Days after Pfizer revealed the first interim Phase 3 trial data for any COVID-19 vaccine, Russian authorities have announced their vaccine candidate is also demonstrating promising results. Experts are calling the Russian data encouraging, but also caution the results are premature and based on very low numbers.
Russia, like many countries, has been rapidly working on its own COVID-19 vaccine. Called Sputnik V, the vaccine controversially made international news months ago after Russian President Vladimir Putin granted it regulatory approval before Phase 3 trials even started.
Unlike the Pfizer vaccine, which leverages a still experimental mRNA technology, Sputnik V is a much more traditionally designed vaccine. It uses a harmless engineered adenovirus to help the immune system recognize the protein SARS-CoV-2 uses to infect cells.
Adenovirus-based vaccines are not new, and have a well-established safety profile. However, because these innocuous adenoviruses are relatively common, questions have been raised over whether they are too familiar to many immune systems.
Russia’s Sputnik V vaccine attempts to get around the adenovirus familiarity problem by utilizing two different engineered adenoviruses. Administered several weeks apart, the plan is that even if the immune system recognizes the adenovirus in the first shot, it shouldn’t be too familiar with the virus in the second.
A press release recently issued by the Russia’s National Research Center for Epidemiology and Microbiology is offering up the first look at Phase 3 trial data for Sputnik V. The announcement notes that while 40,000 participants have been enrolled in the ongoing trial, only 16,000 have progressed far enough to be included in this interim analysis.
Generally, final phase vaccine trials work by enrolling large volumes of subjects who are blindly and randomly split into either placebo or active groups. Once a certain amount of confirmed infections are detected in the entire cohort a review board analyses the data.
The previously announced Pfizer vaccine data, from a trial encompassing around 40,000 subjects, was based on 94 confirmed COVID-19 cases. Its original threshold for an interim review was raised from 32 cases to 62 after FDA discussions in October. So for Pfizer to claim its vaccine is over 90 percent effective it would mean less than 10 of those confirmed COVID-19 cases were in the active vaccine group.
In this new Sputnik V announcement, researchers are claiming the adenovirus vaccine is 92 percent effective. This is based on only 20 confirmed COVID-19 cases from a cohort of 16,000, much less than thresholds needed to trigger interim analyses in other COVID-19 vaccine trials.
Eleanor Riley, an infectious disease specialist from the University of Edinburgh, suggests the data is encouraging but she worries it has been rushed out to compete with the recent Pfizer announcement.
“This is not a competition,” says Riley. “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.”
Most experts agree this Sputnik V announcement is certainly premature, and there are inarguably plenty of unanswered questions, such as whether the vaccine is preventing infection or merely protecting from severe disease. But taken on its merits, the data appears to be a promising indication that other vaccines in development may also work against SARS-CoV-2.
“… these early results are consistent with the results of the Pfizer vaccine and so this is good news not just for the Sputnik 5 vaccine but for other vaccines in development,” says Paul Hunter, from the University of East Anglia. “If the first two very different vaccines are producing about 90 percent effective then it does suggest that several effective vaccines will reach market in the coming months and if other vaccines are more stable then it will be easier to distribute them including into low income countries.”
Charles Bangham, from Imperial College London, calls these preliminary results reassuring but notes there are pros and cons to this kind of adenovirus-based vaccine strategy. A particular advantage to this type of vaccine is it does not require the degree of ultra-cold storage needed to protect mRNA vaccines. This would allow for easier distribution throughout countries unable to easily manage ultra-cold chain supply lines.
“The Sputnik V strategy has some advantages, notably the less stringent need for cold storage, but the adenoviruses used are also likely to produce more side-effects such as fever or headache – although these are expected to be mild,” says Bangham. “However, proper evaluation of the safety and efficacy of each of these two vaccines, the duration of protection, and their effectiveness in the elderly, must await publication of the full data on the trials.”
The Phase 3 Sputnik-V trials are ongoing, and researchers claim all data will ultimately be published in peer-reviewed journals. Alexander Gintsburg, director of the Gamaleya Center, strikingly suggests mass vaccination in Russia could begin in the next few weeks.
“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,” says Gintsburg. “Thanks to the production scale up at new manufacturing sites, Sputnik V vaccine will soon be available for a wider population.”
