Emergency use of vaccine is based on safety, immunogenicity data, says ICMR chief

By Priyanka Sharma
New Delhi [India], January 5 : The Indian Council of Medical Research (ICMR) director Dr Balram Bhargava on Tuesday said that in a pandemic situation, restricted emergency use of the vaccine is considered based on phase 2 safety and immunogenicity clinical trial data while phase three clinical trials are still ongoing.
Soon after the Drugs Controller General of India (DCGI) on Sunday announced "restricted emergency use" for two COVID-19 vaccine candidates-- Bharat Biotech's Covaxin and Serum Institute of India's Covishield-- some people in the scientific and political community started to raise doubts on the safety and efficacy of the indigenously developed Covaxin.
Dr Bhargava informed about the new drugs and clinical trial rules which are pre-Covid issued on March 19, 2019, of which page 186 to 187 clearly says-- "If the remarkable efficacy is observed with a defined dose in phase II clinical trial of investigation new drug unmet medical needs of serious life-threatening diseases in the country, it may be considered for grant of marketing approval by Central licensing authority based on phase 2 clinical trial."
The World Health Organisation (WHO) has three criteria for the approval of the vaccine. They include safety, immunogenicity and efficacy. However, under emergency circumstances like COVID19 pandemic, in the large public health interest, the global health agency has fixed minimum criteria that the efficacy data should meet at least 50 per cent.
"The existing pandemic situation with high mortality, available science and lack of definite and treatments are considered by Subject Expert Committee (SEC) for accelerated approval that is in our legal provision," Dr Bhargava said.
In a pandemic situation, restricted use is considered based on safety and immunogenicity phase 2 clinical trial data while phase 3 is still ongoing, he said adding that "Immunogenicity data generated through phase 2 clinical trial serves as a surrogate for efficacy and the clinical trial rule 2019. The CTR provides for considering phase 2 results to guide approval."
He further said, "SEC guides the DCGI in the process of decision making for restricted use under emergency situation. So, now we have these two vaccines--Covishield and Covaxin."
"One is inactivated the whole virion and the inventors are Bharat Biotech and Indian Council of Medical Research and Bharat Biotech has licensing rights. While the other Covishield vaccine is a recombinant vectored vaccine expressing spike protein. The inventors are Jenner Institute and Oxford University while the AstraZeneca and Serum Institute of India have licensing rights," he said.
Further talking about the Covisheild vaccine, ICMR director said, "In Covishield, we have the UK studies in animals which showed that pneumonia is prevented in monkeys and they have elicited good immunogenicity response in mice. The clinical trials phase 1 and 2 in 1,077 participants showed an acceptable safety profile and homologous boosting increased antibody response. The phase 2/3 in prime regimen in 560 participants is better tolerated in older adults than in younger adults and has similar immunogenicity across all age groups after a boost dose."
While phase 3 in 11,636 participants from UK and Brazil showed that with two standard doses, vaccine efficacy was 62.1 per cent, Dr Bhargava said.
He added that the low dose which was followed by a standard dose, showed the efficacy of 90 per cent and overall vaccine efficacy was 70.4 per cent.
In terms of Indian phase 2/3 studies about Covishield, he said that "There were 1,600 participants who were recruited above 18 years of age. Their immunogenicity data is being generated and more than half is available. Covishield is safe and immunogenic and data showed that it is non-inferior to UK product."
Covaxin's Indian studies on animals like rats, mice, rabbits, hamsters and monkeys showed excellent safety, immunogenicity and robust viral clearance, ICMR director added.
"Phase 1 and 2 clinical trials on 375 and 380 (18-55 and 12-65 years) participants revealed very low adverse events. It showed neutralising antibody response equivalent to human convalescent serum, strong antibody response to all structural proteins (spike, RBD, and N protein), CD4-T cell response, CD45 RO T cell memory response (3 months after vaccination). Th1 biased cytokine response," he said.
On the issue of phase three trial, Dr Bhargava said, "The Phase 3 clinical trial about 25,800 participants is the target and 24,000 enrolled so far. No safety concerns and restricted use in clinical trial mode with consent and follow-up."
"These are the publications of the Covaxin-- The animal studies have been published in Nature Communications and High Science which is a cell journal. The phase 1 trial has been published in Lancet in infection disease appearing in a press on January 8 and the phase II paper is under review and they also have the protocol of phase 3 which is also under review by the British Medical Journal," he added.
There is another important publication in the Indian Journal of Medical Research which has compared the large animal data in all the vaccine products and shown the efficacy of this as well, ICMR director said.