The French company’s COVID-19 vaccine development had previously been underpinned by a development, manufacturing and supply contract with the UK Government worth €1.4bn ($1.65bn) over five years: but in September the UK cancelled the contract over a alleged breach of supply agreement obligations (accusations which Valneva ‘strenuously denies’).
Pivoting its efforts, the company has now secured a supply agreement with the EU, with authorization and distribution potentially happening as early as the first quarter of next year.
EU supply agreement helps fill hole left after UK cancellation
Valneva had originally been set to supply the UK with up to 190 million doses between 2021 and 2025 (with an initial 60 million doses plus option for more).
The deal with the European Commission, announced at the end of last month, will now see it supply up to 60 million doses to the EU over two years.
Of this, 24.3 million doses are expected to arrive during the second and third quarters of 2022, subject to the authorization of the vaccine by the EMA. The European Commission then has the option to increase the initial purchase order to up to 60 million doses, in which case the remainder would be delivered in 2023.
Valneva has already started manufacturing for the European Commission supply contract and has some inventory ready for labelling and deployment upon regulatory approval.
It expects to have total capacity for more than hundred million doses of vaccine per annum through a combination of in house production and CMO capacity.
Cov-Compare, the vaccine’s Phase 3 trial, showed that VLA2001 ‘demonstrated superiority in terms of neutralizing antibody titer levels against the active comparator vaccine, AstraZeneca’s AZD1222, as well as non-inferiority in terms of seroconversion rates and a significantly better tolerability profile.’
On Thursday, Valneva announced it had started a rolling review with the EMA: based on non-clinical data and early clinical studies. Its application with the UK’s MHRA, started in August, remains under submission despite the cancellation of the UK contract.
Valneva says potential regulatory approvals are expected in the first quarter of next year.
Point of difference as Omicron spreads
The shot uses Valneva’s Vero-cell platform, which is used for the company’s licensed Japanese encephalitis vaccine, IXIARO. VLA2001 consists of inactivated whole virus particles of SARS-CoV-2 with high S-protein density, in combination with two adjuvants, alum and CpG 1018.
If authorized, the company’s inactivated vaccine would complement the currently available mRNA and viral vector vaccines in the EU, notes Thomas Lingelbach, chief executive officer at Valneva.
“The latest COVID-19 wave in Europe underlines the need for additional vaccines and we continue to believe that VLA2001 will contribute to addressing the pandemic. We are hopeful that our vaccine candidate might cross protect against variants to the SARS-CoV-2 virus and also have the flexibility, knowledge and resources to adapt if required.”
As an inactivated whole-virus candidate, Valneva says its vaccine could have advantages over other vaccines when it comes to the emerging Omicron variant.
“In contrast to other vaccines that target only the spike protein of the SARS-COV-2 virus, VLA2001 is developed using the entire SARS-CoV-2 virus envelope. Preserving the whole virus envelope is expected to elicit a broad immune response and together with the CpG1018 adjuvant may provide an improved immunological profile by boosting T-cell responses against additional SARS-CoV-2 proteins.”
The company will test for cross-neutralization of VLA2001 against Omicron. In addition, its says its technology platform can be adapted to new variants if required.
“The company has undertaken laboratory development and testing of variants, at its sites in France and Austria, including the production of viral seedstock for three earlier variants of concern, including Delta. Valneva produced a full scale pilot lot derived from the Alpha variant, validating the suitability of its well-established manufacturing process for variant-based vaccines.”
Meanwhile, another point of difference for the vaccine is that it could be used for immunization of at-risk individuals; as well as benefiting from standard cold chain requirements of 2 degrees to 8 degrees Celcius.
Rocky start for booster shot potential
Valneva has begun generating data to inform any regulatory discussions regarding a potential booster indication for VLA2001. The first data from a continuation of existing clinical trials (homologous) are expected in the first quarter of 2022. Additionally, Valneva is in the process of setting up a dedicated heterologous booster trial.
All of these trials will evaluate a booster shot provided at least six months after primary vaccination, as per the currently recommended interval for licensed COVID-19 vaccines.
However, its quest for booster shots has got off to a rocky start, with the publication of a study from the UK's COV-Boost trial - which analysed booster potential from different companies including Valneva - in The Lancet.
The study, funded by the UK Vaccine Taskforce and National Institute for Health Research, found that all of the seven vaccines studied were safe to use as a third dose (Oxford/AstraZeneca, Pfizer/BioNTech, Moderna, Novavax, Janssen, CureVac and Valneva).
However, while the Valneva shot boosted levels of spike protein antibodies significantly after an initial AstraZeneca regimen, it did not after an initial Pfizer/BioNTech regimen (the six other vaccines, in contrast, did).
Responding to the study, Juan Carlos Jaramillo, MD, Chief Medical Officer of Valneva defends the vaccine's potential as a booster. Participants in the COV-Boost trial were given a booster dose soon after the primary vaccination series: when they did not need a booster from either an immunological standpoint or under the currently recommended interval for licensed COVID-19 vaccines. The company believes the short interval between the second shot and booster shot could have adversely impacted the results for VLA2001 (a longer interval is generally required for inactivated vaccines).
“The setting in the study leads us to believe that COV-Boost does not allow any conclusions to be reached regarding the use of VLA2001 as a booster in a real-life setting," said Jaramillo. "The protective antibody threshold has not yet been established therefore relative increases in antibody levels should not be seen as indicative of efficacy.”
As Valneva is seeking authorization for a primary vaccination series, based on data from the Phase 3 Cov-Compare trial, the COV-Boost trial data will not be part of its submissions to the MHRA and EMA (nor were they originally intended to be).