Astrazeneca’s swift advancement into pivotal trials of AZD2816, a booster vaccine optimised for the Covid-19 Beta variant, will have softened the blow of a US delay to the group’s original vaccine, Vaxzevria. Today Astra confirmed that Vaxzevria’s US regulatory path would comprise a full BLA filing rather than a much quicker emergency use authorisation.
Still, many had long suspected that pursuing a BLA was inevitable, and perhaps the bigger question now is when Astra might start making a profit on Vaxzevria. This is also relevant if next-generation vaccines gain importance – something echoed by Pfizer, which pressed its own case for boosters during its earnings call yesterday.
Astra’s commitment to provide Covid-19 vaccines at cost while the current pandemic persists marks one difference between the two companies. While yesterday Pfizer booked $7.8bn of second-quarter Comirnaty sales, fuelling an earnings uplift, today Astra reported $1.1bn of first-half Vaxzevria revenue, at zero profit.
Presumably the UK group’s commitment will extend to AZD2816, but a switch to booster shots might be one indication that the initial pandemic, at least in many western countries, is over. On a call today Astra’s chief executive, Pascal Soriot, offered no specific guidance, and said his goal was to deliver on doses ordered so far, all at cost.
But focus will fall increasingly on a phase 2/3 study of AZD2816. This has two parts, the first in subjects already vaccinated with two doses of Vaxzevria or an mRNA vaccine, giving subjects a booster dose of either Vaxzevria or AZD2816, and is expected to yield data in the current quarter, leading to UK filing by the year end.
The second part is designed for rest-of-world approval, and is in unvaccinated individuals, testing two doses of Vaxzevria or AZD2816. Data are expected by the end of the fourth quarter. Interestingly, this booster programme appears to be an answer to a waning efficacy problem that Astra does not yet accept it has.
Not so Pfizer, which yesterday showed waning neutralising antibody level data eight months after the second Comirnaty dose, highlighting how levels increased again after a third shot.
The obvious question, of course, is whether declining antibody levels correlate with decreasing vaccine efficacy. Pfizer said it was now getting reports of breakthrough infections in countries other than Israel, one of the first to launch its vaccination programme.
This stance was further strengthened by long-term data from Comirnaty’s phase 3 trial, published as a preprint yesterday, showing vaccine efficacy slipping to 84% at six months, though efficacy against severe disease was 97%.
For its part, however, Astra said antibody levels were just one part of the immune response; another was T cells. “Adeno vector vaccines tend to stimulate large production of T cells, and it’s quite possible that these will provide long-lasting protection,” said Mr Soriot, though he too accepted some loss of antibodies over time after Vaxzevria.
If boosters do become the norm, the next question is whether they might be a one off or be given periodically. Pfizer’s chief scientific officer, Mikael Dolsten, said he “would not be surprised” if a Covid-19 shot would be needed at regular intervals. This could be either annual or based on a diagnostic, he added.
Pfizer plans to ask for emergency use authorisation (EUA) of a booster by August, when it will also start clinical trials of a Delta-specific vaccine. A separate issue is that the US Centers for Disease Control and FDA have initially come out against Covid-19 boosters.
For Astra, before AZD2816 becomes reality Vaxzevria probably needs to make it across the US finish line. The initial vaccine has suffered repeated delays, and work is now under way to gather sufficient data for a pre-BLA meeting, and to start a rolling BLA filing by the year end.
“The reason it’s taking a long time is because the FDA is requesting an awful lot of information,” said Mene Pangalos, Astra’s head of biopharmaceuticals R&D. This apparently includes UK, Brazil, Africa and US studies, in addition to real-world data.
It is also possible that full BLA approval will boost Astra’s chances of raising Vaxzevria’s price. Mr Soriot stressed that Astra does not intend to make a “large profit”, but said that “at some point in the future we will move to an affordable price. We can’t be at no profit forever.”