27th May 2020

With the global number of COVID-19 cases approaching 5 million and more than 300,000 deaths,1 it will come as no surprise that an enormous amount of time, effort and money is being spent on finding effective treatments for this terrible disease. All around the world, there is a concerted effort to develop a vaccine; to find drugs and drug combinations to treat those with severe respiratory symptoms; and also to investigate other prophylactic treatments that will protect people working on the front line who are exposed to huge viral loads.

A quick search on the clinical trials registry, ClinicalTrials.gov, reveals an astonishing 1684 studies involving COVID-19 going on around the world. Not all of these are trials investigating drug treatments – some are diagnostic and epidemiological studies, among others – but nevertheless, this is an indication of the enormous push over the last few months by governments, research organisations, and the pharmaceutical industry to find effective treatments as quickly as possible.  

In the long-term, a vaccine against COVID-19 is extremely important, because prevention is obviously preferable to cure. There are groups all around the world developing COVID-19 vaccines of various sorts, including in China, the US, Canada, Australia, Brazil, Germany and at Oxford University in the UK.2   

In the shorter-term, there are two very urgent needs: effective treatments for those suffering with severe COVID-19 symptoms, and prophylactic treatments to protect those at high risk of infection. This latter group includes frontline healthcare and social care workers who may be exposed to high levels of virus, and patients who are hospitalised for reasons other than COVID-19.       

Re-purposing licensed treatments to address COVID-19

Because of the great urgency in the need for treatments, and the length of time it takes to develop new drugs, it makes sense to re-purpose existing therapies which may show promise against the COVID-19 virus. All around the globe, this is exactly what is taking place in clinical trials right now, with many others being planned.

Drugs being investigated in many clinical trials in several countries include lopinavir-ritonavir and azithromycin. Lopinavir-ritonavir is a combination anti-retroviral medicine used for the treatment of HIV,3 so has the potential to be effective against COVID-19 which is also a retrovirus (a virus that has RNA as its genetic material). Azithromycin is a broad-spectrum antibiotic, but it also has the effect of inhibiting protein synthesis which could stop viruses replicating.4

Some preclinical research showed that hydroxychloroquine, an anti-malaria drug which is also used to treat other conditions such as rheumatoid arthritis and lupus,5,6 has anti-COVID-19 properties.7 However, the World Health Organization (WHO) has just paused studies of hydroxychloroquine after The Lancet published an observational registry study showing an increase in mortality for COVID-19 patients treated with this agent compared with control patients.8

Other areas of focus for clinical trials in COVID-19 patients include monoclonal antibodies (for example, GSK is planning to trial otilimab - a drug developed for rheumatoid arthritis); convalescent plasma infusion (plasma containing COVID-19 antibodies from patients who have recovered); mesenchymal stem cells (MSCs) to promote the regeneration of damaged lung tissue; and cell-based immunotherapy.2 

This is in no way intended to be a comprehensive list, but merely to give an indication of the huge breadth of research going on internationally to fast-track effective treatments and treatment combinations.  

Prophylactic treatments to protect those at high risk of infection

Protecting frontline healthcare and social care workers, and vulnerable patients, from contracting COVID-19 is vital in the fight against COVID-19. With this aim, many clinical trials are investigating prophylactic treatments that reduce the risk of these groups being infected, or that lower the severity of symptoms if infected. As well as many studies of the prophylactic effect of hydroxychloroquine, the BCG vaccine is one area of focus in several countries, including Egypt, The Netherlands, Colombia, and Australia.2 The BCG vaccine is usually given to prevent tuberculosis, but there is increasing evidence that the BCG vaccine has beneficial non-specific immunomodulatory properties which protect against respiratory infections. The rationale, therefore, is that BCG may prevent severe COVID-19 disease in those at high risk of infection.9

New drug development in the fight against COVID-19 

In parallel with trials of existing treatments, many pharmaceutical companies are pushing forward with the development of new drugs to treat COVID-19, including 4D pharma plc; R-Pharm International, LLC; Ansun Biopharma, Inc. and Vicore Pharma - a Swedish company. Vicore Pharma has just received approval from the MHRA for a clinical trial of VP01 named ‘ATTRACT’ (Angiotensin II Type Two Receptor Agonist Covid-19 Trial)10. The study will enrol hospitalised COVID-19 patients who are being treated with basic respiratory care but are not on mechanical ventilation. The researchers believe that VP01 - a first-in-class low molecular weight angiotensin II receptor type 2 (AT2R) agonist - could ameliorate the symptoms of COVID-19.

Further reading

A highly detailed map detailing all the different strategic approaches to combating COVID-19 has been developed by RA Capital – it’s a powerful visualization of just how much work is going on globally: https://racap.com/covid-19

With such a huge global effort to find effective treatments for those suffering from COVID-19, and those at high risk of infection, we can all find some comfort in the real possibility that in the not-too-distant future, fewer people will become seriously ill and fewer people will die. In the short-term, protecting the most vulnerable is an imperative, and in the long-term the promise of a vaccine will hopefully become a reality and we can all feel safe from COVID-19.   

References

1. European Centre for Disease Prevention and Control. COVID-19 situation update worldwide, as of 22 May 2020. Available at https://www.ecdc.europa.eu/en/geographical-distribution-2019-ncov-cases

2. ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/results?cond=COVID-19#

3. Lopinavir-ritonavir Summary of Product Characteristics. Available at:   https://www.ema.europa.eu/en/documents/product-information/kaletra-epar-product-information_en.pdf

4. Health Europa. Could azithromycin prevent NHS workers from developing COVID-19? 8 April 2020. Available at: https://www.healtheuropa.eu/azithromycin-prevent-nhs-workers-developing-covid-19/99271/

5. Centers for Disease Control and Prevention. Medicines for the Prevention of Malaria While Traveling: Hydroxychloroquine (Plaquenil™). Available at: https://www.cdc.gov/malaria/resources/pdf/fsp/drugs/hydroxychloroquine.pdf

6. Hydroxychloroquine Summary of Product Characteristics. Available at: https://www.medicines.org.uk/emc/product/477/smpc 

7. Liu J, Cao R, Xu M, et al. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov 2010; 6: 16. Available at: https://www.nature.com/articles/s41421-020-0156-0     

8. Mehra MR, Desai SS, Ruschitzka F, et al. Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis. Available at:  https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31180-6/fulltext

9. Curtis N, Sparrow A, Ghebreyesus TA, Netea MG. Considering BCG vaccination to reduce the impact of COVID-19. Lancet. 2020 Apr . doi:10.1016/s0140-6736(20)31025-4.

10. McKee S. Vicore Pharma bags MHRA nod for COVD-19 trial in record time. PharmaTimes. 1st May 2020. Available at:  http://www.pharmatimes.com/news/vicore_pharma_bags_mhra_nod_for_covd 19_trial_in_record_time_1339373