Trial participants were unvaccinated adults 18 years and over with confirmed exposure to a person with a case of the SARS-CoV-2 virus within the past eight days. In the overall trial population, AZD7442 reduced the risk of developing symptomatic COVID-19 by 33% (95% confidence interval (CI): -26, 65) compared to placebo, which was not statistically significant (Table 1).

The trial included 1,121 participants in a 2:1 randomisation AZD7442 to placebo, with 23 cases of symptomatic COVID-19 accrued in the AZD7442 arm (23/749) and 17 cases accrued in the placebo arm (17/372). All participants had a negative SARS-CoV-2 antibody test on the day of dosing to exclude prior infection, and a nasopharyngeal swab was also collected and subsequently analysed for SARS-CoV-2 by RT-PCR to detect virus.

Given the importance of finding therapies for COVID-19 and to help interpret trial results during the pandemic, additional analyses were performed and are being communicated (Table 1).

In a pre-planned analysis of SARS-CoV-2 PCR positive (detectable virus) and PCR negative (no detectable virus) participants, AZD7442 reduced the risk of developing symptomatic COVID-19 by 73% (95% CI: 27, 90) compared with placebo, in participants who were PCR negative at time of dosing. In a post-hoc analysis, in participants who were PCR negative at baseline, AZD7442 reduced the risk of developing symptomatic COVID-19 by 92% (95% CI: 32, 99) versus placebo more than seven days following dosing, and by 51% (95% CI: -71, 86) up to seven days following dosing.

Myron J. Levin, MD, Professor of Pediatrics and Medicine, University of Colorado School of Medicine, US, and principal investigator on the trial, said: "The results of STORM CHASER suggest that AZD7442 may be useful in preventing symptomatic COVID-19 in individuals not already infected. The PROVENT trial will give us more clarity in this patient population. While COVID-19 vaccination efforts have been successful, there is still a significant need for prevention and treatment options for certain populations, including those unable to be vaccinated or those who may have an inadequate response to vaccination."

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: "While this trial did not meet the primary endpoint against symptomatic illness, we are encouraged by the protection seen in the PCR negative participants following treatment with AZD7442. We await results from PROVENT, our pre-exposure prevention trial and TACKLE, our treatment trial in preventing more severe disease, to understand the potential role of AZD7442 in protecting against COVID-19."

[][][]
Table 1: STORM
CHASER analyses
Baseline Onset of Number of Relative risk
subgroup case post cases / reduction
dose number of (95% confidence
participants interval)
AZD7442 (300mg Placebo
IM)
All All cases 23 / 749 17 / 372 33% reduction[a]
participants (-26 to 65)
(Primary
analysis)
PCR-negative[b] All cases 6 / 715 11 / 358 73% reduction
(Pre-planned (27 to 90)
subgroup
analysis)
PCR-negative[b] ≤7 days 5 / 715 5 / 358 51% reduction
(Post hoc (-71 to 86)
subgroup
analysis)
>7 days 1 / 710 6 / 353 92% reduction
(32 to 99)
a: Not
statistically
significant.b:
Includes 974
participants
(15 cases)
confirmed PCR
negative at
baseline and 99
participants (2
cases) with PCR
status missing
at baseline.48
participants
were confirmed
PCR positive at
baseline with
23 cases
(AZD7442:
17/34; placebo:
6/14).

AZD7442 was well tolerated in the trial. Preliminary analyses show similar adverse events in the placebo and treatment arms.

Full results from STORM CHASER will be submitted for publication in a peer-reviewed medical journal and presented at a forthcoming medical meeting.

Financial considerations

On 16 March 2021, AstraZeneca announced (https://www.astrazeneca.com/media-centre/press-releases/2021/us-supply-agreement-for-additional-azd7442-doses.html) an extended agreement with the US Government to supply up to 500,000 additional doses of AZD7442 for $205m, contingent on AZD7442 receiving Food and Drug Administration Emergency Use Authorisation in post-exposure prophylaxis. Discussions regarding next steps with the US Government are ongoing.

STORM CHASER

STORM CHASER is a Phase III, randomised, double-blind, placebo-controlled, multi-centre trial assessing the safety and efficacy of a single 300mg dose of AZD7442 compared to placebo for the post-exposure prevention of COVID-19. The trial was conducted in 59 sites in the UK and US. 1,121 participants were randomised in a 2:1 ratio to receive a single intramuscular (IM) dose of either 300mg of AZD7442 (n=749) or saline placebo (n=372), administered in two separate, sequential IM injections. The primary efficacy endpoint is the first case of SARS-CoV-2 RT-PCR-positive symptomatic illness occurring post dose to Day 183. The primary analysis was to be conducted 30 days after 25 events meeting the primary efficacy endpoint definition had occurred. This primary analysis includes data and additional events accumulated up to 7 April 2021, 30 days after the symptom assessment date of the 25th event; participants will continue to be followed for 15 months.

The post hoc analysis looked at cases of symptomatic COVID-19 in the PCR-negative group occurring seven days or less after dosing and more than seven days after dosing. This was based on the known incubation period of SARS-CoV-2. Cases occurring more than seven days after dosing are likely to be due to infection that occurred after dosing rather than before.[1]

Participants were adults 18 years and over with potential exposure, within eight days, to a specific identified individual with laboratory-confirmed SARS-CoV-2 virus, symptomatic or asymptomatic, and who were therefore assessed at the time of enrolment to be at appreciable risk of imminently developing COVID-19. Such individuals included, but were not limited to, those who shared a household, those living in institutional residences (military lodging, dormitories, etc.), health care workers, long-term care facility workers, and workers in occupational or industrial settings in which close contact is common.

AZD7442

AZD7442 is a combination of two LAABs - tixagevimab (AZD8895) and cilgavimab (AZD1061) - derived from B cells donated by convalescent patients after SARS-CoV-2 virus. Discovered by Vanderbilt University Medical Center and licensed to AstraZeneca in June 2020 (https://www.astrazeneca.com/media-centre/articles/2020/advancing-our-discovery-of-novel-coronavirus-neutralising-antibodies-against-covid-19.html), the human monoclonal antibodies bind to distinct sites on the SARS-CoV-2 spike protein[2] and were optimised by AstraZeneca with half-life extension and reduced Fc receptor binding. The half-life extension approximately triples the durability of its action compared to conventional antibodies and could afford six to 12 months of protection from COVID-19 following a single administration.[3-6] The reduced Fc receptor binding aims to minimise the risk of antibody-dependent enhancement of disease - a phenomenon in which virus-specific antibodies promote, rather than inhibit, infection and/or disease.[7]

AZD7442 is currently being tested in several additional COVID-19 prevention and treatment trials: PROVENT (https://www.c19proventstudy.com/#!/)[8] Phase III trial of over 5,000 participants in pre-exposure prophylaxis; TACKLE COVID-19 (https://www.tackle-covid-19.com/en-US/)[9] Phase III treatment trial in outpatient setting; and collaborator treatment trials in outpatient and hospitalised settings. AZD7442 is being assessed in both IM and intravenous administration routes.

AZD7442 is being developed with support from the US Government, including federal funds from the Department of Health and Human Services; Office of the Assistant Secretary for Preparedness and Response; Biomedical Advanced Research and Development Authority in partnership with the Department of Defense; Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense; under Contract No. W911QY-21-9-0001.

Preliminary `in vitro' findings from investigators at Oxford University and Columbia University also demonstrate that AZD7442 neutralises recent emergent SARS-CoV-2 viral variants.[10-14]

Data published in Nature (https://www.nature.com/articles/s41586-020-2548-6) in July 2020 showed that in pre-clinical experiments, the LAABs were able to block the binding of the SARS-CoV-2 virus to host cells and protect against infection in cell and animal models of disease.[15]

Under the terms of the licensing agreement with Vanderbilt, AstraZeneca will pay single-digit royalties on future net sales.

AstraZeneca

AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines in Oncology and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.

Contacts

For details on how to contact the Investor Relations Team, please click here (https://www.astrazeneca.com/investor-relations.html#Contacts). For Media contacts, click here (https://www.astrazeneca.com/media-centre/contacts.html).

References

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8. Clinicaltrials.gov. Phase III Double-blind, Placebo-controlled Study of AZD7442 for Pre-exposure Prophylaxis of COVID-19 in Adult. (PROVENT). Available at: https://clinicaltrials.gov/ct2/show//NCT04625725 (https://clinicaltrials.gov/ct2/show/NCT04625725). [Last accessed: 7 April 2021].
9. Clinicaltrials.gov. Phase III Study of AZD7442 for Treatment of COVID-19 in Outpatient Adults (TACKLE). Available at: https://clinicaltrials.gov/ct2/show//NCT04723394 (https://clinicaltrials.gov/ct2/show/NCT04723394). [Last accessed: 7 April 2021].
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