Valneva, a specialty vaccine company focused on the development and commercialisation of prophylactic vaccines for infectious diseases with significant unmet medical need, has announced positive data for Part A of the Phase I/II clinical trial of its inactivated, adjuvanted Covid-19 vaccine candidate, VLA2001. Based on this data, the company plans to commence a Phase III clinical trial by the end of April 2021, subject to regulatory approval.
In study VLA2001-201, three dose levels of VLA2001 (low, medium, high), based on a schedule of two doses with vaccinations three weeks apart, were evaluated in 153 healthy adults aged 18 to 55 years.
VLA2001 was generally safe and well tolerated across all dose groups tested, with no safety concerns identified by an independent Data Safety Monitoring Board. There were no statistically significant differences between dose groups and no differences between first and second vaccinations in terms of reactogenicity. The majority of Adverse Events (AEs) were mild or moderate and only two subjects reported severe solicited AEs (headache and fatigue). All solicited AEs were transient. Only 17.6% of unsolicited AEs up to day 36 were considered related to the vaccine and no severe unsolicited AEs were reported. No serious related AEs were reported.
VLA2001 was highly immunogenic with more than 90% of all study participants developing significant levels of antibodies to the SARS-CoV-2 virus spike protein across all dose groups tested. Seroconversion Rates (SCR) for S-protein binding IgG antibodies were 89.8% in the medium dose and 100% in the high dose group. Two weeks after completion of the two dose schedule, Geometric Mean Fold Rise (GMFR) from baseline were 26 in the medium dose and 86 in the high dose group.
Of note, the IgG antibody response was highly correlated with neutralisation titres in a micro-neutralisation assay (MNA50) (r=0.79, p<0.001).
VLA2001 induced a dose dependent response with statistically significant higher Geometric Mean Titres (GMTs) for both IgG and neutralising antibodies in the high dose group compared to the low and medium dose groups. In the high dose group, the GMT of neutralising antibody titres measured two weeks after completion of the two-dose schedule was at or above levels for a panel of convalescent sera (GMT 530.4 (95% CI: 421.49, 667.52)).
With a GMT ratio of vaccine vs. convalescent sera ≥ 1 vaccine efficacy has been reported above 80% for other vaccines.
VLA2001 induced broad T-cell responses across participants with antigen-specific IFN-gamma producing T-cells against the S-protein, M and N protein detected in 75.6 %, 35.6% and 48.9% of study participants, respectively.
Thomas Lingelbach, Chief Executive Officer of Valneva, said: “We are extremely pleased with these results which take us a step closer to providing an inactivated vaccine to help the global fight against Covid-19. The world needs multiple vaccines as well as booster options. Given the potential advantages often associated with inactivated whole virus vaccines, we believe that VLA2001 has an important role to play. This includes potential modifications to the vaccine to address variants, using our existing manufacturing process. I want to thank everyone involved in the ongoing work. We could not have achieved this milestone without them.”
Clive Dix, Chair of the Vaccines Taskforce said: “These are great results from Valneva, particularly around the antibody and cellular responses generated and low numbers of adverse events, as these indicate good levels of immune responses among the participants to date. The findings of 100% levels of immunogenicity against the viral spike protein in the high-dose group is also encouraging. Inactivated virus vaccines are proven technologies that are often able to induce wide-ranging immune responses, and these promising data indicate that VLA2001 may continue this trend. We are hopeful of seeing good results from the upcoming Phase III trials, and look forward to continuing working closely with Valneva on their vaccine.”
Based on the data assessed, the company has decided to advance the high dose into the Phase III clinical trial. Other trials, including booster trials, involving antigen sparing doses will also be evaluated.
Valneva believes that the timeline for delivery of 60 million doses of vaccine to the UK Government will extend into the first quarter of 2022. Based on the Phase I/II data, the company is also investigating antigen sparing options for booster strategies. Overall capacity and delivery schedule will be dependent on the UK’s vaccine requirements and production related factors.
Valneva plans to initiate a pivotal, comparative immunogenicity Phase III clinical trial by the end of April 2021 with the aim of making a regulatory licensure submission to the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK in the autumn 2021. Discussions with other regulatory bodies are ongoing.
In parallel, Valneva has initiated the development of new variant based viral seed banks.