Source : 'Scrip Intelligence'
Russian scientists have claimed their COVID-19 vaccine candidate achieved a 92% efficacy rate in its first interim analysis of its Phase III trial, a remarkable result which suggests Sputnik V outperformed Pfizer Inc./BioNTech SE’s vaccine BNT162b2 in data announced just two days earlier.
However, the claims have aroused some skepticism from experts inside and outside the country, who point to the convenient timing and the 2% extra efficacy over Pfizer’s 90% result, which allows Russia’s state-backed researchers to claim their Sputnik V vaccine is superior. Others have defended the scientists but detect political pressure.
Russia became the first to country in the world to approve a COVID-19 vaccine anywhere when its government granted Sputnik V emergency use authorization in August, based solely on Phase I/II study in 76 patients. The authorities proceeded to offer vaccination to thousands of healthcare workers and teachers in September, which some vaccine experts outside Russia saw as reckless in the absence of safety and efficacy data from a larger Phase III trial. Based on the new Phase III data, Russian authorities are now gearing up for a full national vaccination program.
A preliminary analysis of 20 participants with confirmed COVID-19 in the Phase III trial found that the majority were in the placebo group, leading its developers at the Gamaleya National Center of Epidemiology and Microbiology in Moscow to conclude the vaccine had an efficacy rate of 92% after the second dose.
“The publication of the interim results of the post-registration clinical trials that convincingly demonstrate Sputnik V vaccine’s efficacy gives way to mass vaccination in Russia against COVID-19 in the coming weeks,” said Alexander Gintsburg, director of the Gamaleya Center and leader of the research efforts.
“Thanks to the production scale up at new manufacturing sites, Sputnik V vaccine will soon be available for a wider population. This will break the current trend and lead to an eventual decrease in COVID-19 infection rates, first in Russia, then globally.”
The Gamaleya Center held a Zoom press conference on 12 November to present the interim results, which are based on 16,000 participants who have already received both doses of the vaccine candidate.
They claim these early signs show their candidate to be at least a match for Pfizer and BioNTech’s mRNA-based vaccine, but also pledged more interim analyses in the continuing placebo-controlled trial, which has a recruitment target of 40,000 participants.
Phase III trials are also underway in Belarus, the UAE, Venezuela, as well as a Phase II/III study in India. A separate trial of the vaccine’s safety and immunogenicity for elderly people is also being conducted.
Many international experts are not convinced by the interim data, however. Eleanor Riley, professor of immunology and infectious disease, University of Edinburgh, told the Science Media Centre: “Whilst encouraging, I worry that these data have been rushed out on the back of the Pfizer/BioNtech announcement earlier in the week. The Sputnik data are based on only 20 cases of COVID-19 in the trial participants, compared to more than 90 cases in the earlier trial.
“This is not a competition. We need all trials to be a carried out to the highest possible standards and it is particularly important that the pre-set criteria for unblinding the trial data are adhered to avoid cherry picking the data. Anything less than this risks a public loss of trust in all vaccines, which would be a disaster.”
Svetlana Zavidova is executive director of the Association of Clinical Trials Organizations in Moscow. Asked by Scrip if she viewed the trials as reliable, she replied: “Of course not. 20 cases are not enough for such a confident conclusion about 92% of efficacy. We still have no published results of preclinical trials. We still haven’t satisfactory answers to the questions on their publication on Phase II clinical trial results in The Lancet.”
Instead of using a single vector as seen in other adenovirus-based candidates, Sputnik V uses two distinct recombinant adenovirus vectors in a two-dose schedule. The first injection uses Ad26 – similar to that used in Johnson & Johnson’s vaccine. The second injection uses Ad5, similar to the one being employed by China’s CanSino. AstraZeneca’s candidate AZD-1222 uses a chimpanzee adenovirus.
However, results from the Phase I/II trials of Sputnik V published in The Lancet stated that it produced neutralizing antibodies titers lower than those seen in comparable trials of AstraZeneca’s candidate, and the mRNA-based candidates from Pfizer/BioNTech and Moderna.
This makes its apparently high level of efficacy in the new interim analysis more surprising. External experts nevertheless point out that it is impossible to judge the vaccine until more data are generated, and the full results are published in a peer-reviewed journal.
Deputy director of the Gamaleya, Denis Logunov, said further interim analyses would be made when 39 and 78 and 119 cases were reached, with plans to publish the trial protocol and full safety and efficacy data in a peer reviewed journal in December.
However, Logunov did not clarify whether the interim analysis at 20 patients was planned, and did not answer queries on its robustness and statistical significance.
The researchers said the use of the vaccine in 10,000 individuals outside the clinical trials had also generated evidence to supported their 90% plus efficacy claim. They provided no details of how these results were obtained, but did not suggest any trial controls were used.
Russia is not alone in undertaking large-scale vaccinations before generating full safety and efficacy data, as China granted a 12-month authorization to CanSino Biologics Inc.’s vaccine for limited use in its armed forces personnel.
Dr Gillies O’Bryan-Tear, chair, policy and communications, at the UK Faculty of Pharmaceutical Medicine is open-minded about the science behind Sputnik V. He said the world needed many different, safe and efficacious vaccines, based on a range of modalities; some were likely to prove effective in one population group, such as the elderly, where others might work better in younger people.
He rejected the suggestion that the interim data were suspicious, and said: “I'm sorry that's Russia phobia. The Gamaleya Institute is a well-respected vaccine Institute, and they've got very good scientists.”
But he added: “I would say that it's possible that political pressure made them present these result a bit prematurely under pressure, because the Pfizer results came out and that’s a US company.”
Also on the Zoom press conference was Kirill Dmitriev, CEO of the state-owned Russian Direct Investment Fund (RDIF) which is financing the vaccine’s development. Dmitriev has engaged frequently with western media in recent months, defending Russia’s approach and denying accusations of ‘vaccine nationalism’ and that it wanted to see US and European vaccine programs fail.
“We believe that all the different approaches are very important, and that without mRNA [vaccines] succeeding, chimpanzee adenovirus succeeding and inactivated adenovirus succeeding, we cannot move forward.”
He pointed out that Russia has also agreed a deal with AstraZeneca to produce and distribute its vaccine in Russia, should it prove effective and gain approval. Dmitriev also dismissed rumors Russia had been behind cyberhacker attempts to steal COVID-19 research in the west.
“We are not vaccine nationalists. I was just vaccinated with a flu vaccine from France, and, you know, that doesn't make me French,” he said. “We believe that we should just all co-operate, and that Pfizer obviously has a great reputation and a great vaccine and that would be a very important solution for the world.”
Dmitriev also addressed what he called “the elephant in the room” – anti-Russian sentiment in the West, and called on journalists to see beyond it.
“You know there are lots of attacks, some of it comes from honest concerns that are real, some of it comes from misunderstanding…[but] most of it comes from general bias against Russia.”
Zavidova remained unconvinced, however. “The louder their PR, the less trustworthy it is. I prefer trust evidence-based medicine. But in this case we have no evidence, just words and promises.”
RDIF said that it has received requests for more than 1.2 billion doses of Sputnik V vaccine from over 50 countries. It said international partners in India, Brazil, China, South Korea and other countries would help manufacture the vaccine, and able to supply 500 million doses of the Sputnik V outside Russia annually.
By Andrew McConaghie