LONDON – The U.K. Medicines and Healthcare products Agency (MHRA) has given approval for the first-in-human study of Codagenix Inc.’s COVI-VAC, a live, attenuated whole virus COVID-19 vaccine, which is engineered to be structurally identical to wild-type SARS-CoV-2, but is much slower to replicate.

The study will evaluate safety and immunogenicity of intranasally administered COVI-VAC in 48 healthy volunteers, ages 18 to 30, at the quarantine facility in London run by the contract research organization Open Orphan plc.

COVI-VAC is exactly the same as circulating SARS-CoV-2 at the amino acid level, meaning it looks the same as the wild-type virus to the human immune system. It therefore has the potential to induce broad antibody, T-cell and mucosal immunity with a single intranasal dose.

That positions COVI-VAC to be one of the first vaccines to provide long-term immunity from COVID-19, according to Cathal Friel, executive chair of Open Orphan. Volunteers in the phase I “could be contributing to the development of a new breakthrough vaccine candidate that has potential to confer immunity to individuals over a much longer timescale,” Friel said.

The go-ahead for a phase I test of COVI-VAC in volunteers came as the Gamaleya National Center of Epidemiology and Microbiology in Russia announced its Sputnik V vaccine was 91.4% effective at the third and final interim analysis of the ongoing phase III trial.

“The data analysis at the third and final control point of the Sputnik V vaccine clinical trial confirmed the efficacy of the vaccine of over 90%,” said Kirill Dmitriev, CEO of the Russian Direct Investment Fund (RDIF), the sovereign wealth fund that is backing commercialization of Sputnik V. “This is an astonishing, stunning result,” Dmitriev said.

The calculation is based on an analysis of 22,714 volunteers who had received both doses of Sputnik V at the point there were 78 confirmed cases of COVID-19 infection in the trial. Of those, 62 cases were in the placebo arm and 16 in the vaccine group. There were no severe cases of the disease in participants who received Sputnik V, compared to 20 cases in the placebo arm.

“Those cases that were confirmed were mild, with no need for hospital, or any lung symptoms,” Denis Logunov, deputy director of Gamaleya told attendees of a press briefing. “The vaccine provides 100% infection from grave illness,” he said.

Sputnik V has shown greater than 90% efficacy upon reaching 20, 39 and now 78 confirmed cases of COVID-19 infection. Logunov expects the data to improve. “The response will become stronger by day 42; I expect the efficacy to increase,” he said.

The data will now be submitted to a peer review journal and the Gameleya Center will apply for accelerated registration of Sputnik V in a number of countries. Currently, phase III trials are ongoing in Belarus, United Arab Emirates and Venezuela, while a phase II/III is running in India.

RDIF has had requests for more than 2.4 billon doses. The fund has formed partnerships with companies in India, Brazil, China and South Korea to manufacture global supplies.

The vaccine already is approved in Russia, under regulations that allow authorization to be granted on the basis of phase II data at times of national emergency. “I believe we will be able to vaccinate most of the population in Russia in 2021, thereby significantly reducing the scale of the pandemic and creating a strong-long term immunity to coronavirus infection in a significant part of Russia’s population,” said Alexander Gintsburg, director of the Gamaleya Center.

To date, no unexpected adverse events have been seen in the phase III trial of Sputnik V, which uses two different adenoviral vectors to deliver the genetic code for the spike protein by which the virus enters the host cell. Participants will continue to be monitored for at least six months after receiving the first dose of the vaccine.

More vaccines are needed

Farmingdale, N. Y.-based Codagenix has been working with Open Orphan’s Hvivo subsidiary since the end of July to set up the phase I study, which is now expected to start in January 2021, with initial data expected early in the second quarter.

The phase I study was previously slated to start in the fall, and with the first COVID-19 vaccine having received regulatory approvals and others close to market, COVI-VAC could be seen as an also-ran.

However, Sybil Tasker, chief medical officer of Codagenix, said there is likely to be significant unmet need even after the initial roll-out of first generation vaccines. “We believe COVI-VAC, a needle-free single-dose vaccine, is well suited to address potential gaps in supplying the global community,” she said.

The 48 participants in the blinded trial will be split into low-, medium- and high-dose groups, which will be assigned to receive either two doses of COVI-VAC 28 days apart, two doses of placebo, or one dose of COVI-VAC and one of placebo.

“The initial safety and immunogenicity data from healthy adults will position us well to move into larger studies in 2021,” Tasker said.

Codagenix is collaborating with the world’s biggest vaccines manufacturer, Serum Institute of India, in the development and scale-up of COVI-VAC, and production for further clinical trials has begun.

The vaccine grows to high concentrations in standard cell culture, allowing rapid scaling using existing bioprocesses and equipment. The anticipated high immunogenicity implies only modest amounts of active ingredients will be needed to be effective. That will allow production of hundreds of millions of doses per year from existing facilities, according to Codagenix.