(Reuters) - With much of the world living in lockdown, the spread of the new coronavirus, SARS-CoV-2, that was first detected in China late last year is beginning to slow in some places. As of April 12, 1.8 million had been infected and 115,000 killed by COVID-19, the disease caused by the virus.

FILE PHOTO: Scientist Linqi Zhang shows a tube with a solution containing COVID-19 antibodies in his lab where he works on research into novel coronavirus disease (COVID-19) antibodies for possible use in a drug at Tsinghua University's Research Center for Public Health in Beijing, China, March 30, 2020. REUTERS/Thomas Peter

While a safe, effective vaccine is still more than a year away, researchers are rushing to repurpose existing drugs and non-drug therapies as well as testing promising experimental drugs that were already in clinical trials.

Even moderately effective therapies or combinations could dramatically reduce the crushing demand on hospitals and intensive care units, changing the nature of the risk the new pathogen represents to populations and healthcare systems. New drugs, together with new diagnostics, antibody tests, patient- and contact-tracing technologies, disease surveillance and other early-warning tools, mean the anticipated next “wave” of the global pandemic does not have to be nearly as bad the first.

More than 70 vaccine candidates are also in development around the world, with at least five in preliminary testing in people. Here are some of the drugs, vaccines and other therapies in development:

*DRUGS*

REMDESIVIR - GILEAD SCIENCES

Antiviral drug, originally developed to combat RNA viruses including respiratory syncytial virus. At least 13 trials underway in China, Europe and the U.S. with preliminary results from two Chinese trials expected as soon as April 2020. A February assessment by the WHO flagged this candidate as the most promising for battling COVID-19.

CAVEATS: Initial data are expected to come from studies of patients with relatively severe COVID-19. Because antivirals work best when patients are healthier, those results may show limited effectiveness.

STATUS: Repurposed Experimental

EARLY RESULTS: 0-3 months

FURTHER READING:

Gilead starts two late-stage studies to test drug for coronavirus

Link: here

Investors await data on coronavirus drugs as market rally builds

Link: here

Gilead asks FDA to revoke orphan drug status for potential coronavirus drug

Link: here

Clinical Trials

Link: here&term=Remdesivir&cntry=&state=&city=&dist=

New England Journal of Medicine, April 2020

Link: here

HYDROXYCHLOROQUINE/CHLOROQUINE

Malaria drug also believed to have antiviral activity. Blocked SARS-CoV-2 entry into cells in an in-vitro experiment. In one small French study, some COVID-19 patients showed improvements but there was no way to know if the drug was the reason. Results published in April from another study in France and one in China found no benefit in patients treated with the drug. Dozens more clinical studies are underway around the world.

STATUS: Repurposed

EARLY RESULTS: 0-3 months

FURTHER READING:

Special Report: Doctors embrace drug touted by Trump for COVID-19, without hard evidence it works

Link: here

Coronavirus drug hopefuls are cheap to make but may be in short supply

Link: here

Clinical Trials

Link: here&term=hydroxychloroquine&cntry=&state=&city=&dist=

Journal of Zhejiang Univ (Med Sci), March 2020

Link: here

Médecine et Maladies Infectieuses, March 2020

Link: here

Nature, February 2020

Link: here

ACTEMRA (TOCILIZUMAB) - ROCHE

Monoclonal antibody approved for rheumatoid arthritis and also for treating the “cytokine storm” immune overresponse in cancer patients. Fifteen registered trials in China, Europe and the U.S. are testing it on COVID-19 patients, alone or in comparison to other therapies. One French trial is looking at 28-day effects on COVID-19 in patients with advanced or metastatic cancer.

STATUS: Repurposed

EARLY RESULTS: 0-3 months

FURTHER READING:

Coronavirus drug hopefuls are cheap to make but may be in short supply

Link: here

Clinical Trials

Link: here

KEVZARA (SARILUMAB) - SANOFI, REGENERON PHARMACEUTICALS

Monoclonal antibody approved for inflammatory arthritis, and in trials targeting the “cytokine storm” immune response in severely ill COVID-19 patients. Regeneron’s chief scientific officer has said initial data on effectiveness could come by late April.

STATUS: Repurposed

EARLY RESULTS: 0-3 months

FURTHER READING:

Data on arthritis drug to treat coronavirus could come within weeks, according to Regeneron executive

Link: here

Exclusive: Sanofi can produce millions of doses of potential coronavirus drug - CEO

Link: here

Sanofi, Regeneron expand testing of potential coronavirus treatment

Link: here

Clinical Trials

Link: here&term=sarilumab&cntry=&state=&city=&dist=

JAKAVI (RUXOLITINIB) - NOVARTIS, INCYTE

Developed to treat inflammatory and autoimmune diseases, and in late-stage development as a cream for atopic dermatitis. One trial each in Canada and Mexico will test the drug in COVID-19 patients with severe respiratory symptoms associated with the “cytokine storm” immune response, with preliminary results expected by June 2020. In the United States, Novartis established a managed access program for use in severe/very severe COVID-19 illness on April 7.

STATUS: Repurposed

EARLY RESULTS: 0-3 months

FURTHER READING:

Novartis, Incyte join repurposing wave to give Jakavi a trial run in COVID-19

Link: here

Clinical Trials

Link: here

KALETRA (LOPINAVIR/RITONAVIR) - ABBVIE

Antiviral combination used to treat and prevent HIV infections. More than twenty trials around the world are testing the drug as a COVID-19 treatment or post-exposure prophylaxis for people with high-risk close contact with a confirmed case. Initial results expected as soon as May 2020.

CAVEATS: One randomized controlled trial in China published results in March showing no differences in viral load or 28-day mortality among 199 patients. Median time to clinical improvement was one day shorter in patients taking the drug. However the same investigators, doctors at Jinyintan Hospital in Wuhan, said in April that they believe Kaletra, as well as a second drug, bismuth potassium citrate, helped some of the COVID-19 patients they treated.

STATUS: Repurposed

EARLY RESULTS: 0-3 months

FURTHER READING:

Key China coronavirus hospital says HIV drug beneficial to patients

Link: here

Mylan waives exclusive U.S. distribution rights for potential COVID-19 therapy

Link: here

Clinical Trials

Link: here&term=Kaletra&cntry=&state=&city=&dist=

New England Journal of Medicine, March 2020

Link: here

RHACE2 APN01 - APEIRON BIOLOGICS

A recombinant human angiotensin converting enzyme 2 (rhACE2) under Phase-2 clinical development in ALI (Acute Lung Injury) and PAH (Pulmonal arterial hypertension). This synthetic version of the human protein that the novel coronavirus uses to enter cells is being tested in Austria to see if it can block viral entry and decrease viral replication in COVID-19 patients, reducing deaths or need for mechanical ventilation. Preliminary results from the trial that was announced on April 2 are expected in September 2020.

STATUS: Experimental

EARLY RESULTS: 3-6 months

FURTHER READING:

Clinical Trial

Link: here&cond=COVID&draw=2&rank=1

CAMOSTAT MESYLATE - UNIVERSITY OF AARHUS, DENMARK

Protease inhibitor licensed in Japan and South Korea to treat chronic pancreatitis. In vitro experiments found it blocks a mechanism SARS-Cov-2 uses to enter human cells. As of early April, an estimated 180 COVID-19 patients aged 18-110 were being recruited at nine locations in Denmark for a phase 2a trial that will examine 30-day changes in disease severity and mortality, with results expected by December 2020. The University of Tokyo also announced plans for a trial of camostat mesylate and a related drug, nafamostat mesylate, starting as early as April 2020.

STATUS: Repurposed

EARLY RESULTS: 6-12 months

IFX-1 - INFLARX

Monoclonal antibody targeting complement activation product C5a. Designed to block a mechanism of inflammation, the drug is also in clinical trials for Hidradenitis Suppurativa, ANCA-associated vasculitis and Pyoderma Gangraenosum. In early April, a trial in the Netherlands launched to test IFX-1 in patients with severe COVID-19 pneumonia, with preliminary results expected in late October 2020.

STATUS: Experimental

EARLY RESULTS: 6-12 months

ASPIRIN, CLOPIDOGREL, RIVAROXABAN, ATORVASTATIN, OMEPRAZOLE - IMPERIAL COLLEGE LONDON

Trial of cardioprotective drugs to prevent direct damage to the heart muscle that appears to drive the severity of COVID-19 in certain patients as well as their likelihood of needing invasive critical care. The trial will include more than 3,000 patients in the UK, with a completion date of March 30, 2021.

EARLY RESULTS: 9-12 months

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*VACCINES*

MRNA 1273 - MODERNA/NIAID

RNA vaccine made with messenger-RNA (mRNA) encoding the spike protein of SARS-CoV-2 encapsulated in a lipid nanoparticle. The phase 1 trial with 45 subjects aged 18-55 at three locations in the U.S. will evaluate the vaccine’s safety and provide early data on the immune response it induces. Trial completion is anticipated to be June 1, 2020.

STATUS: Experimental

EARLY RESULTS: 0-3 months

FURTHER READING:

J&J, Moderna sign deals with U.S. to produce huge quantity of possible coronavirus vaccines

Link: here

Clinical Trial

Link: here

NVX-COV2373 - NOVAVAX

Novavax said its Matrix-M adjuvant would be used with the vaccine candidate - NVX-CoV2373 - to enhance immune responses. Trial in 130 adults is expected to begin in mid-May with with preliminary immunogenicity and safety results in July, according to the company.

CAVEATS: Strong immunogenicity in animal tests, but might require two doses in humans, which would limit supply.

STATUS: Experimental

EARLY RESULTS: 0-3 months

FURTHER READING:

Novavax to start human trial for novel coronavirus vaccine

Link: here

LENTIVIRAL MINIGENE VACCINES (LV-SMENP) - SHENZHEN GENO-IMMUNE MEDICAL INSTITUTE

Engineered minigenes encoding viral antigens; lentiviral vector designed to infect dendritic and T cells to induce immunity. The trial in 100 adults in Shenzen, China, is expected to be complete by July 31, 2020.

STATUS: Experimental

EARLY RESULTS: 3-6 months

BCG TUBERCULOSIS VACCINE - MURDOCH CHILDREN’S RESEARCH INSTITUTE; UMC UTRECHT

Bacillus Calmette-Guérin tuberculosis vaccine that induces a broad innate immune-system response, which has been shown to protect against infection or severe illness with other respiratory pathogens. Large trials in Australia and the Netherlands are testing whether using BCG to rev-up immune defenses in health workers and the elderly reduces unplanned absenteeism, respiratory illnesses including COVID-19, severe illnesses and deaths. Two additional trials by the Max Planck Institute in Germany of a TB vaccine candidate, VPM1002, are in the works.

STATUS: Repurposed

EARLY RESULTS: 3-6 months

FURTHER READING:

Explainer: How an old tuberculosis vaccine might help fight the new coronavirus

Link: here

Clinical Trials

Link: here&term=BCG&cntry=&state=&city=&dist=

INO-4800 - INOVIO PHARMACEUTICALS, COALITION FOR EPIDEMIC PREPAREDNESS INNOVATIONS (CEPI)

DNA plasmid vaccine delivered into the skin via a patch-style electroporation device. A clinical trial launched on April 3 could yield preliminary data by late summer, according to the company, which has said it can manufacture 1 million doses by year-end for additional trials and emergency use.

STATUS: Experimental

EARLY RESULTS: 3-6 months

FURTHER READING:

Potential COVID-19 vaccine shows promise in mouse study

Link: here

Clinical Trial

Link: here

AD5-NCOV - CANSINO BIOLOGICAL INC./BEIJING INSTITUTE OF BIOTECHNOLOGY

Non-replicating viral vector. A single-center phase 1 trial with 108 subjects aged 18-60 in Wuhan, Hubei, China, started in March to test the safety and immune responses generated by a recombinant vaccine that uses another respiratory virus, adenovirus, as a vector. On April 12, a randomized controlled phase 2 trial with 500 participants launched to test varying doses against placebo. Phase 1 completion is in late December 2020, and phase 2 results are expected in January 2021.

STATUS: Experimental

EARLY RESULTS: 6-12 months

CHADOX1 - UNIVERSITY OF OXFORD

Non-replicating chimpanzee adenovirus vector. Phase 1/2 trial with 510 subjects aged 18-55 at four centers in the United Kingdom. The trial will test safety and immunogenicity of one or two doses of the vaccine, and is expected to be completed in May 2021.

STATUS: Experimental

EARLY RESULTS: 12-18 months

FURTHER READING:

Epidemic response group ups coronavirus vaccine funding to $23.7 million

Link: here

Epidemic response group ups coronavirus vaccine funding to $23.7 million

Link: here

Clinical Trial

Link: here

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*NON-DRUG THERAPIES*

CONVALESCENT PLASMA

Blood plasma from recovered COVID-19 patients is transfused into patients who are currently ill, in the hope the freshly-made antibodies it contains will help fight the virus. The method has been used for more than 100 years and carries little risk of harm or side effects. Small case studies suggest it may help reduce virus levels, and controlled trials are in progress in China, Europe and the United States to gather stronger evidence for a benefit. Results published in April from a study in 10 patients with severe illness in China found significant improvement compared to similar patients who did not receive the treatment.

CAVEATS: Immediately available and already in limited use, but supply of plasma from recovered patients may not be sufficient to meet all needs. Further studies of recovered patients must also determine if everyone produces a full immune response to the infection, including “neutralizing antibodies,” at sufficiently high levels to become donors.

EARLY RESULTS: 0-3 months

FURTHER READING:

Why U.S. hospitals see promise in plasma from new coronavirus patients

Link: here

Clinical Trials

Link: here&term=convalescent+plasma&cntry=&state=&city=&dist=&Search=Search

NKG2D-ACE2 CAR-NK CELLS - CHONGQING PUBLIC HEALTH MEDICAL CENTER, CHONGQING SIDEMU BIOTECHNOLOGY TECHNOLOGY

NKG2D receptor for the immune system’s natural killer (NK) cells paired with the ACE-2 receptor that the coronavirus uses to enter human cells. A multicenter Phase 1/2 trial in 90 patients is testing whether this cell therapy can prevent the SARS-CoV-2 virus from entering cells and multiplying, and will look at efficacy over 28 days in patients with severe or critical COVID-19 pneumonia.

STATUS: Experimental

EARLY RESULTS: 0-3 months

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*TESTING*

SEROLOGY/ANTIBODY TESTING

Governments and academic groups have started to test blood for antibodies indicating that a person has been exposed to the new virus, with or without showing symptoms. The presence of antibodies indicates past infection, but separate, ongoing research is needed to know what type and concentration of virus-neutralizing antibodies protect against a new infection, whether all infections produce a full antibody response, and how long protection might last.

Wide serology testing for antibodies will soon provide a broader understanding of the scope and dynamics of the pandemic, help identify which recovered patients may have some immunity to reinfection and for how long, and also help identify the neutralizing antibodies that could become templates for monoclonal antibody therapies as well as models for desired responses from a vaccine candidate. Data from serology testing are expected to begin appearing within weeks.

CAVEATS: Early data on COVID-19 patients in China suggests that they develop varying amounts of antibodies in response to infection. One pre-publication report analyzed plasma from 175 patients and found that a sign of inflammation correlated with higher antibody titers and that younger patients were less likely to produce large amounts of antibodies. Experts think instances of “reinfection” in recovered patients are more likely relapses in patients whose bodies had not cleared the virus. Data is still lacking on whether mild or symptomless infections generate meaningful antibody responses or protection.

STATUS: Experimental

EARLY RESULTS: 0-12 months

FURTHER READING:

The Lancet Infectious Diseases, March 2020

Link: here

Preprint, March 2020

Link: here

Preprint, April 2020

Link: here

Clinical Trial, U.S.

Link: here

Clinical Trial, France

Link: here

Clinical Trial, France

Link: here

Clinical Trial, France

Link: here

Clinical Trial, UK

Link: here

Clinical Trial, Italy

Link: here

Clinical Trial, Belgium

Link: here