With pivotal data on its Covid-19 antibody in hand, AstraZeneca prepares for a mad dash to the FDA
A month after revealing that its monoclonal antibody combination was 77% effective at preventing symptomatic Covid-19 compared to placebo, AstraZeneca says it’s headed to the FDA.
“We’ve certainly shared the data with regulators, and we anticipate submitting the emergency use authorization very shortly,” Mark Esser, VP and head of microbial sciences and biopharmaceuticals R&D, said during a press conference on Wednesday afternoon.
Just eight of 3,460 volunteers given AZD7442 in the Phase III PROVENT trial came down with symptomatic Covid-19 over a six-month period, Esser said, compared to 17 of 1,737 people in the placebo group.
The study enrolled participants across the US, UK, Spain, France and Belgium, many of whom had comorbidities or other conditions that would cause a reduced immune response to vaccination. That included people on immunosuppressive drugs, or with diseases like diabetes, smoking-related lung disease, kidney disease, and chronic liver disease, among others.
Overall, the therapy posted a 77% efficacy rate — a significantly higher rate than the 63% efficacy reported to the WHO for the company’s own Covid-19 vaccine. At an interim readout in March, AstraZeneca had reported that its vaccine was 70% effective at preventing symptomatic Covid-19, which was slightly higher than the 62% figure posted in the UK.
There were no severe cases or deaths in the AZD7442 treatment arm, and three severe cases and two deaths in the placebo arm, the pharma said. Though it’s unclear how the FDA may view the trial’s relatively small sample size.
Despite the positive efficacy results, Esser stressed that AZD7442 is intended for use on top of vaccination, not in lieu of it.
“First and foremost, we want people to get vaccinated. We know the vaccines work in most people,” he said. “Now, if there is someone who’s had an allergic reaction to one of the vaccines, or for some reason cannot get vaccinated, I think 7442 could be a solution for that.”
AZD7442 was discovered by the Vanderbilt University Medical Center, and licensed to AstraZeneca last June. It’s a combination of the antibodies tixagevimab and cilgavimab, derived from B cells donated by a husband and wife team who had recovered from Covid-19. The benefit of a monoclonal antibody is that it provides “almost immediate” protection, whereas current vaccines approved in the US take a couple weeks to kick in.
The downside is that the duration of protection is much shorter. AstraZeneca says it has technology that can extend the antibody’s half life from an average of around 20 days to 90 days.
“What this means is that a single intramuscular shot could easily afford six months, and we’re hopeful up to 12 months of protection,” Esser said on the call.
In addition to PROVENT, AZD7442 is also in the ongoing TACKLE COVID-19 program, which looks at the antibodies’ ability to treat and prevent Covid across more than 9,000 participants in the outpatient setting. And while volunteers got the candidate injected into the muscle in PROVENT, it’s also being assessed as an IV drug.
Back in June, AZD7442 missed the mark in a study assessing its ability to prevent symptoms in adults who had a confirmed exposure to Covid-19. AstraZeneca says the antibody combo performed better in a pre-planned analysis of PCR-negative volunteers.
Esser says he’s “quite confident” AZD7442 will work against the Delta variant, as well as other emerging variants, adding that there were few Delta cases reported in the treatment arm, and many in the placebo arm. He said the company is sequencing the viruses, and will have more data to share soon.
Hugh Montgomery, a professor of medicine and director of the Centre for Human Health and Performance at University College in London, pointed to the benefit of having two long-acting antibodies.
“If one was looking at the risk of viral escape down the line, the chances of getting two mutations to prevent these antibodies binding would be very, very unlikely,” Montgomery said.
The news comes a month after federal officials reauthorized Eli Lilly’s antibody combo, which had been taken off the market due to a “sustained increase” of coronavirus variants in the US. That combo — bamlanivimab and etesevimab — is now authorized in states where the frequency of resistant variants like the Delta-plus or Gamma is 5% or lower.