King’s College London and Guy’s and St Thomas’ researchers to study the use of blood cancer drug in reducing complications caused by SARS-CoV-2

Research title

Ruxolitinib therapy to Avoid Ventilation and improve outcome for deteriorating COVID-19 patiENts (RAVEN)

Research organisation

King’s College London and Guy’s and St Thomas’

Researchers

Principal Investigator

Co-principal Investigators

  • Prof Claire Harrison, Guy’s and St Thomas’
  • Dr Donal McLornan, Guy’s and St Thomas’
  • Dr Sophia Papa, King’s College London

The team will collaborate on the biomarker analysis with Dr Steven Chan’s team at the University of Toronto, University Health Network who are also conducting a trial with ruxolitinib.

Potential of repurposed therapeutic for COVID-19 pandemic

In late stage COVID-19, hyperinflammation is seen. Studies have shown that in these severe cases of COVID-19, the levels of pro-inflammatory cytokines and biomarkers including interleukin 6 (IL-6) are highly elevated. In fact, similar pro-inflammatory cytokines are frequently overexpressed in autoimmune and inflammatory diseases. A pathway called JAK-STAT is responsible for controlling the level of these pro-inflammatory cytokines produced in the body. JAK inhibitors block the signals to produce more pro-inflammatory cytokines and therefore reduce the host’s inflammatory activity. JAK inhibitors have been shown to be effective in a range of inflammatory diseases such as rheumatoid arthritis.

Ruxolitinib is a JAK inhibitor which is currently approved for myelofibrosis, a rare form of blood cancer. It is hypothesised that ruxolitinib will reduce JAK activity and ultimately prevent hyperinflammation in COVID-19 patients. Due to this promising link, there are a number of additional trials registered to test ruxolitinib and other JAK inhibitors for COVID-19.

Guy’s and St Thomas’ and King’s College London secured funding from LifeArc to complete a pilot study repurposing ruxolitinib in deteriorating patients with COVID-19 disease. Researchers believe ruxolitinib may improve disease-associated hyperinflammation and prevent the need for mechanical ventilation. Data from Guy’s and St Thomas’ suggests that the current standard of care means that 30% of hospitalised patients will progress to this severe stage.

Initially 19 patients will be treated in the trial. If six or more deteriorate and need mechanical ventilation within one month, the trial will be terminated. If the trial proceeds to stage 2, a total of 59 patients will be studied. This trial will be based at Guy’s and St Thomas’. Staff there have extensive expertise in using ruxolitinib within the haematology department.

Ruxolitinib will be supplied free of charge by Novartis UK.