16 May 2024
SUPERNOVA Phase III trial of
sipavibart long-acting antibody met primary endpoints in preventing
COVID-19 in immunocompromised patient population
Positive high-level results from the SUPERNOVA Phase
III COVID-19 pre-exposure prophylaxis (prevention) trial showed
AstraZeneca's sipavibart (formerly AZD3152), an investigational
long-acting antibody (LAAB), demonstrated a statistically
significant reduction in the incidence of
symptomatic COVID‑19 compared to
control (tixagevimab/cilgavimab or placebo) in an immunocompromised
patient population.
The trial met both dual primary
endpoints; the first one being the relative risk reduction
of symptomatic COVID-19 caused by any SARS-CoV-2 variant and
the second being the relative risk reduction of infections caused
by SARS-CoV-2 variants not containing the F456L mutation.
SUPERNOVA demonstrated the potential benefit of sipavibart in an
evolving variant landscape in which COVID-19 cases captured over
the course of the trial were caused by several different SARS-CoV-2
variants.
SUPERNOVA is a large Phase III global trial
providing the only efficacy data in immunocompromised
patients, demonstrating the potential benefit of a COVID-19
antibody against recent SARS-CoV-2 variants. Immunocompromised
patients include those with blood cancer, organ transplant
recipients, patients with end-stage renal disease requiring
dialysis, patients receiving B-cell depleting therapy within the
past year, and those taking immunosuppressive medications. Despite
accounting for approximately 4% of the population,
immunocompromised patients make up about 25% of COVID-19
hospitalisations, ICU admissions, and deaths, even after multiple
doses of COVID-19 vaccines.1-6
Ghady Haidar, M.D., UPMC
(University of Pittsburgh Medical Center) transplant
infectious diseases physician, medical director of the
translational research program at UPMC's division of infectious
diseases and SUPERNOVA trial primary investigator, said: "COVID-19
still represents a significant and disproportionate risk for
immunocompromised patients, with infection often leading to serious
and protracted illness. By delivering infection-fighting antibodies
directly to patients who often don't respond adequately to
vaccines, the data support that sipavibart has the potential to
provide much-needed protection against COVID-19 in this highly
vulnerable population."
Iskra Reic, Executive Vice President, Vaccines and
Immune Therapies, AstraZeneca, said: "Immunocompromised patients
currently have limited or no options for COVID-19 protection and
continue to face a significant burden of disease, despite often
being fully vaccinated. Sipavibart has the potential to prevent
COVID-19 in the immunocompromised and we will now work with
regulatory authorities globally to bring sipavibart to these
vulnerable patients."
Sipavibart was well tolerated in the trial and
preliminary analyses show adverse events were balanced
between the control and sipavibart arms.
The data will be presented at a forthcoming medical
meeting. AstraZeneca is in dialogue with regulatory authorities on
potential authorisation or approval pathways.
Notes
SUPERNOVA
SUPERNOVA is a Phase III, global, randomised,
double-blind, placebo-controlled trial assessing the safety and
efficacy of sipavibart compared to control (tixagevimab/cilgavimab
or placebo) for the prevention of COVID-19. The trial was conducted
at 197 sites in the US, UK, EU and Asia. Participants were
randomised in a 1:1 ratio to receive either a 300mg intramuscular
dose of sipavibart or comparator, with 1,669/3,335 participants
receiving sipavibart and 1,666/3,335 receiving comparator. A second
dose of sipavibart or comparator was given approximately six months
after initial receipt of study product.
The trial had dual primary efficacy endpoints. The
first evaluated the efficacy of sipavibart against any confirmed
SARS-CoV-2 positive symptomatic illness occurring post dose prior
to day 181 caused by any variant (i.e., all cases regardless of if
the variant has the F456L mutation or not, which sipavibart is not
expected to neutralise). The second dual primary efficacy analysis
was conducted using only the confirmed COVID-19 cases in the trial
where the variant causing the COVID-19 cases did not have the F456L
mutation, referred to as a "matched" variant analysis.
Participants were individuals 12 years of age and
over who would benefit from prevention with the investigational
LAAB, defined as having increased risk for inadequate response to
active immunisation (predicted poor responders to vaccines or
intolerant of vaccine). Participants at the time of screening had a
negative point-of-care SARS-CoV-2 serology test. Participants will
be followed for 15 months, with SARS-CoV-2 neutralising antibodies
assessed at one, three and six months.
All participants in the trial had an
immunocompromising condition and/or were on immunosuppressive
treatments, which put them at risk to mount an inadequate immune
response to vaccination and at high risk of developing severe
COVID-19. This included patients with hematologic malignancies,
solid organ transplant recipients, hematopoietic stem cell
transplants, end stage kidney disease/dialysis and being within one
year of receipt of B cell depleting therapy, among others.
Across the treatment groups, demographic and
baseline characteristics were generally well balanced.
Sipavibart
Sipavibart (formerly AZD3152) is an investigational
long-acting monoclonal antibody (LAAB) against COVID-19. Sipavibart
was designed to provide broad and potent coverage across Omicron
and ancestral viral variants by neutralising spike protein
interaction with the host receptor ACE2.7
Sipavibart was derived from B-cells donated by
convalescent patients after SARS-CoV-2 infection. Sipavibart has
been engineered using the same antibody scaffold as Evusheld and was optimised with the
same half-life extension and reduced Fc effector function and
complement C1q binding platform.7 The reduced Fc
effector function 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.
Sipavibart was licensed by AstraZeneca in
May 2022 from RQ Biotechnology.
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, Rare Diseases, 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 Social Media @AstraZeneca.
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References
1. Evans RA et al.
Impact of COVID-19 on Immunocompromised Populations during the
Omicron Era: Insights from the Observational Population-Based
INFORM Study. The Lancet Regional
Health - Europe. 2023;0(0):100747.
doi:10.1016/J.LANEPE.2023.100747
2. Dube S. Continued
Increased Risk of COVID-19 Hospitalisation and Death in
Immunocompromised Individuals Despite Receipt of ≥4 Vaccine Doses:
Updated 2023 Results from INFORM, a Retrospective Health Database
Study in England. Poster P0409 at ECCMID 2024.
3. Turtle L. Individuals
with Multiple Sclerosis Are at High Risk for COVID-19
Hospitalisation and Death Despite High Rates of Vaccination:
Results from the England INFORM Study. Oral Presentation at ECCMID
2024.
4. Meeraus W. High
Prevalence of Immunocompromising Conditions Among Patients with
Severe Acute Respiratory Infection, Including SARS-CoV-2: Results
from a Multicentre, Test-Negative Case Control Study. Abstract
#01796 at ECCMID 2024.
5. Meeraus W.
Immunocompromise, Cancer and Other Comorbidities in Patients with
Severe Acute Respiratory Infection Testing Positive Versus Negative
for SARS-CoV-2: A Post Hoc Analysis of COVIDRIVE Data from May 2021
to May 2023. Abstract #01800 at ECCMID 2024.
6. Ketkar A et al.
Assessing the Risk and Costs of COVID-19 in Immunocompromised
Populations in a Large United States Commercial Insurance Health
Plan: The EPOCH-US Study. Curr
Med Res Opin. 2023. 39 (8):1103-1118.
7. Francica JR, Cai Y,
Diallo S, et al. 1355. The SARS-CoV-2 Monoclonal Antibody AZD3152
Potently Neutralizes Historical and Emerging Variants and is Being
Developed for the Prevention and Treatment of COVID-19 in High-risk
Individuals. Open Forum Infect
Dis. 2023 Nov 27;10(Suppl 2):ofad500.1192. doi:
10.1093/ofid/ofad500.1192.
Adrian
Kemp
Company
Secretary
AstraZeneca
PLC