 "coronavirus")
Hyderabad-based Bharat Biotech International (BBIL) had changed the dosage from 3 micrograms of antigen to 6 micrograms during its Covid-19 vaccine trial, a point that the subject expert committee (SEC) would closely examine when it meets on Wednesday to review its application for an emergency use authorisation (EUA) for Covaxin.
The panel would also review the applications of Pfizer-BioNTech and Serum Institute of India (SII) seeking an EUA for their vaccines.
While many have raised questions over BBIL applying for an EUA during an ongoing efficacy trial, the Indian Council of Medical Research (ICMR), the country’s apex health research institute, has defended the move.
ICMR Director General Balram Bhargava said that in the case of temporary licensure or emergency use, the regulator had to be satisfied with the risk-benefit ratio. “In this emergency situation, if the benefit is more, then it may be considered. Numbers are there — from phase 1, we get the safety data. And from phase 1 and 2, we get safety-immunogencity data.”
He added that this data was available for many vaccines covering a period of several months. “These numbers are available for different vaccines, on a very small number of participants...the risk-benefit is the most important thing to look at in a pandemic situation, but ultimately the national regulatory authority has to take the decision.” At least two experts working closely with the regulator on this process said that in a risk-benefit analysis during a pandemic, one had to first look at the safety parameters of the candidate, and then evaluate its efficacy.
“Several points would be discussed in tomorrow’s meeting —for one, BBIL had changed its dosage during the trial. It had come to seek approval for the same. We will be reviewing this bit very carefully,” said one person in the know.
BBIL now has at least two distinct arms of their earlier phase trials — one where participants were given two doses 3-microgram antigen, and one where they were given two doses of 6 micrograms. Altering a dosage can change the results for immunogenicity, something that experts would review. As for the efficacy data, people in the know said the company had submitted the data from phase 1 and phase 2, and not yet submitted the data from phase 3 trials, which are underway.
BBIL refused to comment on the matter, but said it would disclose the data once it completes the phase 3 trials.
According to some reports, BBIL expects to have 130 positive cases of Covid-19 in their efficacy trial. The trials are designed keeping in mind the endemicity of the disease in the area. The company may unblind the data (who got the vaccine and who got placebo) once around one-third or two-thirds of this number is reached. BBIL did not confirm this.
As for the other applicants, Pfizer-BioNTech has done a global trial on over 43,000 people and they do not have an Indian arm. An expert said it would be important to look at the data from people of Indian origin. “It is important to have data on the Indian demographics. We will definitely evaluate this point,” said the source. Pfizer-BioNTech has not yet applied for conducting clinical trials in India.
SII has done its phase 3 trial on 1,600 Indian volunteers to check the safety and immunogenicity of the AstraZeneca-Oxford vaccine candidate, Covishield. The Indian regulator is likely to discuss the matter with its counterpart in the UK to arrive at a decision, sources said.
AstraZeneca is yet to submit data from the UK arm to the Indian regulator, and will do so this month.
As experts meet on Wednesday, they are likely to evaluate which case has more merits for an urgent approval. “Meetings stretch for hours, at times eight to 11 hours as data is analysed in-depth. If not satisfactory, the SEC would not give its nod to any candidate,” said a source.
