New trial to repurpose cancer drug for COVID-19 patients

A new trial repurposing a blood cancer drug for patients with COVID-19 is being launched. The trial will study the use of ruxolitinib (Novartis Pharmaceuticals), a JAK inhibitor, to investigate its effect on reducing complications in deteriorating COVID-19 patients, the need for intensive care and death rate. Researchers from King’s College London and Guy’s and St Thomas’ NHS Foundation Trust will begin the trial next week. The research has been funded by LifeArc and the Masterstroke Polycythaemia Fund.

Patients with severe COVID-19 can experience hyperinflammation. This means that the levels of pro-inflammatory cytokines are elevated and can induce harmful inflammation. This reaction can send the body into shock and ultimately damages multiple organs, such as the heart, lungs and vascular system. This response can be seen in severe autoimmune and inflammatory diseases.

JAK inhibitors, such as ruxolitinib, block the signals required to produce more pro-inflammatory cytokines and therefore reduce inflammatory activity within the patient. It is currently approved for use in certain myeloproliferative neoplasms (MPN), rare forms of blood cancer, but researchers hypothesise it can prevent hyperinflammation in COVID-19 patients.

Initially 19 patients will participate in the trial, which is based at Guy’s and St Thomas’. If the first phase is successful, the trial will proceed to the next stage and a total of 59 patients will be enrolled.

Dr Shahram Kordasti, Senior Lecturer at King’s College London and the scientific lead, said: “This is a very exciting project and thanks to support from LifeArc we aim to identify immune signature(s) which predict response to JAK inhibitors in patients with severe form of COVID-19.

“This is extremely important for identifying the right time for intervention. We will use cutting edge methods to identify the best time and most suitable patients for therapy and to evaluate the immune response following therapy.”

Dr Sophie Papa, Clinical Reader at King’s College London and study co-investigator, said: “Repurposing of drugs to temper the immune dysregulation associated with severe COVID-19 morbidity and mortality is a widely shared ambition. Understanding the impact of treatment on the human immune system in the context of COVID-19 through quality translational science is the goal of this project led by Dr Kordasti and Dr McLornan. This is rapid, robust science to guide healthcare decisions at a time when clinicians need confidence.”

The team will also be collaborating with the investigators of a similar on-going study at the Princess Margaret Hospital, Canada, and receive serial samples from their trial for immune monitoring which will increase the power of this study. Researchers will also collaborate with Dr Jonathan Irish from Vanderbilt University, US, who will work closely on the data analysis of the project.

Chief investigator of the trial Dr Donal McLornan, from Guy’s and St Thomas’, said: “If effective, this drug could reduce the number of COVID-19 infected patients needing ventilation and requiring critical care unit support. This trial is a result of medics, scientists, trial specialists and nurses working closely together to provide novel therapeutic approaches for patients unfortunately deteriorating due to the COVID-19 virus.” A clinical team from Guy’s and St Thomas’ including Prof Claire Harrison, Dr Andrew Retter, Dr David Wood and Dr Helen Winslow will also be working on this project.

Melanie Lee, CEO of LifeArc said: “This study is being supported by a grant from the medical research charity LifeArc, as part of its activities to address the need for new therapies for COVID-19. LifeArc has made £10m available to repurpose existing medicines or those in the late stage of development as this approach offers one of the fastest routes to develop new treatments that could tackle the virus and its impact.”

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