With Bharat Biotech releasing Phase III trial numbers, experts say study does not have key immunological data, raises more questions
The recently submitted final data analysis to DCGI worked out to 77.8 per cent efficacy. Pic/AFP
The good news is that Bharat Biotech's Covaxin safety and efficacy analyses data in trial III has been announced, and the vaccine was found to have 77.8 per cent efficacy and nearly 65 per cent efficacy for the Delta variants. But health care experts differ on this. While some have lauded the outcome of the results, others said that unless appropriate immunological studies are documented, it is impossible to judge the efficacy of any vaccine.
The Covaxin vaccine Phase 3 controlled clinical trial on 25,800 volunteers was conducted in India in 25 hospitals. Although the interim analysis done in March 2021 had shown the overall preventive efficacy at 81 per cent, the recently submitted final data analysis to the DCGI worked out to 77.8 per cent. The vaccine was well tolerated and did not report any serious side effects, including deaths.
ADVERTISEMENT
Covaxin has been evaluated through neutralizing antibody responses against several variants of concern, namely B.1.617.2 (Delta), B.1.617.1 (Kappa), B.1.1.7 (Alpha), B.1.351 (Beta), P2- B.1.1.28 (Gamma). Representation pic/Ashish Raje
“The stratified analysis of the final data reportedly showed that Covaxin’s preventive efficacy was 93.4 per cent towards occurrence of severe Covid-19, and 63.6 percent towards that of asymptomatic infection. It provided almost 65 per cent protection against the Delta variants prevalent in India during the early part of 2021. This possibly did not include Delta-plus variants that started to appear in India in April-May 2021. The latter is not a major lacuna in the Covaxin study, because viral mutations are a dynamic phenomenon and clinical trials do not necessarily track all dynamic occurrences. But it's a welcome step that Bharat Biotech and ICMR have submitted the final reports to the Drugs Controller General of India (DCGI) and the World Health Organisation (WHO), to satisfy monitoring and safety systems," said Dr Subhash Hira, professor of Global Health at the University of Washington-Seattle, and member invited to several WHO Covid review fora. "Although I have not seen the full report, I feel that rapid evaluation of the report leading to the full license of DCGI will be important. That should provide an opportunity to scale up its production for use both, nationally and internationally,” added Dr Hira.
Dr Hira added, “Most developing countries are struggling to get Covid-19 vaccines. A vulnerable country like the Democratic Republic of Congo (DRC) with a population of 90 million people has administered vaccines to 45,000 people. This is despite the fact that its health systems have well-trained vaccinators who successfully injected Ebola vaccines into the entire eastern part of DRC a few years ago. Covaxin's scaled-up production can help deliver the affordable vaccine to the Southern world, without depriving India of supplies.”
However, Dr Wiqar Shaikh, professor of Medicine, Grant Medical College and Sir JJ Group of Hospitals, differed on the study. He said that Bharat Biotech, the makers of Covaxin, have published the results of their Phase 3 trials in a non-peer reviewed journal, medRxiv. Dr Shaikh said, "The paper discussing the results of the Phase 3 trials mentions that the efficacy of Covaxin was 77.8 per cent, and notes the development of IgG antibodies following its administration. But what is surprising is that there is no mention in the study of the more important memory T cells, such as NK cells, and the cytotoxic cells, both of which are extremely significant in providing long-term immunity from Covid-19."
Dr Shaikh quoted a study from the journal Nature in July 2020, in which data was used from patients who suffered from the SARS-CoV1 (SARS) virus in 2003, and which induced a durable memory T-cell response which has lasted for more than 17 years. These memory T-cells also proved to be effective against the current Covid-19 virus (SARS-CoV2).
Dr Shaikh said that medRxiv has published a disclaimer as part of the article that clarifies the nature of the Covaxin study. It said, "This article is a preprint and has not been certified by peer review. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.”
He emphasized that unless appropriate immunological studies are documented, it is impossible to adjudge the efficacy of any vaccine. Immunological data, particularly of memory T cells, is about efficacy against mutant variants such as the Delta variant. Dr Shaikh concluded, "Unless we have robust data on vaccine induced memory T cells, we will need to modify the vaccine against variants, and may not have long-term benefits. Besides, an annual vaccine against Covid-19 may need to be administered as in the case of influenza."
An email was sent to Bharat Biotech seeking comments on Dr Shaikh's remarks, but no reply was received till the time of going to press.
In its official statement on the safety and efficacy of the trial III results, Bharat Biotech's (BBIL) Chairman and Joint Managing Director, Dr Krishna Ella, said, “The safety and efficacy readouts of Covaxin as a result of conducting the largest ever Covid-19 vaccines trials in India establishes the ability of India and developing world countries to focus towards innovation and novel product development. We are proud to state that innovations from India will now be available to protect global populations.”
Covaxin has been specifically designed to meet the needs of global distribution chains, the requirements for which are more critical in low and middle-income countries. It has been formulated to enable shipping and long-term storage at 2-8ºC. It is also formulated to adhere to a multi-dose vial policy, thereby reducing open vial wastage and saving money to procurement agencies and governments alike.
Suchitra Ella, joint managing director, Bharat Biotech, said, “It is a momentous day for everyone, at Bharat Biotech, as we announce the Final Phase-3 results of Covaxin and its efficacy of 77.8%. We wish to thank ICMR, NIV-Pune, Virovax, DSMB and the Adjudication Committee. We earnestly thank our clinical trial sites, principal investigators, IQVIA, and every participant who has reposed their faith in Covaxin.
We sincerely thank all our employees for enduring work pressures through the pandemic and lockdown, with 24x7 commitment amidst unprecedented number of physical challenges, stress and continuous operations. We specially thank our medical affairs team for leading the project, the technical and marketing teams which have relentlessly worked to complete the clinical trials and coordination of 25 sites across the country since May 2020.”
Covaxin has been evaluated through neutralizing antibody responses against several variants of concern, namely B.1.617.2 (Delta), B.1.617.1 (Kappa), B.1.1.7 (Alpha), B.1.351 (Beta), P2- B.1.1.28 (Gamma). The data from these studies has been extensively published in peer reviewed journals and available for review in the public domain.
Prof. (Dr) Balram Bhargava, secretary Department of Health Research & Director General Indian Council of Medical Research, said, “I am delighted to note that Covaxin, developed by ICMR and BBIL under an effective public private partnership, has demonstrated an overall efficacy of 77.8% in India’s largest Covid-19 Phase 3 clinical trial thus far. Our scientists at ICMR and BBIL have worked tirelessly to deliver a truly effective vaccine of highest international standards. Covaxin will not only benefit the Indian citizens but will also immensely contribute to protect the global community against the deadly SARS-CoV-2 virus. I am also pleased to see that Covaxin works well against all variant strains of SARS-CoV-2. The successful development of Covaxin has consolidated the position of Indian academia and industry in the global arena.”
77.8
Percentage of efficacy of Covaxin
Subscribe today by clicking the link and stay updated with the latest news!" Click here!
