UCLH and Crick research influence new national treatment guidelines for COVID-19

Research from UCLH and the Francis Crick Institute was key to the development of important new Covid-19 treatment guidelines announced last week.

The final draft guidance published by NICE on the treatment of patients at high risk from Covid-19 recommends use of the therapeutic antibody sotrovimab.

There had been a risk that treatment with sotrovimab may no longer be available – but research done by investigators in the Legacy study led by UCLH consultant Dr Emma Wall and Crick Virologist Dr David Bauer highlighted the continuing efficacy of the treatment.

The team were able to do this research thanks to UCLH clinical expertise and state-of-the-art facilities housed at the Crick – and at a time when clinical trials involving sotrovimab were becoming increasingly difficult.

Inclusion of sotrovimab in the NICE guidance will mean high-risk patients are still able to receive a treatment which can offer protection against Covid-19.

Development of sotrovimab

Sotrovimab is a type of drug known as a monoclonal antibody, and it was one of the first treatments of its kind to be licensed for the treatment of Covid-19.

Anti-viral therapies such as sotrovimab were rapidly developed in 2020-21 in parallel with vaccines. Other drugs that were developed included molnupiravir and paxlovid – though these drugs are not antibody treatments.

While vaccination can protect most people from severe Covid-19, some people have a poorer response to vaccination, including some older adults, people with significant existing health conditions, and immunocompromised people. There are over two million people in the UK alone in these groups.

Anti-viral therapies work by acting in the blood of patients to stop the virus getting into cells and causing disease – and this approach had been very successful, with trial data in the early days of the pandemic showing these therapies, including sotrovimab, improve the chance of survival in people with no pre-existing protection against Covid-19.

Potential decrease of effectiveness

In 2022 laboratory studies indicated that sotrovimab was no longer effective in neutralising or stopping certain Omicron infections (known as sub-variants BA.2 and BA.5) from entering cells.

The World Health Organisation therefore recommended the drug no longer be used to treat ECV people with Covid-19 and called for more trial data.

However, these lab studies had important limitations, and it was becoming increasingly difficult to run trials involving sotrovimab. This was because the overall number of people in hospital with Covid had come down, and there were more treatments being used in clinical practice, making it a challenge to run trials that were ‘powered’ effectively to assess how well sotrovimab works in the body.

UCLH-Crick research

To address this problem, UCLH and the Crick through the Legacy study partnered with the CDMU team at UCLH to test whether a variety of therapies – including sotrovimab – were still effective against the new Covid sub-variants of concern: Omicron BA.2 and BA.5.

And last year, the team found that antibodies generated by sotrovimab were still able to block entry of the virus into cells and therefore offer protection.

As a result, the team called for the WHO guidelines to be changed in a paper in the Lancet in 2022, highlighting limitations in the research used by the WHO team to change their guidelines.

In parallel to the Legacy research, researchers from the London School of Hygiene and Tropical Medicine (LSHTM) and Oxford University looking at NHS data found that sotrovimab was associated with the same very low (2%) levels of hospital admissions as patients given paxlovid, and less than those patients given molnupiravir across 2022, including during times where infections with Omicron sub-variants BA.2 and BA.5 were common.

Both teams shared their data with NHS England policy makers and NICE, to show that, together, the two very different studies supported ongoing use and rolling evaluation of sotrovimab as SARS-CoV-2 continues to evolve.

The NICE guidance issued this week advises that sotrovimab can still be used for early Covid treatment for ECV adults.

Emma Wall, UCLH Infectious Diseases consultant and Senior Clinical Research Fellow for the Legacy study, said: “Living with COVID-19 means different things for different people, and it’s essential that we continue to protect the most vulnerable patients with treatment strategies that are based on robust scientific and clinical data.

“It takes a long time for new treatments to be approved for clinical use, but comparatively little time to withdraw them. With the pandemic continuing to evolve rapidly, we need to take a more strategic approach to recommendations for these clinically valuable drugs.”

David LV Bauer, Group Leader of the Crick’s RNA Virus Replication Laboratory and member of the G2P-UK National Virology Consortium, said: “Our data strongly suggest that we should be widening use of monoclonal antibodies to treat COVID-19. Different drugs have been shown to be more or less effective against new variants, when compared to previous strains. But the pace at which the virus is evolving means we shouldn’t dismiss potentially effective treatments. Continued monitoring and analysis of emerging variants is our best defence against the virus and essential to protect vulnerable people, like those undergoing dialysis or with blood cancer.”

Professor Bryan Williams, Director of Research at UCLH and Director of the NIHR UCLH Biomedical Research Centre, said: “The guidance published this week highlights the importance of the strong partnership between UCLH and the Crick in research. When Legacy was set up, we wanted to make sure treatment of Covid-19 is as effective and evidence-based as it can be, and this is what we have done. World class science at UCLH and the Crick has directly influenced national policy, and the upshot is that patients who are vulnerable will have access to a wider range of therapies.”

Image: Dr Emma Wall