Covid-19: Clinical trials bring hope, concerns
At least 100 vaccines are being developed against Sars-CoV-2, which causes Covid-19, with many using new platforms that have not been used in a licensed vaccine before.Updated: May 24, 2020 01:35 IST
Mixed results from clinical trials of several promising treatments and vaccines against the coronavirus disease (Covid-19) released this week brought both cheer and gloom to a world desperate for a safe and effective treatment or vaccine against a disease that has infected at least 5.3 million people and killed 340,000.
At least 100 vaccines are being developed against Sars-CoV-2, which causes Covid-19, with many using new platforms that have not been used in a licensed vaccine before. Vaccines work by training the body’s adaptive immune system to recognise and neutralise invading viruses, bacteria and other pathogens to prevent infection.
In the absence of a treatment or vaccine, one of the major drugs being repurposed to treat this new disease against which humans have no immunity are anti-malarial drugs, hydoxychloroquine and chloroquine, which US President Donald Trump said he has been popping daily to prevent infection.
On Friday, a study of 96,000 hospitalised patients in six continents published in The Lancet journal delivered the disappointing news that those treated with the drug had a significantly higher risk of death compared with those who were not. The drug raised the risk of irregular heart rhythm (arrhythmia) that can lead to sudden cardiac death, concluded the largest analysis on the risks and benefits of treating Covid-19 patients with hydroxychloroquine.
India is the world’s biggest producer of hydroxychloroquine, which is approved for use as a prophylaxis to be given to asymptomatic health workers and contacts of Covid-19 patients since March 23. This was expanded to include frontline workers from May 22.
“Several studies are underway in India, and, as the results emerge, we shall be able to provide more insights into the experiences locally. However, early reports from the pharmacovigilance programme indicate that there are no unexpected spikes of adverse reactions from the use of hydroxychloroquine in the country,” said health minister Dr Harsh Vardhan, in an interview to HT earlier this week.
“As a prophylactic drug, the medicine has shown results in India, which is why it is advised for a larger group now. The Lancet paper that has come out will have implications for treatment regimen, not prophylaxis,” said an official from India’s apex research organisation, the Indian Council of Medical Research, which led a hospital-based retrospective study that found the drug protected healthworkers working on Covid-19 isolation wards from infection.
Remdesivir became the only drug to receive an emergency-use authorisation in the US to treat Covid-19 after early data showed it shortened recovery time from 15 days to 11 days in hospitalised adults with lower respiratory tract infection. A study of 1,063 patients that included 538 who received remdesivir and 521 who were given a placebo showed death in the remdesivir group was 7.1%, compared to 11.9% for the placebo group, but it brought no benefits for severely ill patients on mechanical ventilation, who are at highest risk of death, according to a study published in the New England Journal of Medicine.
“These findings support the use of remdesivir in this population, with the largest benefit observed among individuals who required oxygen supplementation but were not mechanically ventilated. We anticipate that results from our Phase 3 SIMPLE-Severe study [randomised, open-label, multicentric trial to evaluate the safety and efficacy of two dosing durations – 5 days and 10 days – of remdesivir in adults diagnosed with Covid-19], which is evaluating remdesivir in a similar population of Covid-19 patients requiring oxygen but not on mechanical ventilation, will be published in the near future. These data from the SIMPLE-Severe study support treatment of some patients for 5 days rather than 10 days, depending on clinical status,” said the drug’s manufacturer Gilead Sciences, in a statement.
Fewer people get severely ill from Covid-19 in India, and fewer need ventilation support. Of the around 70,000 people currently infected with Covid-19, 2.94% are on oxygen support and 0.45% are on ventilators, according to data from the Union health ministry .
Gilead Sciences has signed non-exclusive voluntary licensing agreements with four generic pharma companies -- Jubilant Life Sciences, Cipla, Hetero Labs, and Mylan – for manufacture and distribution of remdesivir to 127 countries, including India.
The promoters of HT Media Ltd, which publishes Hindustan Times, and Jubilant Life Sciences are closely related. There are, however, no promoter cross-holdings.
Following preclinical animal studies showing Oxford University’s ChAdOx1 nCoV-19 vaccine protected six monkeys from pneumonia, recruitment of around 10,260 adults and children has begun to assess the immune response to the vaccine across ages. The vaccine is made from a weakened version of a common cold adenovirus (ChAdOx1) that causes infection in chimpanzees, and has been genetically changed so it cannot cause infection in humans.
“The Covid-19 vaccine trial team has been working hard on assessing the safety and immunogenicity of ChAdOx1 nCoV-19, and preparing to assess vaccine efficacy. We have had a lot of interest already from people over the age of 55 years who were not eligible to take part in the Phase I study, and we will now be able to include older age groups to continue the vaccine assessment,” said Sarah Gilbert, professor of vaccinology at the Jenner Institute at Oxford University, on Friday.
Oxford University has licensed the experimental vaccine to AstraZeneca, with who the Pune-based Serum Institute of India (SII) is in talks about mass production. “Our discussion with AstraZeneca is ongoing and we can comment further once the deal is concluded. However, we can certainly say that we will be able to provide them with more than 100 million doses,” said an SII spokesperson.
Sino Biotech vaccine
Sino Biotech’s inactivated Ad5-vectored Covid-19 vaccine is among at least seven such where teams are using traditional platforms to develop vaccines using a weakened or inactivated form of the virus, such as those used in measles and polio vaccines. The Sino Biotech vaccine was found to be safe, well tolerated, and able to generate an immune response against Sars-CoV-2 in humans, according to new research published in The Lancet.
The Ad5 vectored COVID-19 vaccine is the first vaccine to be tested in humans and demonstrated a strong immune response after 28 days in 108 healthy adults. The final results will be evaluated in six months after there is data about how effective and long-lasting the protection is against SARS-CoV-2 infection. If successful, the vaccine will be produced in China and, as of now, India has no role in its development and production.
Moderna announced earlier this week that its experimental vaccine mRNA-1273 produced virus-neutralising antibodies at levels similar to those found in recovered patients. It said early data showed the vaccine raised the levels of neutralising antibodies in eight vaccinated people to levels found in the convalescent plasma of recovered patients.
The vaccine is the most advanced among at least 20 experimental nucleic acid vaccines against Covid-19 in various stages of clinical development that use the messenger RNA (mRNA) platform to elicit an immune response against Sars-CoV-2, according to the World Health Organization (WHO)’s draft landscape of Covid-19 candidate vaccines. If it is approved, it will be the first messenger RNA (mRNA) vaccine against any disease in the world.
The US-based company, however, is drawing flak for not publishing data in a peer-reviewed medical journal. Moderna has developed the vaccine in partnership with US National Institute for Allergy and Infectious Diseases, which is expected to publish the data .
Moderna has never brought a vaccine to market, though it has several vaccines in the pipeline.
“This is not the most advanced mRNA vaccine being developed by Moderna, they have started others much earlier. Some are more advanced in terms of actual development (phase 2) but none are approved so far,” said Dr Anurag Agrawal, director, Council of Scientific and Industrial Research-Institute of Genomics & Integrative Biology, New Delhi.