A new clinical study has opened in Ireland for a rare but devastating type of bone marrow cancer. Irish patients with advanced myelofibrosis will have access to a new study of combined oral medications for their disease.

 Frank Giles, Professor of Cancer Therapeutics at NUI Galway and Trinity College Dublin, is leading the study with Eibhlin Conneally, Consultant Haematologist at St James’s Hospital, Dublin. The Irish study is being run in conjunction with centers in France, Italy, and the UK and patients may be enrolled at either Galway University Hospitals or St James’s Hospital.

 The study involves a combination of Ruxolitinib, manufactured by Novartis, along with another pill that also targets the abnormal pathways that drive myelofibrosis. This news comes within weeks of Ruxolitinib becoming the first and only product approved for this disease by the US Food and Drug Administration (FDA).

 Myelofibrosis is a life-threatening cancer of the bone marrow that results in bone marrow failure because the normal spaces in which blood cells are formed become progressively filled with fibrous tissue. In an attempt to maintain normal blood cell counts, the body then begins to make these cells in abnormal sites including the liver and spleen. In turn, these can then become enlarged and painful. Patients not alone are at risk from marrow failure, but in some patients, myelofibrosis changes into a particularly aggressive form of acute leukemia.

 According to Professor Frank Giles, who is also Director of the HRB Clinical Research Facility Galway, a joint venture between Galway University Hospitals and NUI Galway: “We are delighted to finally have our first effective therapy for patients suffering from advanced myelofibrosis. This is a significant positive advance in treatment for these patients. We are very pleased to be able to offer this study to patients here in Ireland, especially as Ruxolitinib has just been approved in the US. We hope that approval in Europe will happen soon but in the interim we have an opportunity to build on this, our first broadly effective therapy for a very debilitating illness, and hopefully offer even better therapy with a combination of medications in the near future.”

Ruxolitinib is specifically directed at an abnormally active enzyme or kinase that has been recently defined as a key driver of myelofibrosis. “This kinase, called Jak-2, has emerged as a key target for therapy in myelofibrosis”, said Dr Conneally. “It is a central driver of the disease and inhibiting its function with Ruxolitinib directly improves many patients’ symptoms and reduces their spleen swelling. It is the latest big success in our move away from non-specific cell-killing drugs towards safer, more targeted drugs that are really directed at the fundamental drivers of cancer.”

Professor Giles, who has been involved with the development of both of the drugs  being combined in the study, said: “Success in anti-cancer therapies are increasingly driven by a continuous process which involves pre-clinical scientists unlocking the puzzles of what actually makes a cancer cell behave differently from its normal counterpart. Once you have mapped the cancer process, you can define a cancer cell’s key vulnerabilities which leads you to relatively selective targets. Next steps are the creation and testing of drugs or other approaches directed at these targets that will  alter cancer cell behaviour in terms of either killing it or forcing it to behave more like a normal cell. Once these approaches are available to our patients, we return to pre-clinical science to refine and improve anti-cancer therapy, for example, by combining agents with different targets as we are doing on this study.”

He concluded: This ‘bench-to-bedside-to-bench’ process has allowed not only the development of Ruxolitinib but allowed us to develop logical ‘next-wave’ potential therapies for patients with myelofibrosis. Collaborations over the last decade between scientists around the world have led to Ruxolitinib being available. Collaborations within Ireland and with our European colleagues have allowed us to offer this study in such a timely manner to Irish patients – a very encouraging template for future success.”

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