Q&A - Treatements and vaccins in R&D

Monday 1 June 2020 - Updated on Friday 12 June 2020
The Covid-19 pandemic has led to an unprecedented number of clinical trials of potential treatments and vaccines aim to protect people before exposure to SARS-CoV-2, the virus that causes COVID-19.

Traitements

The Covid-19 pandemic has led to an unprecedented number of clinical trials of potential treatments. As of early May, WHO identified over 1200 registered clinical trials around the world relating to Covid-19, including 721 registered as randomized controlled trials on which 580 that are actively recruiting participants. 

Nearly all these trials are investigating medicines that were originally developed to treat other diseases. For example, hydroxychloroquine is an antimalarial drug also used to treat lupus, lopinavir/ritonavir is used to treat HIV, tocilizumab is used to treat rheumatoid arthritis, and remdesivir was originally developed as a treatment for influenza . Completely new drugs might eventually be developed for Covid-19 but will take much longer. 

Most of the ongoing trials investigate the treatment of Covid-19 patients who are hospitalized, and who have moderate, severe or critical illness. A few trials have been completed and had their results made public, but there have not been any major breakthroughs yet. Most of the trials are comparing a single treatment either to a local standard of care or to placebo. 

A few larger trials seek to compare multiple possible treatments, including the Solidarity trial sponsored by WHO, which includes up to four possible treatment regimens and is recruiting in many countries around the world. Similar national/regional trials with multiple arms are underway such as Recovery  in the UK coordinated by univ of Oxford and the UK research and innovation/NIHR ; Discovery in France and Luxembourg coordinated by INSERM within Reacting consortium and ACTT in the United States. 

A smaller number of trials investigate the treatment of Covid-19 patients who do not need to be hospitalized. Most patients with mild Covid-19 will get well without specific treatments. But particularly in regions with little capacity for advanced care, a strategy that aimed to prevent mild cases from progressing to severe could be very valuable. Investigating this type of strategy would need many participants, and several initiatives are already underway, including AntiCov coordinated by DNDi, which would enroll patients in multiple African countries including trials sponsored by Epicentre (cf infra). 

The outcomes/ results of these dynamic trials will help to inform about the efficacy of drugs candidates;  for instance Remdesivir has been granted as an emergency use authorization by the US FDA for the treatment of severe patients hospitalized. However easy to use treatments (oral vs injectable) will be an important component for access.

Finally, there is also interest in testing medicines as prophylaxis for high-risk health care workers, including a major international trial led by the University of Oxford in which Epicentre is involved (cf infra). 

Vaccines

Vaccines aim to protect people before exposure to SARS-CoV-2, the virus that causes COVID-19. The aim is to help the immune system recognize and destroy the virus when it encounters it thereby preventing infection. There are many different possibilities for the types of vaccines. There are at least eight different types of vaccines being developed against SARS-CoV-2 with different viruses or viral parts.

Given this pandemic, a large number of groups are working on potential vaccines for SARS-CoV-2, with several backed by the Coalition for Epidemic Preparedness Innovations (CEPI). As of today there are at least 120 publicly known projects around the world centered on the development of a vaccine candidate. There are surely many more. Some have already begun the first stage of testing in humans for safety: eight are in clinical trial  (2 mRNA construct in the USA and Germany; 1 DNA plasmid construct in the USA, 1 adeno5 construct in China; 1 chimp adeno construct in the UK in partnership with the Serum Institute of India, 3 inactivated whole virion vaccines in China.

The below is a highlight of these.

  • Moderna, USA. This is a messenger RNA (mRNA) vaccine currently in a phase I clinical trial in Seattle, Washington, USA. In a mRNA vaccine, the nucleic acid is inserted into human cells, which then create many copies of the virus protein; most of these vaccines encode the virus’s spike protein. The study includes 45 healthy volunteers, ages 18 to 55, who are getting two doses 28 days apart. As the company has developed other mRNA vaccines before without major safety concerns, they were able to proceed quickly into Phase I. 
     
  • Inovio, USA. The company has already been working on a DNA vaccine for MERS, which is caused by another coronavirus. Because of this, the company could quickly develop a candidate for SARS-Cov-2. Innovio has begun their Phase I study in 40 volunteers.
     
  • University of Oxford, England. This is a chimpanzee adenovirus vaccine vector (ChAdOx1), developed at Oxford’s Jenner Institute. It is a one dose vaccine and not a replicating virus, so it cannot cause an ongoing infection in the vaccinated individual. A clinical trial with more than 500 participants began in late April. This is a Phase I/II study. The vaccine uses a modified virus to trigger the immune system.
     
  • Institute Pasteur/Themis. This strategy is derived from measles live-attenuated vaccine, a largely safe and effective human vaccine, engineered to express additional antigens including that of SARS-CoV-2.
     
  • Vaccine companies. Johnson & Johnson and Sanofi are both working on a vaccine of their own. The Johnson and Johnson vaccine is an adenovirus vectored vaccine and the company has experience with this platform although no vaccine is licensed with this platform. Pfizer has also teamed up with a German company to develop a vaccine. Their initial clinical trial with 200 participants was approved to start in late April. The two companies began human testing in the United States in early May.


It is important to note that questions concerning the number of doses needed, length of immunity and other critical questions concerning these candidates is not yet known. These are all candidates in development, and this is a new virus to humans, so many of these questions do not yet have responses. There is also no degree of certainty at what level any of the vaccine candidates will actually be immunogenic or clinically efficacious in preventing disease.

At the same time, some clinical trials are underway in the Netherlands and Australia to see whether existing vaccines for tuberculosis (BCG) might also protect against SARS-CoV-2 in healthcare workers. These existing vaccines might boost the immune system to help fight infection, although there’s no evidence yet to confirm this theory which is also referred to non-specific effects of vaccines. 

Epicentre activities

Epicentre is collaborating in different research areas with national authorities and several partners in different African countries.
  
Treatments
For prophylaxis, Epicentre is participating in a global effort implementing the Copcov study   in   one or more African countries.  This international prophylactic study led by the University of Oxford (UK) and funded by the Wellcome Trust aims to test in a large-scale clinical trial the use of Hydroxychloroquine on up to 40,000 healthcare participants at between 50 to 100 sites. Approval from national authorities in Niger is expected by end of May. Ghana is considering participating in this trial.  

For mild-to-moderate cases, Epicentre is proposing a study called Trascov to evaluate with populations  -suspected , confirmed or potential cases of Covid 19 -_various  options therapies vs the  standard of care. This trial is pending authorization from national authorities in Niger as well as pending funding. Results of this trial if approved will be pooled with others generated throughout the international AntiCov  study coordinated by  DNDi which  aims to enroll  3000 patients in at least 15 African countries with 28 sites.
 
Vaccines 
Epicentre is also participating in both formal and informal review panels of different vaccine candidates and may also participate in trials of these vaccines if appropriate and needed. 

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