India Pharma Outlook Team | Monday, 17 April 2023
At the 33rd European Congress of Clinical Microbiology & Infectious Diseases (ECCMID), 15 - 18 April 2023, AstraZeneca will highlight new data across its vaccines and immune therapies portfolio, reinforcing its ambition to provide long-lasting immunity for millions of people worldwide. At the event, the company will present 15 abstracts, including four oral presentations. AZD3152, AstraZeneca's investigational long-acting Covid-19 antibody, as well as Evusheld (tixagevimab and cilgavimab), Vaxzevria (ChAdOx1-S [Recombinant], formerly AZD1222) in Covid-19, and Beyfortus (nirsevimab) in respiratory syncytial virus (RSV).
Additional information on AstraZeneca's expanding vaccines and immune therapies pipeline against a wide range of pathogens will be presented. "We are excited to share our data at ECCMID this year, reflecting the progress of our Vaccines and Immune Therapies portfolio and our ambition to deliver long-lasting immunity and protect against infectious diseases that affect millions of people around the world," said Iskra Reic, executive vice president, vaccines and immune therapies, AstraZeneca. Covid-19 is still a major concern, affecting the immunocompromised disproportionately.
Our initial in vitro data from our next generation long-acting antibody, AZD3152, show that it has the potential to protect immunocompromised patients from all known Covid-19 variants of concern." AstraZeneca will present the first in vitro neutralisation data on AZD3152, including activity against Covid-19 variants that were previously and are currently circulating. There will also be an update on the ongoing SUPERNOVA phase I/III trial evaluating AZD3152 for the prevention of symptomatic Covid-19 in an immunocompromised population.
Three abstracts from the phase IV VALOUR trial assessing Evusheld's real-world effectiveness in immunocompromised adults with mild-to-moderate Covid-19 will be presented, including new analyses on hospitalisation and death prevention. A 12-month analysis of data from the phase III PROVENT prophylaxis trial will also be presented. RSV is a common and highly contagious seasonal virus that infects nearly every child by the age of two. New data from the phase II MUSIC trial, which examined the safety profile and pharmacokinetics (PK) exposures in immunocompromised children aged less than two experiencing their first or second RSV season, will be presented as part of the ongoing Beyfortus clinical trial programme.
This study adds to the body of evidence supporting Beyfortus' consistent efficacy across endpoints and studies showing 70-80% efficacy against medically attended RSV Lower Respiratory Tract Disease (LRTD) vs placebo with a single dose. AstraZeneca will also present data on its Covid-19 vaccine Vaxzevria, which will assess vaccine-generated immunogenicity in the context of hybrid immunity from natural infection, which is becoming more common. AZD3152 is a next-generation long-acting antibody (LAAB) under investigation. In vitro studies have shown that AZD3152 has broad and potent neutralising activity against all known SARS-CoV-2 variants of concern. AZD3152 was created from B-cells donated by patients recovering from SARS-CoV-2 infection.
AZD3152 was optimised in the same way as Evusheld, with the same half-life extension, reduced Fc effector function, and complement C1q binding. The extended half-life is expected to provide six months of protection against Covid-19. The ongoing SUPERNOVA phase I/III trial is assessing the safety and neutralising activity of AZD3152 in adults and adolescents 12 years of age and older for the prevention of symptomatic Covid-19. Participants have immune impairment and may not mount an adequate protective response following Covid-19 vaccination, putting them at high risk of developing severe Covid-19 if infected. The trial is based on the established generalised safety and efficacy of Evusheld and employs a novel immunobridging approach to establish the safety and efficacy of AZD3152. AZD3152 is expected to be available in the second half of 2023, subject to regulatory approval and trial readouts. 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.
Evusheld is a combination of two long-acting antibodies derived from convalescent patients infected with SARS-CoV-2, tixagevimab (AZD8895) and cilgavimab (AZD1061). Human monoclonal antibodies discovered by Vanderbilt University Medical Centre and licenced to AstraZeneca in June 2020 bind to distinct sites on the SARS-CoV-2 spike protein19 and were optimised by AstraZeneca with half-life extension and reduction of Fc effector function and complement C1q binding. When compared to conventional antibodies, the half-life extension more than triples the durability of its action; data from the PROVENT phase III trial show protection lasting six months.
The reduced Fc effector function is intended to reduce the risk of antibody-dependent disease enhancement, which occurs when virus-specific antibodies promote, rather than inhibit, infection and/or disease. Evusheld is authorised in many countries around the world for both pre-exposure prophylaxis (prevention) and treatment of Covid-19. Beyfortus (nirsevimab) is a single-dose long-acting antibody developed and commercialised by AstraZeneca and Sanofi in collaboration using AstraZeneca's YTE technology. It is intended to protect infants entering or during their first respiratory syncytial virus (RSV) season, as well as children up to the age of 24 months who are susceptible to severe RSV disease during their second RSV season.
Beyfortus was created to provide newborns and infants with direct RSV protection via an antibody to help prevent RSV-caused Lower Respiratory Tract Infections (LRTI). Monoclonal antibodies do not require immune system activation to provide timely, rapid, and direct protection against disease. In November 2022, Beyfortus was approved by the European Commission and by the UK Medicines and Healthcare products Regulatory Agency (MHRA) for the prevention of RSV LRTI disease in newborns and infants from birth during their first RSV season. The recommended dose of Beyfortus is a single intramuscular injection of 50 mg for infants with body weight <5 kg and a single intramuscular injection of 100 mg for infants with body weight =5 kg. Beyfortus has also been granted regulatory designations to facilitate expedited development by several major regulatory agencies around the world.
These include Breakthrough Therapy Designation by the China Center for Drug Evaluation under the National Medical Products Administration;?Breakthrough Therapy Designation from the US Food and Drug Administration; access granted to the European Medicines Agency (EMA PRIority Medicines (PRIME) scheme; and 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). In March 2017, AstraZeneca and Sanofi announced an agreement to develop and commercialise nirsevimab. Under the terms of the agreement, AstraZeneca leads development and manufacturing activities, and Sanofi leads commercialisation activities and records revenue.
Under the terms of the global agreement, Sanofi made an upfront payment of €120m, has paid development milestones of €55m and will pay up to €440m further milestones subject to achievement of certain development and sales-related milestones. The two companies share ex-US costs and profits. Revenue from the agreement is reported as Alliance Revenue and Collaboration Revenue in the Company’s financial statements. Following a revision to the profit-sharing arrangement relating to the development and commercialisation of nirsevimab in the US between AstraZeneca, Sanofi and Sobi, Sobi has entered into a direct relationship with Sanofi, replacing the previous participation agreement with AstraZeneca entered into in November 2018. The University of Oxford invented the AstraZeneca Covid-19 vaccine. It employs a replication-deficient chimp viral vector based on a weakened version of a common cold virus (adenovirus) that causes infections in chimps and contains the SARS-CoV-2 virus spike protein's genetic material.
The surface spike protein is produced following vaccination, priming the immune system to attack the SARS-CoV-2 virus if it later infects the body. Vaxzevria is a ‘viral vector’ vaccine, which means a version of a virus that cannot cause disease is used as part of the vaccine, leaving the body knowing how to fight it if it is exposed to the real virus later. This vaccine technology has been used by scientists over the past 40 years to fight other infectious diseases such as the flu, Ebola, and HIV. Vaxzevria is estimated according to model outcomes to have helped save over six million lives in the first year of vaccination (8 December 2020 to 08 December 2021).
Vaxzevria is approved for Covid-19 primary vaccination schedule and first booster on top of a primary schedule in both homologous and heterologous settings, based on an acceptable risk-benefit profile. Under a sub-license agreement with AstraZeneca, the vaccine is manufactured and supplied by the Serum Institute of India under the name Covishield.
