Candidate: VLA2001

Category: VAX

Type: Vaccine candidate against SARS-CoV-2 consisting of inactivated whole virus particles of SARS-CoV-2 with high S-protein density, in combination with two adjuvants, alum and Dynavax’s CpG 1018. VLA2001 is produced on Valneva’s established Vero-cell platform, leveraging the manufacturing technology for Valneva’s licensed Japanese encephalitis vaccine, IXIARO®.

2021 Status: UK ENDS SUPPLY AGREEMENT–Valneva acknowledged September 13 that it received a termination notice from the UK Government related to the Supply Agreement for VLA2001. The government has alleged that Valneva has breached the agreement—an assertion Valneva said it “strenuously” denied.

The UK had about 100 million doses on order, after increasing its request by 40 million in February.

Valneva said the pivotal Phase III Cov-Compare trial remained ongoing at Public Health England, with results from the study expected to be available early in the fourth quarter. These results will form part of Valneva’s rolling submission for conditional approval of VLA2001 with the UK’s Medicines and Healthcare products Regulatory Agency (MHRA). Subject to the data and MHRA approval, Valneva added, it believes that approval for VLA2001 could be granted in late 2021.

Phase III Trial Launched–Valneva said August 11 that it has launched an additional Phase III trial, VLA2001-304 (NCT04956224) for VLA2001. The trial aims to generate data in the elderly and is also designed to potentially enable variant-bridging through immune-comparability. Data from this study is expected to complement ongoing clinical trials and support additional regulatory submissions, Valneva said.

VLA2001-304, which will be conducted in New Zealand, will recruit approximately 150 participants aged 56 years and older (Cohort 1) with the aim of generating additional safety and immunogenicity data in this age group following vaccination with VLA2001 (two doses 28 days apart).

Valneva said June 3 that it had completed recruitment for the pivotal Phase III Cov-Compare trial (VLA2001-301; NCT04864561) of VLA2001, which uses Dynavax’s CpG 1018™ adjuvant. The trial compares VLA2001 against AstraZeneca’s COVID-19 vaccine, known as Vaxzevria in the E.U., in a comparative immunogenicity trial.

Valneva initiated Cov-Compare on April 21. More than 4,000 volunteers in the U.K. have been randomized in the trial, whose primary endpoint is the immune response, measured in Geometric Mean Titer (GMT), of SARS-CoV-2-specific neutralizing antibodies two weeks after completion of a two-dose immunization schedule administered in a four-week interval. Topline data are expected by September. If positive, they will be submitted to the UK’s Medicines and Healthcare products Regulatory Agency for regulatory approval.

Cov-Compare will also evaluate the safety and tolerability of VLA2001 at two weeks after the second vaccination in adults aged 18 years and older. The trial is supported by the National Institute for Health Research (NIHR), Valneva said.

On April 6, Valneva said it planned to commence the pivotal Phase III trial by the end of the month, after the companies reported positive initial results for Part A of the Phase I/II trial (NCT04671017) of VLA2001 with CpG 1018 adjuvant in 153 healthy adults aged 18-55 years.

Valneva said VLA2001 was generally safe and well tolerated across all dose groups tested and was highly immunogenic with a seroconversion rate for S-protein binding IgG antibodies of 100% in the high dose group. The IgG antibody response was highly correlated with neutralization titers in a micro-neutralization assay.  The geometric mean titer of neutralizing antibodies measured two weeks after completion of the two-dose schedule in this group was at or above levels for a panel of convalescent sera.

In announcing fourth quarter and full-year 2020 results on February 25, Dynavax said it expects to generate revenue of up to $230 million in 2021 through the supply of CpG 1018 adjuvant for up to 100 million doses of Valneva’s COVID-19 vaccine VLA2001. Also that day, Valneva said separately that should an ongoing Phase I/II trial generate positive results, and should it receive needed regulatory approval, it plans to proceed “expeditiously” into Phase III development of VLA2001.

Valneva said January 28 that it had begun production of VLA2001 in parallel to its ongoing clinical studies, in order to optimize the timeline for potential deliveries of the vaccine. The Phase I/II trial is now fully enrolled, with a total of 150 healthy adults aged 18 to 55 years having been recruited, and is expected to report initial results in April 2021, according to the company.

Earlier in January, Valneva said it was in advanced discussions with the European Commission to supply of up to 60 million doses of VLA2001.

2020 Status: Valneva said December 16 that it had initiated a Phase I/II trial (NCT04671017) assessing the safety and immunogenicity for three dose levels of VLA2001 in approximately 150 healthy adults. The study will be conducted in study sites across the U.K., and is supported by the National Institute for Health Research (NIHR). The trial’s primary endpoint read-out will be two weeks after completion of the two-dose primary immunization (day 0, 21).

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. Valneva said it plans to include more than 4,000 participants in additional trials, which it believes could support an initial regulatory approval as soon as the fourth quarter of 2021.

VLA2001 leverages the manufacturing platform of Valneva’s licensed Japanese encephalitis vaccine IXIARO®, and according to the company is the first publicly announced inactivated vaccine against COVID-19 to commence clinical development in Europe.

On September 14, Valneva said it signed a major COVID-19 vaccine partnership with the U.K. government for the supply of up to 190 million doses of VLA2001. Under the partnership agreement, if vaccine development is successful, Valneva agreed to provide the UK government with 60 million doses in the second half of 2021 at a cost of €470 million (about $570 million), with options for more than another 130 million doses between 2022 and 2025.

Also that day, Valneva and Dynavax signed a commercial partnership thorugh which Dynavax’s CpG 1018 adjuvant will be supplied for use in VLA2001. Dynavax will supply CpG 1018 to produce up to 100 million doses of vaccine in 2021. Valneva has the option to purchase up to an additional 90 million doses through 2025.

COVID-19: 300 Candidates and Counting

To navigate through the >300 potential therapeutic and vaccine options for COVID-19, GEN has grouped the candidates into four broad categories based on their developmental and (where applicable) clinical progress:

FRONT RUNNER – the most promising therapeutics/vaccines based on clinical progress, favorable data or both.

DEFINITELY MAYBE – earlier phases with promising partners, or more advanced candidates in development that have generated uneven data.

KEEPING AN EYE ON… – interesting technology, attracting notable partners, or both, but preliminary data.

TOO SOON TO TELL – longshots pending additional experimental and/or clinical data.

GEN has also tagged the most common treatment types: