LONDON – The U.K. government has signed a €1.4 billion (US$1.7 billion) advance purchase agreement with French biotech Valneva SE, for the supply of up to 190 million doses of its attenuated COVID-19 vaccine, VLA-2001.

The whole virus product is due to enter phase I/II development in the U.K. in December. Assuming success, phase II/III will start early in 2021, leading to conditional approval and supply of the first 60 million doses in the second half of 2021.

“If we are still in a pandemic setting and the data support conditional approval, there will be commercial supplies next year,” David Lawrence, chief financial officer of Valneva, told BioWorld.

The U.K. then has options to more than 40 million doses in 2022 and a further 30 million to 90 million doses from 2023 – 2025.

As part of the agreement, the U.K. government is helping to fund clinical development. “Trials will be enabled and executed by NIHR [National Institute for Health Research], the same people who already know a lot about COVID-19 trials,” said Lawrence.

The government also is putting in money up front to scale manufacturing for VLA-2001 at Valneva’s facility in Livingston, Scotland, creating around 100 jobs. The investment will be recouped against the vaccine supply.

Lawrence said there currently is one line for VLA-2001 at the facility, which will switch to commercial production in January 2021. That has the capacity to make 15 million doses. The Saint-Herblain, France-based company has acquired a new building where it is installing capacity to manufacture 150 million to 200 million doses, and due to come on stream in July next year. “As the saying goes, having closed the deal, the hard work starts now,” Lawrence said.

At the same time as announcing the U.K. supply agreement, Valneva said it sealed a deal with Dynavax Technology Corp. for commercial supply of its CpG 1018 adjuvant for use with VLA-2001. The adjuvant is expected to boost the generation of neutralizing antibodies and prompt a polarized Th1 immune response.

Despite that, Valneva anticipates VLA-2001 will require a two-dose regimen. However, it is hopeful CpG 1018 will enhance the immune response in older people and immunocompromised groups, who whilst being at greater risk for severe COVID-19 infection are likely to be less responsive to vaccination.

“We think we are going to have a really good safety profile for at-risk groups,” Lawrence said. “We are in pretty good shape to be widely used in certain groups of the population.”

The U.K. government has signed advance purchase agreements for other COVID-19 vaccines based on a range of technology platforms, in hopes of spreading the risk and ensuring at least one effective product is available.

Some of those, such as Astrazeneca plc and Oxford University’s AZD-1222, and Biontech SE and Pfizer Inc.’s BNT-162b2, are further on in development, but Lawrence noted, “There is going to be a need for more than one vaccine.” With the focus on at-risk groups, “we think we’ll be part of the mix,” he said.

VLA-2001 is leveraging the manufacturing technology used in Valneva’s approved Japanese encephalitis vaccine Ixiaro, for which the company won a new $166 million supply contract with the U.S. government earlier this month.

Lawrence said Valneva is in a number of confidential discussions about supplying other governments with VLA-2001. However, there are no plans as yet to run clinical trials outside the U.K. “Our focus is on getting done what we need to do to deliver to the U.K.,” he said.

While the U.K. government has signed other advance purchase agreements for vaccines in development, this is the first time the value of a contract has been disclosed. Other deals are with large pharma companies for which the agreements are not so material; Valneva on the other hand, reported the pandemic had hit its sales in the first half of 2019, with revenues falling to €47.9 million compared to €54.5 million in the same period in 2019. The supply of 60 million doses of VLA-2001 in the second half of 2021 will generate revenues of €470 million

Regeneron antibody cocktail to be tested in U.K. Recovery trial

Also announced on Sept. 14, the U.K. Recovery trial, the largest study of COVID-19 therapies in the world, is to test Regeneron Pharmaceuticals Inc.’s REGN-COV2. The randomized phase III open-label trial will compare the effects of adding the antibody cocktail to standard of care vs. standard of care alone, in patients hospitalized with COVID-19.

The study will assess the impact of REGN-COV2 on all-cause mortality at 28 days. Other endpoints include reduction in hospital stays and the need for ventilation. At least 2,000 patients will be randomly allocated to the REGN-COV2 arm.

REGN-COV2 is the first specifically designed COVID-19 therapy being evaluated by the Recovery trial, which has recruited 12,418 patients. The product was selected based on its emerging safety profile in humans, preclinical data showing it can protect against viral escape mutations, and preclinical research in nonhuman primates showing it reduced the amount of virus and associated damage in the lungs.

Martin Landray, professor of medicine and epidemiology at Oxford University and lead investigator for Recovery, said that while to date Recovery has largely been studying whether existing drugs can be repurposed, it was specifically designed so that as promising new drugs such as REGN-COV2 became available, they can be tested quickly.

“We now have the opportunity to rigorously assess the impact of a drug specifically designed to target this coronavirus … “[That] will provide a robust assessment of the effect of this lab-manufactured monoclonal antibody combination treatment in hospitalized patients,” Landray said.

No Comments