Oxford University breakthrough on global COVID-19 23RD NOV 2020

The University of , in collaboration with AstraZeneca plc, today announces interim trial data from its Phase III trials that show its candidate coronavirus vaccine, ChAdOx1 nCoV- 2019, is effective at preventing COVID-19 (SARS-CoV-2) and offers a high level of protection.

➢ Phase 3 interim analysis including 131 Covid-19 cases indicates that the vaccine is 70.4% effective when combining data from two dosing regimens ➢ In the two different dose regimens vaccine efficacy was 90% in one and 62% in the other ➢ Higher efficacy regimen used a halved first dose and standard second dose ➢ Early indication that vaccine could reduce virus transmission from an observed reduction in asymptomatic ➢ There were no hospitalised or severe cases in anyone who received the vaccine ➢ Large safety database from over 24,000 volunteers from clinical trials in the UK, Brazil and South Africa, with follow up since April ➢ Crucially, vaccine can be easily administered in existing healthcare systems, stored at ‘fridge temperature’ (2-8 °C) and distributed using existing logistics ➢ Large scale manufacturing ongoing in over 10 countries to support equitable global access

Professor Andrew Pollard, Director of the Oxford Vaccine Group and Chief Investigator of the Oxford Vaccine Trial, said: ‘The announcement today takes us another step closer to the time when we can use to bring an end to the devastation caused by SARS-CoV-2. We will continue to work to provide the detailed information to regulators. It has been a privilege to be part of this multi-national effort which will reap benefits for the whole world.’

Following the trial reaching the target for interim analysis, the independent Data and Safety Monitoring Board (DSMB) recommended that the team at Oxford conduct its first analysis on all the cases with data locked on 4 November 2020.

These preliminary data indicate that the vaccine is 70.4% effective, with tests on two different dose regimens showing that the vaccine was 90% effective if administered at a half dose and then at a full dose, or 62% effective if administered in two full doses.

Additional cases are expected to accrue by the time of the final analysis and future analyses will determine the duration of protection. No serious safety events related to the vaccine have been identified.

Oxford will now support AstraZeneca in submitting both the interim Phase III efficacy data and the extensive safety data to all regulators across the world, including in the UK, Europe and Brazil for independent scrutiny and product approval, including for emergency use. Many of these regulators have been reviewing the trial data on a rolling basis during the trial. In parallel, Oxford is submitting the full analysis of the Phase III interim data for independent scientific peer review and publication. The coordination of the programme and execution of the trials in the UK would not have been possible without the support of the National Institute for Health Research and UKRI.

These data also suggest that this half dose and full dose regimen could help to prevent transmission of the virus, evidenced by lower rates of asymptomatic in the vaccinees, with further information to become available when trial data are next evaluated.

The interim Phase III data builds on Oxford’s phase I/II peer-reviewed trial results which have shown that the vaccine induces strong antibody and T cell immune responses across all age groups, including older adults, and has a good safety profile.

The clinical trials, enrolling over 24,000 participants from diverse racial and geographical groups in the UK, Brazil and South Africa, will now continue to final analysis. Further trials are being conducted in the United States, Kenya, Japan and India and the trial team expect to have under 60,000 participants by the end of the year. These trials will provide regulators with further information about the efficacy and safety of the Oxford candidate vaccine, including its ability to both protect against and stop the transmission of COVID-19.

The Oxford vaccine (ChAdOx1 nCoV-19) is made from a virus, which is a weakened version of a common cold virus (adenovirus), that has been genetically changed so that it is impossible for it to grow in humans.

Adenovirus vaccines have been researched and used extensively for decades and have the significant benefit that they are stable, easily manufactured, transported and stored at domestic fridge temperature (2-8 degrees C). This means they can be easily distributed using existing medical facilities such as doctor’s surgeries and local pharmacies, allowing for the vaccine, if approved, to be deployed very rapidly.

Oxford University’s collaboration with AstraZeneca has been crucial to the successful development of the vaccine and vital for its global manufacturing and distribution across the world. AstraZeneca already has international agreements in place to supply three billion doses of the vaccine, with access being built through more than 30 supply agreements and partner networks.

A key element of Oxford’s partnership with AstraZeneca is the joint commitment to provide the vaccine on a not-for-profit basis for the duration of the pandemic across the world, and in perpetuity to low- and middle-income countries.

Professor , Vice-Chancellor at the , said: ‘This is a great day for the University of Oxford and for universities everywhere. Pushing at the frontiers of knowledge with partners across the globe and putting our extraordinary brainpower in service to society, is what we do best.’

Pascal Soriot, Chief Executive Officer, AstraZeneca, said: ‘Today marks an important milestone in our fight against the pandemic. This vaccine’s efficacy and safety confirm that it will be highly effective against COVID-19 and will have an immediate impact on this public health emergency. Furthermore, the vaccine’s simple supply chain and our no-profit pledge and commitment to broad, equitable and timely access means it will be affordable and globally available supplying hundreds of millions of doses on approval.’

Close up of syringe and vaccine vial

COVID-19 vaccination programme This guidance provides detail about what the CVP (COVID-19 vaccination programme) service in England involves, what is expected of practices, what you will get to support this work, and guidance on what to do now. Updated: Tuesday 17 November 2020

The BMA GP committee England and NHSEI have agreed an ES (enhanced service), directed by NHSEI, for general practice in England to lead the delivery of the CVP (COVID- 19 vaccination programme).

As an ES directed by NHSEI, it will be optional for practices to sign up to the service.

The intention is to prepare for a service to be delivered from 1 December, however the actual start date will depend on the availability of vaccines.

Similarly, we expect vaccine availability to be limited to begin with, meaning only small numbers of vaccine may be given in December and most vaccinations taking place in early 2021, giving practices more time to prepare.

What the service involves

At present, based on the information currently known to us, the vaccines being developed require two doses per patient, with a 21-28 day gap between doses.

Eligible patients will be confirmed soon, but are expected to be in line with the latest JCVI (joint committee on vaccination and immunisation) recommendations.

Similar to the flu groups, they include: ➢ all over the age of 50 ➢ those at high risk ➢ care home residents and staff ➢ all health and care workers (although it is unlikely that general practice will be required to deliver to all health and care staff who may get it from their employer).

The high priority groups will be vaccinated first, and as the vaccine becomes more available, practices will be able to provide this to increasing numbers.

The ES includes provision of vaccinations to housebound patients via home visits, as well as staff and residents of care homes. Community service providers will be expected to play a role in this service, particularly with housebound patients, as many do with flu immunisations using practice stocks.

Practices will be able to vaccinate their own staff and be paid for doing so.

Alongside the general practice-led service, other providers (likely to be NHS trusts) will be commissioned to provide the programme through other means, probably via regional vaccination centres in a similar way to the testing centres.

Local pharmacies may be commissioned where general practice coverage is not enough.

National and local public campaigns will advertise the services on offer, and which patients are eligible.

How the service will operate

Due to the logistics of delivery and characteristics of the vaccines, the service needs to be delivered at scale. The current assumption is that it will need to be done through groups of practices working together (likely along PCN (primary care network) geographies), with one designated vaccination site (ideally to be a GP practice). That would be determined by the practices involved.

As vaccines become more widely available it is possible that more than one site could be possible within each grouping.

Working together, practices will need to be prepared to offer vaccinations seven days a week so that the vaccine is delivered within its short shelf-life and so patients receive it as soon as possible. Specifics around delivery of the service will depend on matching patient demand and vaccine availability.

Call and recall system

A national call and recall system will be used, in addition to practices operating their own call and recall systems if they wish to do so.

Patients can choose to attend either their local general practice-led designated site, or a regional immunisation service. If patients choose the local site, practices will need to contact patients to book an appropriate time. Practices will be able to use the national booking system instead of their local booking system if they choose.

Administering the vaccine

A registered healthcare professional will need to carry out the clinical assessment and consent. A suitably trained non-registered member of staff will be able to administer the vaccine itself under clinical supervision.

This could include staff from the relevant practices, from the PCN, as well as volunteers and other NHS staff – as decided by the relevant practices. There is an expectation that staff will be required to undertake appropriate training in advance. Other staff assisting in an administrative capacity would not be required to undertake the training, but an information pack will be provided.

It will be for practices to determine how they work together to deliver the programme. For instance, practices could operate a rota using their teams to immunise their own registered patients in different sessions during the week. Or, they may wish to employ a dedicated team to do this on behalf of all practices, or for some practices to act on behalf of others.

The latest information on the vaccines suggests that patients do not need to be observed following administration of the vaccine, but patients must not drive for 15 minutes after.

Patients would need to be contacted again to book in their second appointment (or this could be done at the time of administering the first) allowing for the appropriate gap. Patients will need to receive the second dose from the same provider.

Safety and risk

The vaccines will be going through testing procedures and MHRA (medicines and healthcare products regulatory agency) licencing process.

Confirmation of the specific vaccines will be given following completion of trials and licencing/approval.

The JCVI and others will provide independent input and decisions will be made in the normal way. If the vaccine is not approved through the rigorous approvals process, then there will not be a programme. The NHS and practices must be prepared for rapid delivery in the event that the vaccine is approved.

The Government previously released the outcome of the human medicines regulations consultation. This outlines that the Government will be liable for any adverse implications from a vaccine being put into supply (both immediately and into the future).

Commissioning as an enhanced service ensures that all individuals delivering the services will have indemnity under the clinical negligence scheme for general practice.

The vaccines and their characteristics

At present, we understand there are two vaccines likely to be supplied in the UK initially. As these and other vaccines are developed and tested their characteristics might change. The Pfizer vaccine & The AstraZeneca vaccine

Independent report JCVI: updated interim advice on priority groups for COVID-19 vaccination Published 25 September 2020 https://www.gov.uk/government/publications/priority-groups-for-coronavirus-covid-19-vaccination-advice-from-the-jcvi-25-september- 2020/jcvi-updated-interim-advice-on-priority-groups-for-covid-19-vaccination#fnref:2

Vaccine priority groups: interim advice

Based on the information provided, the committee agreed that it was not possible to come to a firm position on priority groups at this time. This provisional prioritisation for COVID-19 vaccines is based on preliminary information on the vaccines in development, and provisional timelines for vaccine availability, and is subject to change. This advice assumes availability of a vaccine which is safe and effective in all age groups and has a moderate impact on transmission.

The committee strongly agree that a simple age-based programme will likely result in faster delivery and better uptake in those at the highest risk.

Whether health and social care workers should be prioritised above, alongside, or below, persons at highest risk from COVID-19 would depend on the characteristics of the vaccines when they become available and the of disease at the time of delivery.

This interim ranking of priorities is a combination of clinical risk stratification and an age- based approach, which should optimise both targeting and deliverability. A provisional ranking of prioritisation for persons at-risk is set out below: 1) older adults’ resident in a care home and care home workers 2) all those 80 years of age and over and health and social care workers 3) all those 75 years of age and over 4) all those 70 years of age and over 5) all those 65 years of age and over 6) high-risk adults under 65 years of age 7) moderate-risk adults under 65 years of age 8) all those 60 years of age and over 9) all those 55 years of age and over 10) all those 50 years of age and over 11) rest of the population (priority to be determined) - A risk-benefit assessment would likely be undertaken in advising on vaccination The prioritisation could change substantially if the first available vaccines were not considered suitable for, or effective in, older adults.