AstraZeneca’s anti-SARS-CoV-2 antibody combination has failed a phase 3 clinical trial designed to assess its ability to prevent symptomatic COVID-19 in people recently exposed to the pandemic coronavirus.
While the Storm Chaser study missed its primary endpoint, a subgroup analysis of people who tested negative for COVID at baseline offered encouragement to AstraZeneca.
The trial miss was another chapter in the U.K. pharmaceutical giant's COVID-19 program, which includes a widely-used vaccine to prevent the respiratory disease. Reports of blood clots in some recipients of the jab stalled the roll out in some countries.
In Storm Chaser, investigators enrolled 1,121 adults who had a potential exposure to an individual with a confirmed SARS-CoV-2 infection in the past eight days. Two-thirds of the participants were randomized to get a single intramuscular dose of AZD7442, AstraZeneca’s long-acting antibody combination. The other one-third of participants received saline placebo.
Twenty-three of the 749 recipients of AZD7442 went on to develop a confirmed case of symptomatic COVID-19, compared to 17 of the 372 subjects who got placebo. The difference amounted to a 33% relative risk reduction but fell short of statistical significance, causing the trial to miss its primary endpoint.
The primary endpoint analysis included 48 participants who were confirmed positive at the start of the study. Half of the 34 positive subjects in the AZD7442 cohort developed symptomatic COVID-19. In the placebo group, six of the 14 positive participants developed symptoms.
Excluding the confirmed positive subjects tipped the balance in favor of AZD7442. The preplanned analysis of confirmed negative participants featured 715 people who received the antibody combination. Six of the baseline negative subjects who received AZD7442 went on to develop symptomatic COVID-19. In the placebo group, 11 of the 358 baseline negative participants developed symptoms.
The relative risk reduction in the preplanned subgroup was 73%. AstraZeneca also performed a post hoc analysis that divided the baseline confirmed negative subgroup depending on how long after dosing a subject developed symptoms. The analysis found AZD7442 cut the risk of symptomatic COVID-19 by 92% more than seven days following dosing. The relative risk reduction fell to 51% in the first seven days after dosing, although as a post hoc analysis limited conclusions can be drawn from the finding.
In a statement, Mene Pangalos, Ph.D., executive vice president for biopharmaceuticals R&D at AstraZeneca, said the company is “encouraged by the protection seen in the PCR-negative participants.” Pangalos pointed to upcoming readouts from two other clinical trials as events that will shape the role AZD7442 plays in the management of COVID-19.
One of the studies, Provent, is giving AZD7442 to people who haven’t been exposed to the virus to show whether the antibody combination can protect against COVID-19. Success in Provent could establish AZD7442 as a way to prevent COVID-19 in people who are unable to be vaccinated or have a limited response to vaccines. The other study, Tackle, is testing whether AZD7442 can prevent outpatient adults with COVID-19 from developing severe disease.
While the rollout of vaccines has slowed infections, treatments for patients who contract COVID-19 are still needed—especially those that can tackle virus variants. Eli Lilly recently had to roll back one treatment after it was found ineffective against the variants.