A new monoclonal antibody treatment has been found to protect chronically ill adults from developing COVID-19. The Phase 3 trial results suggest the novel antibody cocktail, delivered by intramuscular injection, could offer up to 12 months protection.
Antibodies are like our immune system’s front-line soldiers. They constantly circulate around the body, on the hunt for whatever specific pathogen they have been trained to target.
In early 2020 researchers at Vanderbilt University Medical Center homed in on a handful of particularly potent antibodies, isolated from some of the earliest detected COVID-19 patients. The antibodies were subsequently licensed by pharma company AstraZeneca and turned into monoclonal antibody treatments designed to prevent symptomatic COVID-19 infections.
The new treatment has been dubbed AZD7442 and the latest clinical trial results announced by AstraZeneca indicate it could play an important role in helping protect the most vulnerable from severe COVID-19.
The company’s recent announcement details results from a trial called Provent, which commenced in late 2020. The trial enrolled over 5,000 subjects, focusing on those most at risk of severe COVID-19 either due to chronic pre-existing illness or at risk of a weak response to vaccination due to being immunocompromised.
The newly announced results come from a primary analysis of the recently completed trial and are yet to be peer-reviewed or published in a journal. Over the course of a six-month follow-up period the trial saw no cases of severe COVID-19 or death in those patients receiving AZD7442. This compares to the placebo group that saw three severe COVID-19 cases, two of which led to death.
Overall, AstraZeneca indicates there were 25 symptomatic COVID-19 cases detected in the total trial cohort. AZD7442 was found to reduce a chronically ill person’s risk of symptomatic COVID-19 by 77 percent.
Provent is not the only clinical trial testing AZD7442, but it is the first to deliver promisingly positive data. Another trial, dubbed Storm Chaser, recently failed to meet its primary endpoint.
Storm Chaser was testing the same antibody cocktail as a post-exposure tool in those who had potentially been recently exposed to SARS-CoV-2 but had yet to test positive to the virus. After enrolling over 1,000 subjects in the Storm Chaser trial, AstraZeneca announced in June it had found no statistically significant difference in COVID-19 cases between placebo and AZD7442 groups.
Penny Ward, a researcher from King’s College London who did not work on these AstraZeneca trials, hypothesizes the different results between the two trials could be due to the fact AZD7442 is administered by intramuscular (IM) injection, which may be slower to take effect than if the treatment were delivered by intravenous infusion.
“What the Storm Chaser trial tells us is that IM injection does not provide an immediate level of antibody sufficient to cut off viral replication and prevent disease among individuals exposed to the virus who are already infected,” says Ward. “It would be interesting to see if earlier administration using an IV infusion would be more successful than IM injection in this setting.”
The simplicity of delivering this treatment by intramuscular injection is one of the factors that sets it apart from other recent monoclonal antibody treatments under investigation for COVID-19. Another novel feature of this monoclonal antibody treatment is its potential long-term efficacy.
AstraZeneca worked to optimize the half-life of these monoclonal antibodies and initial studies indicate a single treatment may produce effective protection for up to 12 months. This preliminary data analysis for the Provent trial covers six months of follow-up, with another nine months of observation to follow.
James Crowe Jr., from the Vanderbilt Vaccine Center, says this new treatment may be a game-changer for vulnerable subjects who don’t respond well to vaccines. Crowe Jr. was part of the Vanderbilt team working on the isolation of these potent antibodies in early 2020.
“It’s deeply gratifying to see the antibodies we isolated under challenging circumstances, in the middle of the international lockdown last spring, protecting the most vulnerable amongst us,” says Crowe Jr. “This single-shot prevention is likely to be a game changer for at-risk patients.”
Although the Provent trial took place prior to the emergence of the Delta variant, preliminary preclinical research indicates these monoclonal antibodies should still be effective at neutralizing current SARS-CoV-2 variants. AstraZeneca says it is preparing submissions to regulatory bodies for emergency use authorization of AZD7442.
Ward points out that until the full trial data is peer-reviewed and published the optimal method of administration for this novel monoclonal antibody in clinical practice is unclear. However, she does stress these findings are good news for those vulnerable patients worried their vaccination has not been completely effective.
“This could be very important as an option for patients at high risk from COVID infection who have responded poorly to vaccination or who must take immune-suppressing treatment for other disease (cancer, post-transplant, autoimmune disease etc),” says Ward. “Indeed it could potentially be game changing for these individuals, who are currently being advised to continue to shield despite being fully vaccinated.”
Source: AstraZeneca, Vanderbilt University Medical Center