Coronavirus Notebook: EU To Buy 30 Million Doses Of Valneva Vaccine, Russia To Issue Compulsory License For Remdesivir

Source : 'The Pink Sheet'

This week the European Commission announced that it had concluded exploratory talks with Valneva SE on an advance purchase agreement for 30 million doses of the French firm’s coronavirus vaccine, with the option to buy a further 30 million.

This is the eighth vaccine the commission is purchasing on behalf of the member states, having already signed contracts with AstraZeneca PLC,Sanofi/GlaxoSmithKline plc, Janssen Pharmaceutica Inc., Pfizer Inc./BioNTech SE, CureVac BV and Moderna, Inc., and concluded exploratory talks with Novavax, Inc. on 17 December. Two of the vaccines, Pfizer/BioNTech’s Comirnaty and Moderna’s mRNA-1273, have been approved in the EU, while a decision on the Oxford/AstraZeneca product is expected on 29 January. ()

Valneva’s VLA2001 is an inactivated virus vaccine, the only one using this approach in clinical trials against COVID-19 in Europe, the commission noted. It said it had decided to support the product “based on a sound scientific assessment, the technology used, the company's experience in vaccine development and its production capacity to supply all EU member states.”

The health commissioner, Stella Kyriakides, said: "With this eighth vaccine, we are adding to our already broad and diversified range of vaccines in our portfolio. By doing this, we can maximize our chances of making sure that all citizens can have access to safe and effective vaccinations by the end of 2021. All member states have now started their vaccination campaigns and will start receiving an increasing number of doses in order to cover all their needs during this year."

Valneva and Oxford Immunotec Global PLC have agreed to use the diagnostics firm’s T-SPOT Discovery SARS-CoV-2 test to determine whether there is a T-cell response in participants in the VLA2001-201 study, a randomized Phase I/II trial evaluating the safety, tolerability and immunogenicity of VLA2001 in about 150 healthy subjects.

The test has shown in previous studies that SARS-CoV-2 responsive T cell numbers were associated with protection from COVID-19, Oxford Immunotec said. “Collecting T cell data in the VLA2001-201 study may add valuable additional information for assessing the efficacy of Valneva’s inactivated whole-virus vaccine candidate.”

The trial, which began in mid-December, is taking place at study sites across the UK. The primary endpoint read-out will be two weeks after completion of the two-dose primary immunization (day 0, 21), Valneva said. “Subject to analysis of this data, including the selection of the optimal dose currently expected in the early second quarter of 2021, additional trials are expected to commence immediately thereafter.”

The company said it planned to include more than 4,000 participants in additional trials, which “could support an initial regulatory approval as soon as the fourth quarter of 2021.”

In Switzerland, the medicines regulator, Swissmedic, has temporarily authorized Moderna’s mRNA-1273 vaccine, noting that “authorization studies have demonstrated a high efficacy rate of 94% 14 days after the second injection of the vaccine.”

The vaccine was evaluated using a rolling review procedure that was “rapid, but at the same time conscientious,” the agency commented. The product information and “official government recommendations” say that the two doses should be given one month apart. “In line with the latest data, Swissmedic recommends keeping to this vaccination interval and not deferring the second dose of the vaccine,” it added, no doubt with an eye to the UK’s controversial decision to delay the second dose of both the Pfizer/BioNTech and AZ vaccines. 

As a condition of authorization, Swissmedic will require Moderna to submit safety, efficacy and quality data on an ongoing basis. It said that authorization applications for other pandemic vaccines would “continue to be processed with high priority in the rolling procedure using all the available resources. Swissmedic will decide on further authorizations of pandemic vaccines as soon as sufficient data become available.”

The Moderna vaccine received a conditional marketing authorization in the EU on 6 January and in the UK on 8 January. The only other vaccine so far authorized in Switzerland is Pfizer/BioNTech's Comirnaty.

Comirnaty was the subject of a hacking attack on the European Medicines Agency last month, during which the EMA said “some documents relating to the regulatory submission” for the vaccine had been unlawfully accessed. ()

In a 12 January update, the agency said the ongoing investigation into the cyberattack had “revealed that some of the unlawfully accessed documents related to COVID-19 medicines and vaccines belonging to third parties have been leaked on the internet. Necessary action is being taken by the law enforcement authorities.”

Sources in the cybersecurity intelligence community told the BleepingComputer website that the leaked stolen data included “email screenshots, EMA peer review comments, Word documents, PDFs, and PowerPoint presentations.”

The EMA stressed that the agency and the EU medicines regulatory network remained “fully functional and timelines related to the evaluation and approval of COVID-19 medicines and vaccines are not affected.”

Sam Curry, chief security officer at cybersecurity firm Cybereason, said “many nation-state actors and other rogue hacking groups” had been involved in efforts to steal vaccine research and disrupt vaccine supply chains since the start of the pandemic. Hackers saw COVID-19 as a “strategically valuable asset and it's likely they will for the foreseeable future.”

Noting that “motivated hackers will be successful every time they attempt to hack a company because they are well funded and are looking to reap both financial and political fame,” Curry said that pharmaceutical and research companies were “working with law enforcement agencies to face these threats head on with advanced cyber tools and improved security hygiene.”

With hacking risks now extending to “mobile, the cloud and other potential attack vectors, those companies that can detect a breach quickly and understand as much as possible about the hacking operation itself will be able to stop the threat and minimize or eliminate the risk all together," he added.

In Australia, the chief medical officer, Paul Kelly, has defended the country’s planned rollout of the Oxford/AstraZeneca vaccine after a group of scientists cited data showing the product had only 62% efficacy and that another vaccine such as those from Pfizer/BioNTech or Moderna should be used instead.

“Until we get more data that shows that AstraZeneca is as good as the others, the scientific and medical risk that you take is that you won’t get herd immunity,” said Andrew Miller, president of the Australian Medical Association in Western Australia.

But in an interview with Sky News, Kelly said that both of the vaccines were sill going through the regulatory approval process and that the Pfizer/BioNTech product could be approved by the end of January and the AZ vaccine in February.

He said that studies showed “the range of efficacy” of the AZ vaccines was “from 62% to 90%,” and the pooled result was 70%. “That well exceeds what the WHO [World Health Organization] sees as the minimum efficacy required for a vaccination,” he declared.

Confidence was “the key here and so I am worried when some people come out strongly in this way with a small amount of information,” Kelly said, adding that the government chose the AZ vaccine on the basis of medical advice. “We've picked our strategy about the priority groups first and who should get that vaccine first on the medical advice. We'll continue to be guided by that medical advice through this year as the vaccine rolls out.”

Professor Andrew Pollard, director of the Oxford Vaccine Group in the UK, said the rollout of the vaccine should not be put on hold over concerns that it might not generate herd immunity, noting that such immunity might never be achieved even with a range of highly effective vaccines, according to the Sydney Morning Herald.

"The debate on efficacy is something which needs to be divorced from the debate on impact," Pollard said. "And impact is what we need if we are going to have societies get back to normal in 2021.”

Russia's Sputnik V vaccine continues to make inroads around the world, having recently received an emergency use authorization in a number of Latin American countries including Argentina, Bolivia and Venezuela, as well as Algeria and Serbia.

On January 13, the Russian Direct Investment Fund (RDIF), which funded development of the vaccine, said that it and the local company, União Química, would apply for emergency use authorization in Brazil this week.

As part of its partnership with União Química, RDIF “actively facilitated the transfer of technology to launch the production of Sputnik V in Brazil, including provision of documents and biomaterials,” the fund said. “Local production of Sputnik V in Brazil has been launched in January.”

União Química plans to supply of 10 million doses of Sputnik V in the first quarter of 2021, with deliveries beginning this month.

Meanwhile, the Russian government has published an ordinance on the issuing of a compulsory license for remdesivir (Veklury) for use in treating patients with COVID-19. The license will allow the Irkutsk-based company Pharmasintez JSC to use the patents owned by Gilead Sciences, Inc. for one year to manufacture the product, according to law firm CMS.

The ordinance was adopted on the basis of Article 1360 of the Russian Civil Code, which provides for the issuing of a compulsory license “in the interests of the defense and security of the state without the consent of the patent holder, subject to notification as soon as possible and payment to the latter of commensurate compensation,” CMS noted.

“Within three months, the Russian Ministry of Industry and Trade must provide the Russian government with information on the payment of commensurate compensation for the use of patents by Pharmasintez JSC to the right holders,” the law firm said.

“Taking into account the lack of a clear definition of ‘state security’ in the legislation, the validity of using the compulsory license mechanism for a pharmaceutical product is controversial. It also raises questions about how the compensation to the right holders will be calculated and to what extent it will correspond to the fair market value of the license.”

Gilead said it was "disappointed by the Russian government's decision to issue a compulsory license for Veklury," as the action was "unnecessary and counterproductive" because Gilead had prices the product "in a way that yields cost savings for governments around the world." The aim of the pricing strategy is to "ensure broad and equitable access to Veklury at a time of urgent global need, and the prices is set at a level that is affordable for upper-middle-income countries with the lowest purchasing power," it told the Pink Sheet.

Gilead said that there was "no evidence of intellectual property as a barrier to access," and that its partnership with JSC Pharmstandard "already lays the local groundwork to pursue the market launch and distribution of Veklury in Russia." It said it hoped Russia would "collaborate with Gilead to ensure that Russians who need Veklury can access it."

CMS added that the Russian state Duma (parliament) is considering a bill that would expand the grounds for issuing compulsory licenses. The bill has been adopted at first reading and must now go through two more readings in the Duma and then be approved by the Federation Council and signed by the Russian president.

The efficacy of COVID-19 vaccines against new variants of the virus is very much in headlines, but the debate is also being had over how effective coronavirus treatments might be against them.

Gilead is now testing remdesivir, which has been approved as Veklury in certain countries for treating COVID-19 patients, to see whether it is effective against the new coronavirus strains that have emerged in the UK and South Africa.

“We fully expect remdesivir to be effective against these strains” because it works in the cell where the virus replicates and “what we know is in these new variants, that part of the cell is not changing at all in fact,” Gilead CEO Daniel O’Day told CNBC this week. He said the company had already tested the substance against more than 2,000 strains in the laboratory setting, and that in each case “it maintains its effectiveness.”

Changes in the makeup of SARS-CoV-2 are also on the radar of the World Health Organization, which convened a one-day meeting this week to discuss “critical knowledge gaps and research priorities for emerging variants of the virus.”

The meeting was held to discuss issues in six specific areas: epidemiology and mathematical modeling, evolutionary biology, animal models, assays and diagnostics, clinical management and therapeutics and vaccines.

“There was a consensus on the importance of integrating the new SARS-CoV-2 variants research into the global research and innovation agenda while enhancing coordination across disciplines,” the WHO commented.

“Our collective goal is to get ahead of the game and have a global mechanism to quickly identify and study variants of concern and understand their implications for disease control efforts,” said Ana Maria Henao Restrepo, head of the WHO’s R&D Blueprint.

So far a total of 350,000 sequences have been publicly shared, but most come from just a handful of countries, the organization noted. “Improving the geographic coverage of sequencing is critical for the world to have eyes and ears on changes to the virus,” said Maria Van Kerkhove, WHO technical lead on COVID-19.

As part of efforts to investigate the origins of the coronavirus pandemic, a WHO team has arrived in the Chinese city of Wuhan, where COVID-19 was first detected in late 2019.

Team leader Peter Ben Embarek told the AFP news agency that it "could be a very long journey before we get a full understanding of what happened. I don't think we will have clear answers after this initial mission, but we will be on the way."

By Ian Schofield