Astra flunks its first Covid-19 antibody test
But AZD7442 still has two more bites at the cherry.
Astrazeneca had hoped that a longer half-life and more convenient intramuscular dosing would give its Covid-19 antibody AZD7442 an edge over the competition. But the project’s first big test, in post-exposure prevention, has drawn a blank.
It might be that the trial was just too small to tease out a benefit, and there was a key finding in people who had no detectable virus at baseline, which in hindsight might have been a more logical population; Astra is not saying yet if it is pressing on in this setting. But attention now turns to the Provent study in pre-exposure prevention. One worry here is whether there will be enough cases of Covid-19 to drive a result.
The study that failed today, Storm Chaser, enrolled 1,121 unvaccinated adults who had been exposed, within the prior eight days, to someone infected with Covid-19. Participants had to have a negative Covid-19 antibody test on the day of dosing to exclude prior infection. On the same day they also underwent a PCR test to see whether or not they harboured the virus at baseline.
In the overall population, AZD7442 reduced the risk of developing symptomatic Covid-19 by 33% over placebo, but this was not statistically significant. With such a small number of participants, perhaps the study was underpowered.
Regrettably for Astra this primary endpoint failure meant that none of the other analyses of the trial, one of which was planned, are significant either, despite their showing some interesting trends.
The pre-planned analysis found that, in patients with a negative PCR test at baseline, AZD7442 reduced the risk of developing symptomatic Covid-19 by 73% versus placebo. This is an intriguing finding, so perhaps in hindsight by including in the primary analysis patients positive by PCR at baseline Astra had cast the net too widely.
Asked whether the subgroup result might be enough to file AZD7442 for emergency use authorisation, an Astra spokesperson told Evaluate Vantage: “We are awaiting results from Provent before determining our EUA plans.”
Still, the future for AZD7442 in post-exposure prevention does not look rosy, particularly after a win for Regeneron’s antibody doublet, casirivimab plus imdevimab, in Study 2069 – a trial in a similar setting. That used a subcutaneous formulation, also wiping out any potential convenience advantage for AZD7442. The original formulation of the Regeneron project was intravenous.
So hopes for the Astra antibody now turn to Provent, results from which are expected soon. That trial, in around 5,000 vulnerable or at-risk people, is testing AZD7442 for pre-exposure prophylaxis of Covid-19. In effect, AZD7442 is being used as a “passive vaccination” for people who are not suitable candidates for a conventional vaccine, such as those who are immunocompromised.
One question is whether Provent, which is being run in the US and Europe, can accrue enough cases of Covid to show a significant difference between AZD7442 and placebo. Even if AZD7442 does prevail this will be a small niche.
AZD7442 is also in another study, Tackle, for the treatment of Covid-19 outpatients, with data due in the second half of the year. However, this market has been sewn up by Regeneron and Lilly – and even with only two players in the mix, sales have been disappointing.
|Storm Chaser (NCT04625972)||Post-exposure, in subjects exposed to infection||Failed primary endpoint Jun 2021|
|Provent (NCT04625725)||Prophylactic, in subjects unsuitable for vaccination||Data due "soon"|
|Tackle (NCT04723394)||Outpatient, dosing no more than 7 days from symptom onset, oxygenation saturation ≥92%||Data due H2 2021|
|Source: Evaluate Pharma & clinicaltrials.gov.|
Details on Study 2069 on Regeneron's casirivimab plus imdevimab have been updated.