Valneva scores a pyrrhic trial win
The group’s Covid-19 vaccine is on course for UK approval – but the UK doesn’t want it.
Judging by the 36% share price rise so far today, Valneva’s investors firmly believe that VLA2001 is on course to become the first Covid-19 vaccine to be approved in the UK without a placebo-controlled clinical trial.
Today’s top-line phase 3 data show that the jab bested Astrazeneca’s Vaxzevria in terms of both antibody levels and seroconversion rates, and Valneva has previously said that immunogenicity data alone ought to be enough to secure UK approval. From a financial angle, though, the point is largely moot, since the UK government cancelled its supply contract with Valneva a month ago.
The phase 3 Cov-Compare trial positioned VLA2001 head-to-head with Vaxzevria, placebo-controlled trials now being considered unethical and hard to enrol anyway. The trial focused on immunological measure, with VLA2001 producing significantly higher levels of neutralising antibodies than Astra’s vaccine, and similar rates of seroconversion.
These endpoints were measured two weeks after the second vaccination in 2,972 adults aged 30 years and older, despite the trial enrolling a total of 4,012 participants aged 18 and up plus 660 adolescents. Those in the 18-29 bracket were not included in today’s efficacy analysis, and the safety analysis was split by age group only for the VLA2001 group, making a direct comparison with the Vaxzevria group tricky.
|Top-line data from Cov-Compare|
|Geometric mean titre for neutralisation antibodies||803.5||576.6||Geometric mean titre ratio 1.39 vs Vaxzevria, superior, p<0.0001|
|Any adverse event|
|Subjects aged 18-30||92.6%|
|Subjects aged 30yrs+||88.7%|
|Subjects aged 18+||98.1%|
|Injection site reactions||73.2%||91.1%||p<0.0001|
|All VLA2001 data concern patients 30yrs and older, except where specified. T-cell data from an unspecified subgroup. Source: company release.|
The interval between doses also makes comparison harder. In both arms of the trial the shots were given four weeks apart; Vaxzevria’s UK label specifies an interval of four to 12 weeks, but almost all those who have received the shot in clinical practice have had their second Vaxzevria jab two to three months after the first.
The trial did look at infection rates, though only as an exploratory endpoint. Valneva said that the number of Covid-19 cases was similar between treatment groups, and there was a complete absence of severe Covid-19.
If the data have answered at least some clinical questions, regulatory and commercial questions remain. A rolling MHRA submission was begun in August, and Valneva's chief executive Thomas Lingelbach said on a conference call today that this could be completed next month, with approval possible by the end of the year.
Assuming the MHRA grants authorisation, what then? Cancellation of the UK’s 100-million-dose supply contract last month deprived Valneva of a ready market, though it is possible that UK authorisation could lead to WHO approval and widespread use in the developing world under the Covax programme (Valneva falls as UK contract axe falls, September 13, 2021).
There is another possible niche. Much research is ongoing into the potential of heterologous booster regimens, since some data have suggested that a mix-and-match approach can produce better responses than a third shot of the same vaccine. This was a topic at the panel meeting discussing Johnson & Johnson’s vaccine last week (US backs another Covid-19 booster, October 15, 2021).
A UK study of heterologous booster usage, Cov-Boost, is ongoing, and VLA2001 is one of the seven Covid-19 vaccines being studied. As an adjuvanted inactivated whole virus, the only such Covid-19 vaccine candidate in trials in Europe, VLA2001 could be a good candidate to follow both the mRNA jabs and Astra’s vaccine, which is based on a chimp adenovirus.
Valneva is also pursuing its own 200 subject-strong booster trial of VLA2001, but it is not clear when either this or Cov-Boost might report.
The French group is also planning a European filing for the vaccine, though it is unclear whether immunogenicity data alone will be enough for the EMA. The company is also having discussions with regulators in Asia.
Stifel analysts are bullish, having pencilled in EU approval for 2022. They write that worldwide, Valneva could sell 95 million doses in 2022 and 120 million each in 2023 and 2024 before demand ceases. This could bring in annual revenues of over $1bn from 2022, they write. They have not included any UK government sales in this forecast.