Singapore’s search for a cure and vaccine for COVID-19

SINGAPORE — Covid-19 arrived in Singapore on Jan 23.

There are over 30,000 people here infected with the virus, while the global total has surpassed five million, with more than 330,000 deaths.

One reason for the quick spread and high fatality is that this is a novel virus and anyone who encounters it would not have developed prior immunity.

The elderly are particularly vulnerable, with high death rates observed in nursing homes in many parts of the world.

Public health and social distancing measures work to contain and limit the spread of the virus.

However, to deal decisively with Covid-19, there is an urgent need for two items in the doctor’s inventory.

First, a vaccine to immunize enough people in the population to prevent further propagation of the virus.

Second, an effective and safe cure to treat patients with serious illness and complications from the disease.

As the Sars-CoV-2 virus that causes the disease was not previously known to doctors and scientists, both vaccine and cure do not exist today. It also does not help that it typically takes many years, sometimes up to a decade, to develop a new drug or vaccine.

In Singapore, we have strengths across our hospitals, universities and research institutes to study how the virus behaves and causes disease as well as how infected patients mount immune responses against it, and to develop new technologies to detect, track and neutralize the virus.

When the outbreak of a new atypical pneumonia first emerged in Wuhan, China, the National Centre for Infectious Diseases (NCID) was quick to bring together experts from across Singapore to collectively tackle the challenges posed by this virus.

Repurposing existing drugs

Developing a cure for a novel virus from scratch may take too long.

So, the first approach was to find out if any existing drugs work against it.

A repurposed drug must have data to show its effectiveness in the laboratory and in animals, and an acceptable safety profile.

There were lessons that could be learnt from drugs tested against other coronaviruses that cause the severe acute respiratory syndrome and Middle East respiratory syndrome, as well as other infectious diseases.

The NCID research group systematically combed the medical and scientific literature for potential drugs that could work against Covid-19.

Early candidates were chloroquine and hydroxychloroquine, which are used to treat malaria and inflammatory diseases such as lupus and rheumatoid arthritis.

While the early data was promising, this was subsequently shown to work poorly against the disease.

Another drug, Kaletra (lopinavir-ritonavir), was used against the human immunodeficiency virus that causes Aids. Our experience was that the drug had poor efficacy against Covid-19 and gave rise to many side effects.

This was subsequently shown to be ineffective from clinical trials conducted in other countries.

We also learnt of an experimental drug, remdesivir, which was developed against Ebola. The company that developed it, Gilead, was planning to start clinical trials in the United States and other countries.

Within four weeks of our first meeting with Gilead, NCID and other Singapore hospitals were able to start recruiting patients for clinical trials involving remdesivir.

This was facilitated by rapid approvals from medical, regulatory and ethics bodies here.

Singapore also participated in a multi-country trial led by the US National Institute of Allergy and Infectious Diseases (NIAID), which was important as it compared remdesivir with a placebo.

On April 29, Dr Anthony Fauci, director of NIAID, announced that remdesivir significantly improved recovery of Covid-19 patients.

What was amazing was the complete enrolment of 1,063 patients internationally in less than 60 days.

While there has been a proliferation of more than 300 clinical trials for Covid-19, it was important for NCID to be very selective in evaluating which ones to participate in.

The evaluation had to consider the scientific and clinical evidence, as well as the design of the clinical trial.

By working with Gilead and NIAID, Singapore was able to enrol close to 100 patients in the remdesivir trials.

Harvesting and engineering antibodies

Another approach was to harvest antibodies from Covid-19 patients to treat others with the disease.

This use of convalescent plasma has been shown to work in other serious virus infections.

However, the quantity of antibodies that can be recovered is limited, and it will be challenging to produce enough quantities to treat more than a few individuals.

To overcome this limitation, a number of biotech companies have established platforms to scale up the production of antibodies against Covid-19.

One such company, Regeneron, has produced an antibody cocktail that has been shown to be effective in the laboratory.

Through an agreement with NCID, blood samples from recovered Covid-19 patients from Singapore contributed towards pre-clinical research and development of this cocktail.

We have also initiated talks for Singapore to potentially participate in clinical trials planned for the coming months.

A number of Singapore groups have also joined the international race to develop monoclonal antibodies against Covid-19.

Monoclonal antibodies are immune system proteins that are created in the laboratory.

These include local biotech company Tychan, as well as a partnership between the Agency for Science, Technology and Research’s Singapore Immunology Network and pharmaceutical company Chugai.

Monoclonal antibodies can be specially designed and engineered to target the Sars-CoV-2 virus.

The advantage is that these can be developed over several months, they can be produced in large batches and a single injection may last for a few weeks.

There are plans for clinical trials to be conducted here and, if successful, the possibility to localise manufacturing as well.

Developing a vaccine

Today, there are over 100 vaccine candidates being developed by biotech and pharmaceutical companies, some with the support of international coalitions.

These include traditional vaccine technologies using inactivated or live attenuated viruses (which have been weakened or altered so they do not cause illness), which are time-consuming and require considerable resources to make.

What is also exciting are nucleic acid vaccines (for example, RNA or DNA) synthesized using genetic materials from the virus.

With modern biotechnology, such vaccines can be manufactured in large quantities and, as they are generally required in only very small doses, provide an approach to producing the billions of doses required to vaccinate people around the world.

While Singapore has limited expertise to develop its own Covid-19 vaccine, it has actively engaged leading vaccine groups and companies internationally.

The goals are for Singapore to participate in vaccine clinical trials, as well as to expedite regulatory review and approval for any successful vaccine.

The Duke-NUS Medical School, for example, is working with Arcturus Therapeutics on its RNA vaccine, which has been shown to be highly effective in pre-clinical studies.

Singapore has also registered to be a trial site for the World Health Organization’s adaptive multi-country Solidarity vaccine trials.

Covid-19 has caused societal and economic disruptions globally, and has taken a significant toll on human lives.

Only a cure or treatment can bring an end to this pandemic.

Singapore will continue to work closely with groups around the world in these efforts, and to ensure its timely access to successful drugs and vaccines.