Bharat Biotech's Covaxin Safe, Phase 3 Trial Data Shows 77.8% Efficacy Against Symptomatic Covid: Lancet

BBV152 COVID-19 Vaccine: Findings published in The Lancet indicate Covaxin induces robust antibody response. No severe vaccine-related adverse events or deaths reported among trial participants.

File image of a healthcare worker holding a vial containing doses of Covaxin, manufactured by Bharat Biotech, at a vaccination centre in New Delhi | Photo: Getty

New Delhi: Between November 2020 and May 2021, randomised controlled trials were conducted among participants aged 18 to 97 in India to determine the efficacy of Bharat Biotech's Covaxin (BBV152) Covid-19 vaccine. An interim analysis of the Phase III controlled trials shows that two doses of the BBV152 vaccine provide 77.8 per cent protection against symptomatic Covid-19, two weeks after receiving the second dose. 

The findings have been recently published in the journal Lancet.

A phase III clinical trial is a study that tests the safety and efficacy of a new treatment compared with a standard treatment.

The Lancet study states that a robust antibody response is induced by Bharat Biotech's Covaxin. The trial participants showed no signs of severe vaccine-related adverse events or deaths. The only reported incidences of adverse events are those of headaches, fatigue, fever and pain at the region where the vaccine is injected. However, these were mild, and occured within seven days of vaccination, the report mentioned.

BBV152 — India's First Indigenous Covid Vaccine

Whole-Virion Inactivated SARS-CoV-2 Vaccine or BBV152, is India's first indigenous, whole-virion, inactivated vaccine developed by Bharat Biotech in collaboration with the Indian Medical Research Council (ICMR) and the National Institute of Virology (NIV) for the treatment of Covid-19. BBV152, the research name for Covaxin, recently received emergency use approval from the World Health Organization (WHO) for people aged 18 and older.

It is Vero cell derived, which means it is obtained from vero cells from the kidney of an African green monkey. The fact that it is an inactivated whole virion vaccine means that it contains viruses whose genetic material has been destroyed by heat, chemicals or radiation, so that they cause no disease, but provide a good immune response. 

BBV152 is formulated with a novel Algel+IMDG adjuvant, and must be administered in two doses, with a gap of 28 days between them. The optimum temperature range for storage and transport of the vaccine is 2 to 8 degrees Celsius.

Findings Of The Phase 3 Trials

As many as 25,797 participants were involved in the trial conducted between November 16 and May 17. Out of these, 24,419 adults were randomly administered either two doses of the vaccine, or a placebo, which is an inactive drug or treatment used in a clinical trial. As many as 12,221 participants belonged to the vaccinated group, while 12,198 were part of the placebo group. The study, funded by Bharat Biotech International Limited and the Indian Council of Medical Research, was conducted across 25 hospitals in India. 

Laboratory-confirmed (RT-PCR positive) symptomatic Covid-19 was observed in some participants. The onset of the disease took place at least 14 days after receiving the second dose.

As many as 16,973 participants were initially seronegative (showing negative result for the presence of SARS-CoV-2 antibody in the blood), 130 of whom subsequently became RT-PCR positive, indicating symptomatic Covid-19. 

As many as 24 positive cases were recorded among 8,471 people in the vaccine group, and 106 positive cases among 8,502 people in the placebo group. An efficacy analysis suggests an overall vaccine efficacy of 77.8 per cent, mentions the study. 

In the efficacy analysis population, which consisted of 130 participants, 16 people suffered from severe symptomatic Covid-19 disease. One person belonged to the vaccine group, while 15 persons belonged to the placebo group. The symptoms include severe systemic illness, respiratory failure, evidence of shock or significant acute renal, hepatic, or neurologic dysfunction. 

The authors noted, however, that further research must be conducted with a larger sample to determine the efficacy of the vaccine against severe disease and hospitalisation, according to a Lancet statement.

The study states that the trial participants showed a good response to BBV152. An adverse event was reported in only 12 per cent of the participants in both the groups. Also, there were no cases of anaphylaxis (acute allergic reaction to an antigen), or vaccine-related deaths. 

The researchers analysed the immune response induced by BBV152. They observed a strong neutralising antibody (antibody responsible for defending cells from pathogens) response on Day 56, which is one month after receiving the second dose. 

When the neutralisation activity of the vaccine in Phases I and II of the controlled trials was compared with that in Phase III, it was observed that the neutralisation activity against the Alpha variant remained almost the same. However, there was a marginal reduction in neutralisation activity against other variants of SARS-CoV-2 such as the Delta and Gamma variants, the study found.

A preliminary analysis (initial process at the start of a project that determines whether the concept is viable) of the efficacy of BBV152 against the Delta variant was conducted, and an efficacy of 65 per cent was observed. The scientists clarify that the data is preliminary, and further observations are necessary to confirm the clinical efficacy of the vaccine against Delta and other variants, mentions the Lancet statement.

No significant differences in immune responses were observed across the broad age groups. 

However, the study has some limitations, the authors noted. For instance, the researchers were unable to calculate vaccine efficacy after a single dose as a low number of cases were reported between the first and second doses. Also, the data on efficacy of the vaccine against variants other than Alpha and Delta has been presented as preliminary, and the study population is limited only to India.

It was originally planned that the study participants will be monitored for one year after the second dose. However, considering the situation of the Covid-19 pandemic in India, and the fact that BBV152 has received emergency use authorisation from WHO, the Data and Safety Monitoring Board (DSMB), and the researchers of the study, came up with the decision to un-blind the placebo participants, who were eligible to receive an approved Covid-19 vaccine.