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®.

2022 Status: Three Doses Neutralize Omicron—Valneva said January 19 that an initial laboratory study showed that serum antibodies induced by three doses of VLA2001 neutralized the Omicron variant. Sera from 30 participants in the Phase I/II VLA2001-201 trial (NCT04671017) were used in a pseudovirus assay to analyze neutralization of the ancestral SARS-CoV-2 virus as well as the Delta and Omicron variants. All 30 samples presented neutralizing antibodies against the ancestral virus and Delta variant, while 26 samples (87%) presented neutralizing antibodies against Omicron. The mean fold reduction of neutralization relative to the ancestral virus was 2.7-fold for Delta and 16.7-fold for Omicron.

Valneva said it was continuing to provide data to the European Medicines Agency (EMA), the UK Medicines and Healthcare products Regulatory Agency, and Bahrain’s National Health Regulatory Authority (NHRA) as part of rolling submissions for initial approval of VLA2001. The company said it continued to expect to complete these submissions in time to receive potential regulatory approvals in the first quarter.

2021 Status: Mixed Results in U.K. Booster Study—VLA2001 boosted antibodies in people initially vaccinated with COVID-19 Vaccine AstraZeneca, but did not provide a boost for people who initially were dosed with Pfizer/BioNTech’s COMIRNATY (BNT162b2), according to a U.K. study assessing antibody and neutralizing responses of seven vaccine candidates studied in participants who received an initial two doses of either COMIRNATY or COVID-19 Vaccine AstraZeneca, according to data from the U.K. COV-BOOST trial (ISRCTN, number 73765130) published December 2 in The Lancet.

Moderna’s COVID-19 Vaccine (mRNA-1273) and Pfizer/BioNTech’s COMIRNATY (BNT162b2) developed the highest boosts to antibody and neutralizing responses. Vaccines from AstraZeneca, Novavax (NVX-CoV2373), Johnson & Johnson (Single-Shot COVID-19 Vaccine), and CureVac (CVnCoV) also increased antibody levels for either initial vaccine when given as boosters, but to a smaller degree, the study found.

“Valneva believes it is likely that the short interval between the second shot and booster shot could have adversely impacted the results for VLA2001, given that a longer interval is generally required for inactivated vaccines,” Valneva said December 3 in a statement.

Between June 1 and June 30, 2021, 3498 people were screened. 2878 participants met eligibility criteria and received COVID-19 vaccine or control.

IDT Biologika Partners on Manufacturing–IDT Biologika has agreed to produce VLA2001’s drug substance at its Biosafety Level 3 facilities in Dessau-Roßlau, Germany, in addition to Valneva’s manufacturing site in Livingston, Scotland, IDT and Valneva said November 29. The value of the companies’ agreement was not disclosed.

EC Purchases Up to 60M Doses—Valneva said November 23 that it signed an advance purchase agreement (APA) with the European Commission (EC) to supply up to 60 million doses of its inactivated COVID-19 vaccine candidate, VLA2001, over two years. The APA—whose value was not disclosed—came after the EC announced earlier in November that it had approved the agreement.

Valneva said it expected to deliver 24.3 million doses during the second and third quarters of 2022, subject to approval of VLA2001 by the European Medicines Agency (EMA). The EC has the option to increase the initial firm purchase order up to a total of 60 million doses, the rest of which would be delivered in 2023.

Positive Phase III Data—Valneva on October 18 reported positive topline results from the Phase III Cov-Compare pivotal trial (VLA2001-301; NCT04864561) of VLA2001. The trial met its co-primary endpoints, the company said, by demonstrating superiority against AstraZeneca’s AZD1222 in terms of geometric mean titer for neutralization antibodies (803.5 vs. 576.6), as well as non-inferiority in terms of seroconversion rates (SCR above 95% in both treatment groups) at two weeks after the second vaccination (Day 43) in adults aged 30 years and older. T-cell responses analyzed in a subset of participants showed that VLA2001 induced broad antigen-specific IFN-gamma producing T-cells reactive against the S- (74.3%), N- (45.9%) and M- (20.3%) protein, Valneva added.

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:

● ANTIVIRAL
● VAX
● ANTIBODY
● RNA