Serum Institute of India (SII) may have to conduct additional tests for approvals to market a version of ‘Covishield’ in India that could be more effective at preventing symptomatic Covid-19 cases than it possibly might be at present, The Indian Express has learnt.
This stems from preliminary findings this week that AstraZeneca and University of Oxford’s AZD1222–the vaccine on which Covishield is based–had an efficacy of 90 percent when participants were given half a dose first, followed by a full-dose booster shot a month later. By contrast, it had an efficacy of only 62 percent when given to other participants as two full doses nearly a month apart.
In India, Covishield is being administered to around 1,600 participants as two full doses 28 days apart, said a senior government official privy to the design of SII’s phase 2/3 clinical trial.
The Pune-headquartered firm’s founder, Dr Cyrus Poonawalla, told The Indian Express on Monday that it would be asking the Central Drugs Standard Control Organisation (CDSCO) for “special emergency marketing authorisation” for Covishield in 45 days.
Given that SII only sought permission to test the full dose-full dose regimen in India, it can only seek permission to administer the vaccine as two full doses nearly a month apart, according to the official cited earlier.
“What has been approved (for testing) is the full dose only…they (SII) have to ask for (emergency use authorisation) for the full dose regimen only,” the official told The Indian Express on condition of anonymity.
“If they will ask for (marketing) permission for half dose, they will have to conduct trials for half dose as well,” the official said.
At the same time, the testing for this additional dosing regimen may not have to be as drawn out as they could apply to CDSCO to include this as a “separate arm” in the ongoing trials of Covishield in India, according to the official. This may mean that the number of participants they would have to recruit for this arm can be reduced and the firm can do a phase 3 trial for this regimen directly, the official said.
“If they’re using only the full dose-full dose regimen, it is likely that Covishield may come out with a similar efficacy readout of around 60 percent. This would still be enough for them (SII) to apply for approvals from the Indian drug regulator, because its guidelines suggest that a vaccine has to meet an efficacy of around 30 to 50 percent for a Covid-19 vaccine to receive approval,” Massachusetts-based vaccine expert Dr Davinder Gill earlier told The Indian Express.
“Right now, a lower efficacy of 60-70 percent may not be a big issue, because India doesn’t have a Covid-19 vaccine yet. But, a year from now, when multiple vaccines have been approved, then a 15-20 percent difference in efficacy will matter,” he added.
SII declined to respond to queries emailed on November 24 about whether it would seek approval to market a dosing regimen that included administering half a dose of Covishield followed by a full dose 28 days later. It also declined to respond to a query about whether it would seek permissions from CDSCO to conduct additional tests using this regimen.
Emailed queries on November 24 and repeated phone calls and messages to Drug Controller General of India Dr VG Somani, the chief of CDSCO, on November 25 also remained unanswered by press time Wednesday.
“We see a lot of merit in this regimen and we will now start discussions with regulators into incorporating this dose combination for further clinical investigation,” an AstraZeneca spokesperson told The Indian Express.
“Our agreement with Serum Institute of India (SII) is a key part of our efforts to bring AZD1222 to low- and middle-income countries and beyond. The licensing agreement with SII is to supply one billion doses for low- and middle-income countries,” the company’s spokesperson added.
AZD1222’s average efficacy, combining the two separate dosing regimens, was pegged at around 70 percent. The vaccine was termed “highly” effective, as it was proving an ability to prevent “severe” disease and hospitalisation among those inoculated, according to Dr Andrew Pollard, director of the Oxford Vaccine Group and the lead investigator of the AZD1222 trial in the UK.
The 90 percent efficacy, announced on Monday by AstraZeneca and The University of Oxford, came from an analysis of 2,741 participants enrolled in the UK arm of AZD1222’s global trial.
Participants in other countries were not on the regimen that included the half dose, as the dosing in the UK that led to the higher efficacy readout was accidental in nature, as per a Reuters report.
However, AstraZeneca is already considering approaching the US Food and Drug Administration (US FDA) for permission to try the lower dosing regimen in participants in the American arm of AZD1222’s global trials.
“Obviously, we will need to take the regulators–the FDA–through the data we have so far, but our plans would be–assuming we get their okay–to incorporate another arm into the study that would test the half dose-full dose regimen as well, and we would set that up within weeks, we hope,” said Mene Pangalos, Executive Vice President for Biopharmaceuticals R&D, AstraZeneca on Monday during a media briefing after the Swedish-British firm and The University of Oxford released information related to AZD1222’s efficacy.
Over 11,000 participants in the US have been dosed with AZD1222 so far.
“We think that, by giving a smaller first dose, we’re priming the immune system differently. We’re setting it up better to respond, and what we don’t know at this moment is whether that difference is in the quality or the quantity of the immune response, and that’s something we’re going to be digging into over the next (few) weeks,” said Dr Pollard during the briefing on Monday.
“It’s still a reasonable amount of the population–it’s about a third of those (participants) in the UK (arm of the trial). The confidence around that estimate (90 percent efficacy) is quite high…more data would provide even greater confidence in that,” he said, adding that more information was being accumulated to substantiate these preliminary findings.x
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