. These antibodies have the potential to generate an immune response when injected into a new patient.
Heat Biologics: Heat Biologics has announced plans to develop a vaccine to treat or prevent coronavirus infection using its proprietary gp96 vaccine platform. The technology is capable of reprogramming live cells to produce antigens that can bind to the gp96 protein and generate an immune response against those antigens.
Pfizer: Pfizer announced that it has identified certain under development antiviral compounds that may be effective in treating coronavirus. The company is planning to partner with a third party to screen and identify potential compounds by the end of March and begin testing in April.
Mateon Therapeutics: Mateon Therapeutics has launched an antiviral response program to develop coronavirus treatments using its therapeutic and artificial intelligence (AI) platforms. It has also established a division, which will adopt a multi-modal approach to developing COVID-19 treatments as well as other future zootonic outbreaks.
Hong Kong University of Science and Technology: The Hong Kong University of Science and Technology has identified several vaccine targets, which can be developed as a treatment for coronavirus. Researchers at the university have identified B-cell and T-cell epitopes, which are capable of generating an immune response against the SARS virus and a similar response against the coronavirus. Some of the epitopes identified may be capable of generating an immune response specifically against COVID-19.
Coronavirus drugs by Columbia University: Researchers at Columbia University have been awarded a $2.1m grant by the Jack Ma Foundation to develop a coronavirus cure. Four different teams at the university will adopt various approaches towards the development of a vaccine against coronavirus.