AstraZeneca reinforces commitment to protecting the most vulnerable from serious infectious diseases at IDWeek 2023

Real-world data from INFORM study demonstrate increased risk of severe COVID-19 outcomes among all individuals with immunocompromising conditions and highlight need for additional protection

FLUMIST QUADRIVALENT data support the potential for a self-administered influenza vaccine to expand access to an important tool for prevention

AstraZeneca will showcase new preclinical, clinical and real-world data across its Vaccines & Immune Therapies portfolio at the 12th annual IDWeek conference October 11-15, reinforcing the important role of long-acting antibodies and vaccines to protect at-risk individuals from the increased burdens of common infectious respiratory diseases. The company will present 15 abstracts at the event, featuring three oral presentations, including one late-breaking oral, and 12 poster presentations.

Data will be presented featuring:

• Real-world evidence demonstrating the continued and disproportionate burden of COVID-19 on immunocompromised individuals
• BEYFORTUS (nirsevimab), a long-acting antibody for prevention of disease due to respiratory syncytial virus (RSV)
• Self-administration of the FLUMIST QUADRIVALENT intranasal influenza vaccine, a potential new option for expanding access to a seasonal influenza vaccine
• AZD3152, an investigational long-acting antibody against COVID-19

Iskra Reic, Executive Vice President of Vaccines & Immune Therapies, AstraZeneca, said: "Our ambition is to provide long-lasting immunity to millions of people where the burden of disease is greatest. This year at IDWeek, our data provide the strongest evidence to date that the burden of COVID-19 on those who are immunocompromised remains significant and disproportionate. In addition, we’ll share updated data on AZD3152 and BEYFORTUS and the important role these long-acting antibodies can play in preventing COVID-19 and RSV among the most vulnerable patients, ensuring that no one is left behind.”

Continued evidence on the importance of passive immunization as an approach to protect immunocompromised individuals

AstraZeneca will present updated in vitro neutralization data for the investigational long-acting antibody AZD3152 against historical and emerging COVID-19 variants.¹ Additionally, updated data on BEYFORTUS, a long-acting antibody recently approved by the US Food and Drug Administration (FDA) for the prevention of RSV lower respiratory tract disease (LRTD) in infants, will be presented, reinforcing BEYFORTUS as an important and differentiated intervention to provide protection for the most at-risk babies.^2-6 Passive immunization provides infection-fighting antibodies directly to immunocompromised patients who are unlikely to elicit an adequate immune response to traditional vaccinations.⁷

Real-world data highlight continued unmet need and disproportionate impact of COVID-19 for the immunocompromised

Three presentations, including two orals, from the groundbreaking INFORM real-world evidence study in England reveal the increased burden of severe COVID-19 outcomes facing all individuals with immunocompromised conditions compared to the general population, even when fully vaccinated against the virus, and highlight the need for additional protection to target this population.^8,9 The data also examine the increased risk for people with specific immunocompromising conditions, such as solid and haematologic malignancies, solid organ transplant and end-stage renal disease.¹⁰

Pioneering new ways to protect against influenza

AstraZeneca will present a summary of the evidence supporting the potential of self-administration of FLUMIST, its intranasal, injection-free, live attenuated influenza vaccine (LAIV). The study evaluates the potential for self- and caregiver-administered LAIV to enable more equitable access to the influenza vaccine for communities which lack easy access, thereby helping to meet vaccination targets.¹¹

Key AstraZeneca presentations during IDWeek 2023:

BEYFORTUS IMPORTANT SAFETY INFORMATION

Your child should not take BEYFORTUS if your child has a history of serious allergic reactions to nirsevimab-alip or any of the ingredients in BEYFORTUS.

Before your child receives BEYFORTUS, tell your healthcare provider about all of your child’s medical conditions, including if your child:

• has ever had a reaction to BEYFORTUS.
• has bleeding or bruising problems. If your child has a problem with bleeding or bruises easily, an injection could cause a problem.

Tell your healthcare provider about all the medicines your child takes, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Your infant should not receive a medicine called palivizumab if they have already received BEYFORTUS in the same RSV season.

Serious allergic reactions have happened with other medicines like BEYFORTUS. Get medical help right away if your child has any of the following signs or symptoms of a serious allergic reaction:

• swelling of the face, mouth, or tongue
• difficulty swallowing or breathing
• unresponsiveness
• bluish color of skin, lips, or under fingernails
• muscle weakness
• severe rash, hives, or itching

The most common side effects of BEYFORTUS include rash and pain, swelling, or hardness at the site of your child’s injection. These are not all the possible side effects of BEYFORTUS. Call your healthcare provider if you have questions about side effects.

Please see full Prescribing Information, including Patient Information, for more details.

FLUMIST QUADRIVALENT IMPORTANT SAFETY INFORMATION

• You should not get FLUMIST QUADRIVALENT if you have a severe allergy to eggs or to any inactive ingredient in the vaccine; have ever had a life-threatening reaction to influenza vaccinations; or are 2 through 17 years old and take aspirin or medicines containing aspirin – children or adolescents should not be given aspirin for 4 weeks after getting FLUMIST QUADRIVALENT unless your healthcare provider tells you otherwise.
• Children under 2 years old have an increased risk of wheezing (difficulty with breathing) after getting FLUMIST QUADRIVALENT.
• Tell your healthcare provider if you or your child are currently wheezing; have a history of wheezing if under 5 years old; have had Guillain-Barré syndrome; have a weakened immune system or live with someone who has a severely weakened immune system; have problems with your heart, kidneys, or lungs; have diabetes; are pregnant or nursing; or are taking a medication used to treat influenza like Tamiflu^®*, Relenza^®*, amantadine, or rimantadine.
• The most common side effects are runny or stuffy nose, sore throat, and fever over 100°F.

Approved Use

FLUMIST QUADRIVALENT is a vaccine that is sprayed into the nose to help protect against influenza. It can be used in people 2 through 49 years old. FLUMIST QUADRIVALENT may not prevent influenza in everyone who gets vaccinated.

Please see full Prescribing Information, including Patient Information.

*Tamiflu and Relenza are registered trademarks of their respective owners.

You may report side effects related to AstraZeneca products. 

EVUSHELD IMPORTANT SAFETY INFORMATION

Important Update:
On January 26th, 2023, the U.S. Food and Drug Administration (FDA) revised the Emergency Use Authorization (EUA) for EVUSHELD to limit its use to when the combined frequency of non-susceptible SARS-CoV-2 variants nationally is less than or equal to 90%. Based on this revision, EVUSHELD is not currently authorized for use in the U.S. until further notice by the Agency.

The U.S. Government recommends that facilities and providers with unexpired EVUSHELD retain all product in the event that SARS-CoV-2 variants which are neutralized by EVUSHELD become more prevalent in the U.S. in the future.

Please refer to the HHS website for expiry extension information.

CONTRADICATIONS

EVUSHELD is contraindicated in individuals with previous severe hypersensitivity reactions, including anaphylaxis, to EVUSHELD.

WARNINGS AND PRECAUTIONS

Hypersensitivity Including Anaphylaxis

Serious hypersensitivity reactions, including anaphylaxis, have been observed with EVUSHELD. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue administration and initiate appropriate medications and/or supportive therapy. Clinically monitor individuals after injections and observe for at least 1 hour.

Risk of Cross-Hypersensitivity with COVID-19 Vaccines

Risk of cross-hypersensitivity with COVID-19 vaccines exist as EVUSHELD contains polysorbate 80, which is in some COVID-19 vaccines and is structurally similar to polyethylene glycol (PEG), an ingredient in other COVID-19 vaccines.

Risk for COVID-19 Due to SARS-CoV-2 Viral Variants Not Neutralized by EVUSHELD

Certain SARS-CoV-2 viral variants may not be neutralized by EVUSHELD. Inform individuals of the increased risk, compared to other variants, for COVID-19 due to SARS-CoV-2 viral variants not neutralized by EVUSHELD. If signs and symptoms of COVID-19 occur, advise individuals to test for COVID-19 and seek medical attention, including starting treatment for COVID-19 as appropriate.

Clinically Significant Bleeding Disorders

As with any other intramuscular injection, EVUSHELD should be given with caution to individuals with thrombocytopenia or any coagulation disorder.

Cardiovascular Events

A higher proportion of subjects who received EVUSHELD versus placebo reported myocardial infarction and cardiac failure serious adverse events. All of the subjects with events had cardiac risk factors and/or a prior history of cardiovascular disease at baseline. A causal relationship between EVUSHELD and these events has not been established.

ADVERSE REACTIONS

The most common adverse events are headache, fatigue and cough.

USE IN SPECIFIC POPULATIONS

Pregnancy

There are insufficient data to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. EVUSHELD should only be used during pregnancy if the potential benefit outweighs the potential risk for the mother and the fetus.

Lactation

There are no available data on the presence of tixagevimab or cilgavimab in human milk or animal milk, the effects on the breastfed infant, or the effects of the drug on milk production. Maternal IgG is known to be present in human milk.

Pediatric Use

EVUSHELD is not authorized for use in pediatric individuals under 12 years of age or weighing less than 40 kg. The safety and effectiveness of EVUSHELD have not been established in pediatric individuals.

AUTHORIZED USE FOR EVUSHELD

EVUSHELD is authorized for use under an EUA for the pre-exposure prophylaxis of COVID-19 in adults and pediatric individuals (12 years of age and older weighing at least 40 kg):

• Who are not currently infected with SARS-CoV-2 and who have not had a known recent exposure to an individual infected with SARS-CoV-2 and
  • Who have moderate to severe immune compromise due to a medical condition or receipt of immunosuppressive medications or treatments and may not mount an adequate immune response to COVID-19 vaccination or
  • For whom vaccination with any available COVID-19 vaccine, according to the approved or authorized schedule, is not recommended due to a history of severe adverse reaction to a COVID-19 vaccine(s) and/or COVID-19 vaccine component(s).

EVUSHELD may only be prescribed for an individual patient by physicians, advanced practice registered nurses, and physician assistants that are licensed or authorized under state law to prescribe drugs in the therapeutic class to which EVUSHELD belongs (i.e., anti-infectives).

EVUSHELD has been authorized by FDA for the emergency use described above.

EVUSHELD is not FDA-approved for any use, including use for pre-exposure prophylaxis of COVID-19.

EVUSHELD is authorized only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of EVUSHELD under section 564(b)(1) of the Act, 21 U.S.C. § 360bbb-3(b)(1), unless the authorization is terminated or revoked sooner.

LIMITATIONS OF AUTHORIZED USE

• EVUSHELD is not authorized for use in individuals:
  • For treatment of COVID-19, or
  • For post-exposure prophylaxis of COVID-19 in individuals who have been exposed to someone infected with SARS-CoV-2
• EVUSHELD is authorized for use only when the combined frequency of non-susceptible variants nationally is less than or equal to 90%, based on available information including variant susceptibility to EVUSHELD and national variant frequencies
• Pre-exposure prophylaxis with EVUSHELD is not a substitute for vaccination in individuals for whom COVID-19 vaccination is recommended. Individuals for whom COVID-19 vaccination is recommended, including individuals with moderate to severe immune compromise who may derive benefit from COVID-19 vaccination, should receive COVID-19 vaccination.
• In individuals who have received a COVID-19 vaccine, EVUSHELD should be administered at least two weeks after vacccination

Please see the Fact Sheet for Healthcare Providers and Fact Sheet for Patients, Parents and Caregivers.

Under the EUA, all serious adverse events and medication errors potentially related to EVUSHELD use must be reported within 7 calendar days from the healthcare provider’s awareness of the event.

Serious adverse event reports and medication error reports should be submitted to FDA’s MedWatch program by:

• Completing and submitting the form online
• Completing and submitting a postage-paid FDA Form 3500 and returning by:
• Mail (MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787) or
• Fax (1-800-FDA-0178) or
• Contacting the FDA at 1-800-FDA-1088 to request a reporting form.

In addition, please fax a copy of all FDA MedWatch forms to AstraZeneca at 1-866-742-7984.

You may report side effects related to AstraZeneca products by clicking here.

Notes

AZD3152
AZD3152 is an investigational next-generation long-acting antibody (LAAB). AZD3152 has been shown in in vitro studies to have broad and potent neutralising activity across a range of historical and contemporary SARS-CoV-2 variants.¹ AZD3152 binds to a highly conserved area on the SARS-CoV-2 spike protein.¹²

AZD3152 was derived from B-cells donated by convalescent patients after SARS-CoV-2 infection. AZD3152 was optimised with the same half-life extension and reduced Fc effector function and complement C1q binding platform as Evusheld. The extended half-life is expected to confer protection from COVID-19 for six months.¹² 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.¹³

AstraZeneca licensed AZD3152 from RQ Biotechnology in May 2022. Under the licensing agreement, RQ Bio is eligible to receive single digit royalties on sales in addition to potential milestone payments.

AZD3152 is being investigated in the ongoing SUPERNOVA Phase III COVID-19 prevention trial and is anticipated to be available as early as H2 2023, subject to regulatory reviews and trial readouts.

FLUMIST QUADRIVALENT
FLUMIST QUADRIVALENT is a quadrivalent live attenuated influenza vaccine (LAIV), which is administered as a nasal spray for the prevention of influenza. FLUMIST QUADRIVALENT is an Advisory Committee on Immunization Practices (ACIP) and American Academy of Pediatrics (AAP) recommended flu vaccine option. FLUMIST QUADRIVALENT was originally approved in the US in 2003 and since then almost 200 million doses have been distributed around the world. 

BEYFORTUS
BEYFORTUS (nirsevimab) is a single dose long-acting antibody, developed and commercialised in partnership by AstraZeneca and Sanofi using AstraZeneca’s YTE technology. It is designed to protect infants born during or entering their first RSV season and for children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season. BEYFORTUS, provided directly to newborns and infants as a single dose, offers rapid protection via an antibody to help prevent LRTD caused by RSV, without requiring activation of the immune system. BEYFORTUS administration can be timed to the start of the RSV season.⁷

BEYFORTUS is currently approved for use in the US, EU, Great Britain and Canada and has been granted regulatory designations to facilitate expedited development by several major regulatory agencies around the world. These include Breakthrough Therapy Designation and Priority Review Designation by the China Center for Drug Evaluation under the National Medical Products Administration and being named “a medicine for prioritized development” under the Project for Drug Selection to Promote New Drug Development in Pediatrics by the Japan Agency for Medical Research and Development (AMED), further leveraging Breakthrough Therapy Designation in the US and access granted to the European Medicines Agency (EMA PRIority MEdicines (PRIME) scheme.

AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialization 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  www.astrazeneca-us.com and follow us on social media @AstraZeneca.

Contacts

Brendan McEvoy        +1 302 885 2677
Jillian Gonzales          +1 302 885 2677       

US Media Mailbox: usmediateam@astrazeneca.com           

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References

1. Francica J et al. 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. Poster 1355. 12th Annual IDWeek Conference (2023)
2. Wilkins D, et al. Nirsevimab is Associated with Higher and More Sustained RSV Neutralizing Antibody Responses Compared with Standard of Care Palivizumab: Observations from a 2:1 Randomized, Phase 2/3 Trial in Medically Vulnerable Children (MEDLEY). Oral presentation 1934 at 12th Annual IDWeek Conference (2023)
3. Hammitt LL et al. Nirsevimab for Prevention of RSV in Healthy Late-Preterm and Term Infants. New England Journal of Medicine. 2022;386(9):837-846
4. A Study to Evaluate the Safety and Efficacy of MEDI8897 for the Prevention of Medically Attended RSV LRTI in Healthy Preterm Infants. Study Results. ClinicalTrials.Gov. https://clinicaltrials.gov/ct2/show/results/NCT02878330 [Last accessed: October 2023]
5. Griffin MP et al. Single-Dose Nirsevimab for Prevention of RSV in Preterm Infants. New England Journal of Medicine. 2020;383(5):415-425
6. Simões EAF et al. Efficacy of Nirsevimab against Respiratory Syncytial Virus Lower Respiratory Tract Infections in Preterm and Term Infants, and Pharmacokinetic Extrapolation to Infants with Congenital Heart Disease and Chronic Lung Disease: A Pooled Analysis of Randomised Controlled Trials. Lancet Child Adolesc Health. 2023;7(3):180-189
7. Centers for Disease Control and Prevention. Immunity Types. Published online 2021. https://www.cdc.gov/vaccines/vac-gen/immunity-types.htm [Last accessed: October 2023]
8. Dube S et al. Increased Risk of COVID-19 Hospitalization and Death in Vaccinated Patients with End-Stage Renal Disease and Dialysis: Initial Results from INFORM, a Retrospective Health Database Observational Study in England. Oral presentation 1095 at 12th Annual IDWeek Conference (2023)
9. Dube S et al. Fully Vaccinated Individuals with Immunocompromised Conditions Are Still at Increased Risk of Severe COVID-19 Outcomes from the Omicron Variant: Initial Results from INFORM, a Retrospective Health Database Observational Study in England. Oral presentation 1096 at 12th Annual IDWeek Conference (2023)
10. McNulty R et al. Increased Risk of Severe COVID-19 Outcomes Across All Groups of Individuals with Hematological Malignancies, Solid Tumors, and Solid Organ Transplants Compared with the General Population: Initial Results from INFORM, a Retrospective Health Database Observational Study in England. Poster 398. 12th Annual IDWeek Conference (2023)
11. Jhaveri R et al. Home Administration of Intranasal Live Attenuated Influenza Vaccine: A Review of Current Evidence and Potential for Meeting Vaccination Targets. Poster 2610. 12th Annual IDWeek Conference (2023) 
12. AstraZeneca Data on File REF-173312
13. Van Erp EA et al. Fc-Mediated Antibody Effector Functions During Respiratory Syncytial Virus Infection and Disease. Front Immunol. 2019;10(MAR)