CPhI South East Asia reviews COVID-19 treatments, vaccines and the ASEAN outbreak response

The devastating effects of COVID-19 have been felt globally, with nearly 6 million* reported cases and 360,000* reported deaths worldwide.

So far however, South East Asia has been one of the relatively more successful regions in combatting the disease’s spread, with low case numbers and deaths per million. The region has a combined 86,289* reported cases and 2,644* reported deaths.

To put this into perspective, South East Asia only accounts for 1.5% of global cases, and a mere 0.7% of global deaths. Astonishingly Vietnam, Cambodia and Laos have reported no deaths caused by COVID-19, with Myanmar and Brunei reporting only 6 and 2 deaths, respectively.

The success with which South East Asia has contained COVID-19 is owed in part to the speed at which their governments have implemented strict and effective measures to reduce the infection rate (with R numbers contained to below one).

For example, Singapore was quick to implement a contact-tracing app – TraceTogether – to help individuals keep track of where they may have encountered possible carriers of the virus, responding in real-time with quarantine and isolation. Similarly, Vietnam was quick to implement lockdown measures and even subject overseas visitors to mandatory quarantine at special facilities.

One reason for the pandemic-ready infrastructure is the measures that were put in place after the SARS and MERS breakouts in 2002 and 2012, respectively. But despite how well South East Asia has contained the pandemic via short-term mechanisms, this is not in itself a solution. These economies will now need to gradually resume and their populations will require protection from the ongoing risk.

This ultimately means a viable globally available vaccine and/or approved and efficacious treatment options. To help you understand and digest some of the more than 100 currently active COVID-19 vaccines and the hundreds of trials underway, we have summarised the most promising. These are broken down by subtypes of vaccine approach, drug mode of action, antibodies and convalescents.

*accurate as of 29th May 2020

Regional government responses to COVID-19 outbreak

  • Thailand: declared a state of emergency (March), implemented nationwide lockdown and closure of non-essential businesses and education (April)
  • Malaysia: border closures, travel bans, and nationwide lockdowns implemented (March)
  • Singapore: shut down travel to and from China (February), extensive body temperature testing (February), launched contact-tracing app (March)
  • Vietnam: shut down travel to and from China (February), compulsory body temperature tests at airport arrivals and upon city entry (February), non-essential businesses shut, and 3-week quarantine periods implemented in major regions (February),
  • Indonesia: declared state of emergency (March), closure of all non-essential businesses and schools (March), a temporary ban on entry and transit for foreign travellers (April)
  • Philippines: shut down travel to and from China (February), implemented lockdown on the entire island of Luzon (March), cancellation of Philippine airline flights (March)
  • Cambodia: nationwide closure of educational institutions (March), declared a state of emergency (March), suspended foreign visas (March) 

COVID-19 vaccines in development

Vaccines usually take many years to develop, but the pandemic is forcing innovators to shorten their timelines like never before, and there is hope that a viable COVID-19 vaccine can be developed within 12 to 18 months – with some even targeting approval as soon as Autumn 2020.

Currently, there are over 100 vaccines in development, the majority of which are designed to stimulate the production of neutralising antibodies against the SARS-CoV-2 spike protein. This protein coats the surface of the virus and binds to ACE2 – a protein found on the surface of lung cells – which then facilitates viral entry into the lungs. Below are a few of the most promising and advanced COVID-19 vaccines currently in development.

mRNA-1273 – Moderna Therapeutics (last update: 29th May)

Moderna Therapeutic’s mRNA-1273 is an mRNA that encodes for the SARS-CoV-2 spike protein. The mRNA is delivered to human cells via lipid nanoparticles where the protein will ultimately be produced by the body – this elicits an immune response against the virus, whereby the body will generate antibodies against the spike protein. On May 18th Moderna announced that preliminary data from a 45-person clinical trial conducted by the National Institutes of Health suggested that the vaccine was safe and successfully stimulates the production of antibodies that neutralise SARS-CoV-2 at a medium dose of 100μg. A 600-patient phase II study is due to begin shortly.

CanSino Biologics (last update: 29th May)

CanSino Biologics has developed a COVID-19 vaccine by inserting the spike protein gene into a harmless virus – a genetically engineered adenovirus – which is used to ‘infect’ patients and stimulate antibody production against the spike protein. On May 22nd the company announced that their 108-patient phase I study was a success, with the data suggesting that the vaccine could generate antibodies against the virus in healthy patients.

However, the findings were somewhat underwhelming to some researchers, who believe that the vaccine didn’t stimulate the development of neutralising antibodies (those required to prevent future infection) in a substantial number of patients. The Chinese biotech developed a vaccine using the same technology for the Ebolavirus, which has been approved in China.

INO-4800 – Inovio Pharmaceuticals (last update: 29th May)

Inovio Pharmaceuticals have a number of DNA vaccines in development
– the latest being INO-4800, a vaccine candidate against COVID-19. The company have retrotranscribed the virus’ RNA into DNA and identified the DNA regions that would confer the greatest immunity against the virus using computer simulations. These DNA regions have then been processed into plasmids. Preclinical models suggest that the vaccine generates robust antibodies and T-cell responses against the virus, with preliminary safety and immune response data from a phase I study expected in June.

ChAdOx1 nCoV-19 – The University of Oxford (last update: 1st June)

The University of Oxford has developed the ChAdOx1 nCoV-19 vaccine by inserting the genetic material that encodes the spike protein from SARS CoV-2 into a very weak, non-replicating adenovirus, ChAdOx1. Vaccine administration results in a very mild viral infection, which ultimately stimulates the body to produce an immune response against the spike protein (and therefore SARS-CoV-2) produced by the virus. The vaccine has been found to be safe, with only minor, temporary side effects being shown by some patients, including headaches and a temperature.

Phase I trials for the vaccine began in late April, where over 1,000 healthy volunteers have been immunised, whilst phase II/III trials began in mid-May. The University aims to evaluate the vaccine in a wider age range of participants by including children and older adults, as well as evaluating it in a significantly larger patient population of circa 10,000 healthy adults. On April 30th AstraZeneca announced that they would be partnering with the University of Oxford to help expedite the development, manufacturing and global distribution of the vaccine.

CoronaVac – Sinovac Biotech (last updated: 1st June)

Sinovac Biotech began developing their COVID-19 vaccine candidate - CoronaVac – in collaboration with Chinese academic institutes in January. The vaccine contains chemically inactivated SARS-CoV-2 particles which, when administered to humans, will elicit the production of neutralising antibodies against the virus. Preclinical studies using monkeys yielded extremely positive results regarding the candidate’s safety and efficacy.

In mid-April, Sinovac began a phase I/II placebo-controlled clinical trial in China in to assess the vaccine’s immunogenicity and safety in humans. The company received a combined $15m investment from Advantech Capital and Vivo Capital to advance the development of CoronaVac.

Summary of COVID-19 vaccines in development

Developer

  • Moderna Therapeutics
  • Cansino Biologics
  • Inovio Pharmaceuticals
  • University of Oxford
  • Sinovac

Name

  • mRNA-1273
  • -
  • INO-4800
  • ChAdOx1 nCoV-19
  • CoronaVac

Stage

  • Phase 2
  • Phase 1
  • Phase 1
  • Phase 1
  • Phase 1

COVID-19 treatments in development

A number of drugs have been repurposed with the aim of treating the coronavirus and speeding up recovery times, with numerous clinical trials having already been conducted around the world – albeit, with mixed results. Some of these molecules are broad-spectrum antivirals, whilst others aim to treat the virus’ severe – and potentially fatal – symptoms, such as acute respiratory distress syndrome (ARDS).

Antibody therapies are also in development which, although utilise the same molecules as vaccines to neutralise viruses, serve as a treatment for those infected not as a preventative measure. Below are a few of the most promising and advanced COVID-19 treatments currently in development. 

Remdesivir – Gilead Sciences (last update: 29th May)

Gilead Sciences’ remdesivir is an investigational nucleotide analogue developed to act as an all-purpose antiviral via viral replication inhibition. Gilead used remdesivir in a multi-drug clinical trial for Ebola back in 2015, but it was found to be significantly less effective compared to other tested drugs. However, numerous phase III studies have been conducted in 2020 to test its efficacy at treating COVID-19 and it has shown promise as a drug that can significantly shorten recovery times.

On April 29th the National Institute of Allergy and Infectious Diseases announced that remdesivir lead to a 31% improvement in recovery time from a study of 1000 patients, where patients that took remdesivir recovered after 11 days on average, compared to patients that took a placebo and recovered after 15.

Gimsilumab – Roviant Sciences (last update: 29th May)

Gimsilumab is an investigational anti-inflammatory monoclonal antibody developed by Roviant Sciences. The treatment targets and inhibits GM-CSF - a protein found to be up-regulated in COVID-19 patients and believed to induce ARDS via inflammation. It is thought that inhibition of GM-CSF will reduce the severity of COVID-19 in patients showing symptoms of ARDS. On April 15th Roviant Sciences set up a placebo-controlled trial to test the efficacy of gimsilumab at reducing mortality rates in COVID-19 patients with acute lung injury or ARDS – they hope to enrol up to 270 patients.

MultiStem® – Athersys (last update: 29th May)

MultiStem® is a proprietary stem cell therapy that has been developed by Athersys to treat a range of disease types, including COVID-19-induced ARDS. In early May Athersys announced that they had begun enrolment for a circa 400-patient phase II/III study to evaluate the administration of MultiStem® to treat COVID-19 patients with ARDS.

Celltrion

Celltrion has collaborated with Korea Centers for Disease Control to identify and mass-produce several potent antibodies against SARS-CoV-2 from the blood of recovered patients. On June 1st the company reported positive results from their preclinical studies, whereby their antibody treatment reduced viral load in animal models by 100-fold. Celltrion also reported that the antiviral antibody therapy reversed lung inflammation and shortened recovery times. The South Korean biotech plans on conducting more preclinical studies to further evaluate the therapy’s efficacy and toxicity.

Summary of COVID-19 treatments in development

Developer

  • Gilead Sciences
  • Roviant Sciences
  • Athersys
  • Celltrion

Name

  • Remdesivir
  • Gimsilumab
  • MultiStem®
  • -


Product Class

  • Small molecule
  • Antibody therapy
  • Stem cell therapy
  • Antibody therapy

Stage

  • Phase 3
  • Phase 3
  • Phase 2
  • Preclinical


Convalescent plasma therapy (last update: 1st June)

Convalescent plasma therapy involves taking the blood plasma of individuals who have successfully recovered from COVID-19 and administering it to those currently infected. The aim of the therapy is to deliver neutralising antibodies against SARS-CoV-2 to infected individuals to strengthen their immune response against the virus and expedite recovery time. Although this therapy is effective due to the acquisition of antibodies against the virus, it is not grouped with vaccines as it is not used as a preventative measure.

A number of researchers and doctors from the US are combining their efforts to investigate and assess the potential of convalescent plasma therapy under the ‘National COVID-19 convalescent plasma therapy’ initiative. However, assessing the efficacy of convalescent plasma therapy has proven difficult as patients treated with it are also typically on other antiviral drugs. 

There is no doubt that the COVID-19 pandemic has stimulated innovation and accelerated development timelines like never before. The world is dependent on the development of effective vaccines and treatments in order to restore life back to what it once was. Thanks to global collaborative efforts and investment in research and development, we hope to see these vaccines and treatments available worldwide in under 12 months’ time.

If the pandemic has taught us one thing about the pharmaceutical industry, it is that it is a lot more flexible and adaptable than we previously realised. The exponential progress of these trials will necessitate greater local and regional manufacturing requirements to help meet the needs of patients – with partnering agreements proliferating.

South-East Asian manufacturers should, therefore, continue to monitor developments as we are in a new age of global partnering. Not to mention, localised production of vital and essential medicines in the age of a pandemic will further accelerate opportunities.