The lifeline pipeline: status of vaccines development for COVID-19
Christine Soares
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 May 13, 4.3 million had been infected and 290,000 killed by COVID-19, the disease caused by the virus.
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 as the first.
VACCINES
1. MODERNA/NIAID - mRNA 1273
TYPE: VACCINE
STATUS: EXPERIMENTAL
EARLY RESULTS: 0-3 MONTHS
RNA vaccine made with messenger-RNA (mRNA) encoding the spike protein on the surface of the new coronavirus (SARS-CoV-2) and delivered via a lipid nanoparticle. The phase 1 trial with 45 subjects aged 18 to 55 at three locations in the United States 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.
2. NOVAVAX-NVX-CoV2373
TYPE: VACCINE
STATUS: EXPERIMENTAL
EARLY RESULTS
0-3 MONTHS
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.
3. BIONTECH/PFIZER - BNT162
TYPE: VACCINE
STATUS: EXPERIMENTAL
EARLY RESULTS: 0-3 MONTHS
Based on messenger RNA encoding viral proteins, this candidate started trials in Germany in late April, and U.S. trials in early May. Pfizer already collaborates with BioNTech to develop mRNA-based vaccines for influenza. Pfizer has said it hopes to receive emergency authorization from the U.S. Food and Drug Administration for the new vaccine as early as October, and could distribute up to 20 million doses by the end of 2020, with an eye toward producing hundreds of millions of doses next year.
4. SHENZHEN GENO-IMMUNE MEDICAL INSTITUTE - Lentiviral Minigene Vaccines (LV-SMENP)
TYPE: VACCINE
STATUS: EXPERIMENTAL
EARLY RESULTS: 3-6 MONTHS
Engineered minigenes encoding viral antigens; lentiviral vector designed to infect dendritic and T cells - key components of the immune system - to induce immunity. The trial in 100 adults in Shenzen, China, is expected to be complete by July 31, 2020.
5. MURDOCH CHILDREN'S RESEARCH INSTITUTE; UMC UTRECHT - BCG tuberculosis vaccine
TYPE: VACCINE
STATUS: REPURPOSED
EARLY RESULTS: 3-6 MONTHS
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.
6. INOVIO PHARMACEUTICALS, COALITION FOR EPIDEMIC PREPAREDNESS INNOVATIONS (CEPI) - INO-4800
TYPE: VACCINE
STATUS: EXPERIMENTAL
EARLY RESULTS: 3-6 MONTHS
DNA plasmid vaccine delivered through the skin via a patch-style device using a brief low-voltage electronic pulse to induce cell membranes to open, making them more receptive, in theory, to accepting the vaccine's genetic material. 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.
7. CANSINO BIOLOGICAL INC./BEIJING INSTITUTE OF BIOTECHNOLOGY - AD5-nCov
TYPE: VACCINE
STATUS: EXPERIMENTAL
EARLY RESULTS: 6-12 MONTHS
Non-replicating viral vector. A single-center phase 1 trial with 108 subjects aged 18 to 60 in Wuhan, China, started in March to test the safety and immune responses generated by a recombinant vaccine that uses another respiratory virus, adenovirus, to deliver the vaccine material. On April 12, a randomized controlled phase 2 trial with 500 participants launched to test varying doses against placebo. Phase 1 completion is expected in late December 2020, and phase 2 results are expected in January 2021.
8. SANOFI, GSK - Adjuvanted vaccine candidate
TYPE: VACCINE
STATUS: EXPERIMENTAL
EARLY RESULTS: 6-12 MONTHS
In mid-April, two of the world's largest vaccine makers announced they would join forces to create and test six candidates built on technologies already proven in flu vaccines. In all candidates, Sanofi's recombinant S-protein COVID-19 antigen will get a boost from GSK's AS03 adjuvant. Scientists and public health experts are already warning that it could be tricky to induce a strong, effective immune response to the SARS-CoV-2 virus, particularly in the elderly and others with weakened immune systems, so the adjuvant enhancement could help. The resulting vaccine might also require just one dose instead of two, which could stretch supplies. The companies plan to start trials in the second half of 2020 and complete development by second half of 2021.
CAVEATS: The ASO3 adjuvant was in GSK's 2009 Pandemrix flu vaccine used in Europe. But only a handful of adjuvanted vaccines are licensed in the U.S., and none containing ASO3. The exception is a flu vaccine approved in 2013 and stockpiled by the U.S. for use in the event of an H5N1 avian flu pandemic.
9. UNIVERSITY OF OXFORD - ChAdOx1
YPE: VACCINE
STATUS: EXPERIMENTAL
EARLY RESULTS: 12-18 MONTHS
Non-replicating chimpanzee adenovirus vector. Phase 1/2 trial with 510 subjects aged 18 to 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.
DRUGS
1. GILEAD SCIENCES – Remdesivir
TYPE: DRUG
STATUS: REPURPOSED EXPERIMENTAL
EARLY RESULTS: 0-3 MONTHS
Antiviral drug given by infusion previously failed as an Ebola treatment but showed promise against certain coronaviruses in animal studies. In the first large, randomized COVID-19 trial, remdesivir led to a statistically significant reduction in recovery time of hospitalized patients compared with a placebo, demonstrating that it does impact the virus. Based on that data, the FDA issued an emergency use authorization for the drug despite mixed results from other smaller studies. More than a dozen trials underway in China, Europe and the United States with further data expected later this month.
CAVEATS: Initial data is expected to come from studies of patients with relatively severe COVID-19.
2. ABBVIE - Kaletra (lopinavir/ritonavir)
TYPE: DRUG
STATUS: REPURPOSED
EARLY RESULTS: 0-3 MONTHS
Antiviral combination used to treat and prevent HIV infections. More than 20 trials around the world are testing the therapy as a COVID-19 treatment or for post-exposure prevention for those with high-risk close contact with infected people. Initial results expected as soon as May 2020.
CAVEATS: One randomized controlled trial in China found no differences in viral load or 28-day mortality among 199 patients, according to results published in March. Median time to clinical improvement was one day shorter in patients taking the drug. However, the same 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.
3. Hydroxychloroquine / chloroquine
TYPE: DRUG
STATUS: REPURPOSED
EARLY RESULTS: 0-3 MONTHS
An old malaria drug that also treats lupus and rheumatoid arthritis is believed to have antiviral as well as anti-inflammatory activity. Blocked the novel coronavirus' (SARS-CoV-2) entry into cells in an in-vitro experiment. In one small French study, some COVID-19 patients showed improvement 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.
CAVEATS: Health experts caution it should never be used without a prescription and could lead to dangerous side effects on the heart.
4. ABBVIE- Kaletra (lopinavir/ritonavir)
TYPE: DRUG
STATUS: REPURPOSED
EARLY RESULTS: 0-3 MONTHS
Antiviral combination used to treat and prevent HIV infections. More than 20 trials around the world are testing the therapy as a COVID-19 treatment or for post-exposure prevention for those with high-risk close contact with infected people. Initial results expected as soon as May 2020.
CAVEATS: One randomized controlled trial in China found no differences in viral load or 28-day mortality among 199 patients, according to results published in March. Median time to clinical improvement was one day shorter in patients taking the drug. However, the same 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.
5. Camostat mesylate
TYPE: DRUG
STATUS: REPURPOSED
EARLY RESULTS: 0-3 MONTHS
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. A phase 2a trial launched in early April by Aarhus University will examine 30-day changes in disease severity and mortality, with results expected by December 2020. The University of Tokyo also plans a trial of camostat mesylate and a related drug, nafamostat mesylate. A Yale trial in outpatients who test positive for SARS-CoV-2 will look at whether the drug keeps viral loads low, which could help prevent mild illness from becoming severe. That could also make it a good prophylactic. A long safety track record adds to this drug's appeal.
6. ROCHE: Actemra (tocilizumab)
TYPE: DRUG
STATUS: REPURPOSED
EARLY RESULTS: 0-3 MONTHS
Monoclonal antibody approved for rheumatoid arthritis and also used to treat a dangerous overreaction of the immune system called a "cytokine storm" in cancer patients receiving a type of therapy that can trigger that response. COVID-19 triggers a similar response in some patients who have fared poorly. Actemra targets interleukin-6 (IL-6), which is believed to play a role in inflammation. Registered trials in China, Europe and the United States 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 cancer.
7. SANOFI, REGENERON PHARMACEUTICALS - Kevzara (sarilumab)
TYPE: DRUG
STATUS: REPURPOSED
EARLY RESULTS: 0-3 MONTHS
Monoclonal antibody approved for rheumatoid arthritis that targets (IL-6). In trials against the cytokine storm immune response in severely ill COVID-19 patients. Early results announced in late April suggest a benefit in the most critically ill patients.
CAVEATS: Based on review of early data showing little benefit for patients who were severely ill but not in critical condition, the companies announced they would continue the trial only in critical patients.
8. NOVARTIS, INCYTE - Jakavi (ruxolitinib)
TYPE: DRUG
STATUS: REPURPOSED
EARLY RESULTS: 0-3 MONTHS
From a class of drugs known as JAK inhibitors, Jakavi is approved to treat the rare bone marrow cancers myelofibrosis and polycythemia vera and is in late-stage development as a cream for atopic dermatitis. Trials in Canada and Mexico will test the drug in COVID-19 patients with severe pneumonia 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.
9. APEIRON BIOLOGICS - RhACE2 APN01
TYPE: DRUG
STATUS: EXPERIMENTAL
EARLY RESULTS: 3-6 MONTHS
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 the need for mechanical ventilation. Preliminary results from the trial are expected in September 2020.
10. PHARMAMAR - Aplidin (plitidepsin)
TYPE: DRUG
STATUS: REPURPOSED
EARLY RESULTS: 3-6 MONTHS
A map of the virus' interactions inside the human body flagged plitidepsin among several compounds that block a key human protein it needs to infect cells. Aplidin, a cancer therapy approved in Australia, had already shown activity against a different coronavirus in lab studies and was about to enter COVID-19 trials in Spain when the protein-mapping study supporting its potential was published in late April.
11. INFLARX - IFX-1
TYPE: DRUG
STATUS: EXPERIMENTAL
EARLY RESULTS: 6-12 MONTHS
Monoclonal antibody designed to block a mechanism of inflammation. 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. It is also being tested in other inflammatory conditions.
12. IMPERIAL COLLEGE LONDON - Aspirin, Clopidogrel (Plavix), Rivaroxaban (Xarelto), Atorvastatin (Lipitor), Omeprazole (Prilosec)
TYPE: DRUG
EARLY RESULTS: 9-12 MONTHS
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 United Kingdom, with a completion date of March 30, 2021.
Check all the details as well as updates here
Published: April 13, 2020
Updated: May 12, 2020
