The challenge of finding medicines and vaccines to beat Covid-19

The pharmaceutical and biotechnology industries have a long tradition of developing medicines and vaccines to treat and prevent infectious diseases. At the time of writing, the international register of clinical trials, lists some 585 clinical studies (active or recruiting) employing vaccines or medicines to combat Covid-19. This is a remarkable number given that the first known case of Covid-19 was only in November 2019.

The race against time

Given the urgency of finding medicines against Covid-19, pharmaceutical companies are stepping up to this challenge using a variety of approaches:

  • They are trying to find out whether any of the medicines currently approved for use for viral infections (such as HIV AIDS) might also be effective against Covid-19.

  • Companies are sharing a range of candidate anti-viral drugs that are either still at an early stage of development in other infections, or that have been through clinical trials but not found to be adequately effective, to see if they can be useful against Covid-19.

  • They are seeing whether any approved medicines that were developed for other diseases might also possess anti-Covid-19 properties.

  • Companies are working through the hundreds of thousands of candidate drugs that have been synthesised over decades, but not selected for development, to determine whether any of these are active against the virus.

  • There are a number of collaborations with Artificial Intelligence groups in biotech companies, universities and research establishments to discover entirely new chemical and biological entities that might become medicines.

It is important that medicines are shown to be clinically effective and adequately safe. Anecdotal information, whilst interesting, is no substitute for properly conducted clinical studies.

Given the urgency of the coronavirus pandemic and the clear clinical symptoms and degree of infection that can be measured, the time taken to evaluate a new medicine can be considerably shortened from the usual three to five year time scale.

However, it remains essential to safeguard patients that the results of these clinical trials are scrutinized by independent authorities. Government Regulatory Agencies throughout the world have made special arrangements to agree accelerated pathways in the design of the studies and to speed up the review of these trials so to achieve the earliest possible access to treatments whilst ensuring that they are adequately safe.

Whilst the situation is changing rapidly, current clinical trials include:

  • Studying an antimalarial drug Chloroquine;

  • Trying combinations of 4 anti-viral drugs that have been successfully used to treat HIV AIDS or SARS or Ebola virus infections and;

  • Investigating a range of medicines known as monoclonal antibodies which may provide support to patients;

It is important to note that just because a drug has been shown to kill the virus in laboratory experiments does not mean that it will necessarily be clinically effective. For example, it may not be adequately absorbed into the body, or reach the target site of the infection in adequate concentration, or it may be rapidly excreted from the body before it can perform its action. So we have to expect that there will be many failures as well as successes in these trials.

How Viruses work

Viruses, unlike bacteria, cannot survive and multiply in nutrient environments such as food and drink. To grow, a virus needs to use the replication mechanism present in a human (or animal) cell. The process starts with the virus binding to the surface of the host cell. The virus then enters the cell where its nuclear material (in the case of the coronavirus; it’s RNA) unwraps). The RNA is replicated within the cell and then each replicate is packaged into new virus particles. These are discharged from the cell to invade other host cells and hence spread the infection.

Understanding the biochemistry of each of these steps has resulted in the discovery of drug substances that can interfere with the various stages involved with viral replication. However, because some of the processes involved are common to both the virus and to the host cell, many of the drugs that can kill the virus would not be adequately safe as a medicine. Having identified hundreds (even thousands) of potential drug candidates, scientists must then test them in the laboratory before they can be safely tested in clinical trials in patients. Classically these trials take between three and five years.

Developing a Vaccine

Vaccines to protect against a number of viral infectious diseases have been developed over many years e.g. Polio, Yellow Fever, Mumps, Measles.

The concept behind a vaccine is to inject a tiny amount of protein form of the virus, to trigger the body’s innate immune system to recognise this as “an enemy”. Our bodies then orchestrate a variety of responses to kill the virus and stop the invasion.

Importantly, this trains the immune system to recognise the virus if it strikes again – which produces an immunity to the disease.

Most of the “older” vaccines (called “Live-Attenuated Viruses ,LAVs) are produced by growing the viruses in cell culture, extracting the viruses from the cells then “attenuating” the virus using chemicals and/or heat such that, although the virus loses its capability to reproduce, it retains those protein characteristics that are  essential to adducing an immune response when vaccinated.

Vaccine development: a mixed picture

Whilst this technique has proved successful for a range of viral infective diseases, there are viruses’ that -despite decades of research- we still do not have effective vaccines. Very recently, a new approach called “ribonucleic acid (RNA) technology has been used.

The technique involves identifying the key genetic components in the virus that stimulate an immune response; manufacturing these RNA components and then formulating them in a delivery system to be injected as a vaccine. Some of these vaccines are “self-amplifying mRNA vaccines” which continue to “tweak” the immune reposes for days after injection resulting in higher immunity levels. At least five of these vaccines are at a stage where they can shortly be tested in volunteers. In addition, there is a lot of work going on developing other types of vaccine using different techniques.

A Grand Alliance against Covid -19

The speed with which companies and research institutions have moved to produce a significant number of vaccine candidates is impressive fact unprecedented. This is largely due to the state of pandemic preparedness that the medical scientific community has established in recent years, especially following the SARS and the Ebola outbreaks.

It is only ten weeks since scientists around the world received the genetic code for Covid-19. The fact that over 40 vaccines candidates, resulting from collaborations with more than 50 research institutes/biotech/pharmaceutical companies are being evaluated, is testament to the willingness to prioritise this research to defeat a common enemy. It seems likely that the most promising candidate vaccines will be identified from preliminary studies in humans by summer 2020, and that major clinical trials can start in the autumn.

One challenge is to provide massive scale up and manufacturing facilities to cope with the global demand for such vaccines. Historically the pharmaceutical industry is highly competitive and protects its discoveries by widespread patenting of its inventions.

However, in the case of coronavirus medicines and vaccines, companies have stated that they will ensure that patents do not get in the way of progress, that they will share knowledge and expertise and that the prices of the products that emerge will be fair and reasonable. Once these products are approved for use, the challenge will be as to whether national healthcare infrastructures will be sufficient to handle their administration and use…especially in the developing world.

We are particularly fortunate in Wales to have developed a network of centres of clinical excellence that can not only provide expertise in diagnosis and treatment but also in conducting clinical trials. Last year, through the Bevan Commission, we established a new Wales Government sponsored, organisation; Respiratory Innovation Wales (RIW).

Whilst its focus is on conditions such as Asthma and COPD its understanding of respiratory disease is of especial value in treating Covid-19 infections.

In conclusion, whilst there are great challenges to finding an effective vaccine(s) to protect against Covid-19 and to find medicines that are truly effective and adequately safe to treat infected patients, the biotech and pharmaceutical industry is demonstrating a great willingness to meet this challenge. It is heartening to see so many universities, research institutes, governments and medical charities around the world working closely together. Once the Covid-19 crisis is over can this spirit of collaboration be adopted for the other major diseases that afflict so many people worldwide?

Prof Trevor M Jones CBE is a Bevan Commissioner. He is a former R&D Director of the Wellcome Foundation, a Director of Allergan Inc ,the Wales Life Sciences Investment Fund and Director General of The Association of the British Pharmaceutical Industry (ABPI), advisor to UK and EU Governments. Professor Jones is well known internationally for his activities in clinical research and drug discovery and development in the pharmaceutical industry. He has served on many Committees including the UK Government Medicines Commission. Chair of the UK Genetics Advisory Board, the Council of King’s College, London and as Commissioner at The World Health Organisation (WHO).

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