Source : 'Scrip Intelligence'
Valneva SE is not among the best known companies in the vaccines field, but the niche player could be about to move into the big league, thanks to its COVID-19 vaccine candidate.
Established in 2013 and headquartered in Nantes, France, the company is set for a transformation if its inactivated vaccine VLA2001 can prove its value against COVID-19 and join what its CEO Thomas Lingelbach calls the ‘third wave’ of vaccines.
These would follow the first wave, led by Pfizer Inc./BioNTech SE,Moderna, Inc. and AstraZeneca PLC, which already have emergency authorization in the US and/or EU, and second-wave vaccines from J&J and Novavax, which have their Phase III data and are awaiting regulatory review.
Following high profile frontrunners with excellent efficacy rates is a tricky proposition, but different types of COVID-19 vaccines, and many more millions of doses, are still needed to beat the pandemic.
Valneva’s entry into the race is thanks largely to support from the UK’s Vaccines Taskforce, putting VLA2001 in a portfolio of seven it has supported with advance purchase agreements.
The Taskforce agreed to buy 60 million doses in September, and on 1 February increased this to 100 million doses. Equally importantly, the UK government has jointly financed the creation of Valneva’s new vaccines manufacturing site in Livingstone, Scotland, to enable the delivery of the first doses by late 2021.
The UK government retains the option for a further 90 million doses for supply between 2023 and 2025. Valneva has said that if all options are exercised on the full 190 million doses is exercised, the substantial deal will be worth up to €1.4bn ($1.7bn).
The company is also now in advanced discussions with the European Commission regarding supply of up to 60 million doses. These deals would certainly transform the company’s near-term fortunes, which so far have been based on two marketed travel vaccine products, Ixiaro for Japanese encephalitis and Dukoral for cholera.
Sales of these products declined by more than 25% in the first nine months of 2020 because of the pandemic’s impact on travel, leaving the company with revenues of just under €59,000, and a similarly sized operating loss.
Much will depend on the success of its COVID candidate VLA2001, which is due to produce all-important Phase I/II data by early April. The study will focus on safety, immunogenicity, and optimal dose for further development, and will set it up for a larger pivotal trial.
VLA2001 is based on inactivating a live SARS-CoV-2 virus, a technology that has been around since the 1950s, and has largely been left behind by the big players in the US and Europe in favor of protein subunit vaccines, or the novel viral vector and mRNA-based products.
Inactivated vaccines generally have a good safety profile and are easy to administer, but downsides can include limited neutralizing antibody levels, and a short duration of protection.
Notably, two out of three of China’s emergency authorized COVID-19 vaccines are inactivated vaccines. Of these, Sinovac’s Coronavac has the most evidence behind it, with its pivotal trial producing a relatively low 50.4% efficacy rate, although this result came with confidence of 35-62%, and no-one in the vaccinated group had severe Covid-19 or required hospitalization for the illness.
Valneva uses a similar approach to Sinovac, in using the well-established alum adjuvant to boost its immunogenicity. But Valneva is also adding a second adjuvant, Dynavax’s toll-like receptor agonist CpG 1018, already used in that company’s hepatitis B vaccine Heplisav-B.
Asked just how much the novel adjuvant could boost the immunogenicity of the vaccine, Ligenbach commented that this was the “$3bn question” for his company. CpG 1018 is intended to enhance the TH1 cellular response, which is necessary for antibody and cellular immunity.
“We will not necessarily see an improvement on the neutralizing antibody titers [with CpG 1018], but probably better quality of the immune response. This could have advantages for example, in the elderly, and could have also advantages in other vulnerable populations.”
There are extra hurdles to overcome for third wave COVID-19 vaccines looking to enter clinical trials in mid-2021. Most significantly, the ethical issues of conducting placebo-controlled trials when several authorized vaccines are available, and the fact that most of the elderly population , the most crucial cohort, will have generally already been vaccinated in developed markets by this point.
Lingelbach said Valneva was now in discussions with regulators about what alternative clinical trial designs could be used to generate data sufficient for authorization. “We, like others, are favoring a non-inferiority, head-to-head immunogenicity trials with immunological endpoints and comparators against one of the licensed vaccines.”
This tactic is being employed by Sanofi and GSK, whose much delayed protein subunit vaccine will go head-to-head with one of the mRNA-based vaccines.
But what is needed is the determination of an immune correlate of protection (CoP) for COVID-19 that can gain the confidence of regulators and serve as a surrogate endpoint for vaccine efficacy. This would allow newer entrants to gain authorization without large-scale Phase III trials.
Many experts believe a CoP is likely to come, but timing is key for Valneva; scientific clarity on a correlate might come too late for it to stay on track to deliver a vaccine by the end of 2021..
It is therefore keeping its options open and preparing for a possible classical pivotal trial, but Lingelbach said this could only take place in regions beyond Europe and the US where COVID-19 vaccine penetration remains low.
All COVID-19 vaccine developers are having to field questions about their readiness to respond to the threat of new variants. Lingelbach said this was a positive advantage of an inactivated vaccine, the standard platform for influenza vaccines, which are updated each flu season to adapt to the latest strains.
He said this could be achieved against new COVID-19 strains as well via “relatively small” immunological bridging studies. Once these are completed, Valneva’s production of the new vaccine would typically take 100 days from the start of manufacturing to having the first doses available.
Lingelbach said Valneva was pleased to be contributing in the battle against SARS-CoV-2, but was cautious about saying this would lead to a turning point for the company.
“Whether COVID will become a long-term business for Valneva and hence a transformational piece of its strategy, has to be seen. None of us can predict how long we will need to have vaccination strategies around COVID. But certainly, it is important that we also built our manufacturing capacity, and this certainly helps the company to position itself going forward.”
Also in the company’s pipeline is a vaccine program for mosquito-borne Chikungunya infection in Phase III. This is the most advanced of any company, although Moderna also has a candidate in Phase II.
The company’s lead R&D program in terms of size of unmet medical needs and potential market opportunity is Lyme Disease. Valneva is the only company in the world with a Lyme disease vaccine in clinical development, and this is expected to hit its Phase II endpoints in October.
The company signed a co-development and co-commercialization deal with Pfizer in May last year. Analysts forecasting this could be worth peak annual sales of up to $900m ($1bn). ()
This and the potential of VLA2001 has prompted Valneva’s plans for a new fundraising via a secondary listing on the US Nasdaq exchange, to take place in the first half of 2021.
This will act as a further catalyst for growth, though the company has not yet looked at expanding into the US market. Lingelbach said the company planned to establish contact with the US Food and Drug Administration once its COVID-19 vaccine has entered Phase III trials.
By Andrew McConaghie