Scottish patients now have access to the only licensed oral treatment option for the rare and life-threatening blood cancer, myelofibrosis

Patients in Scotland with a rare and life-threatening blood cancer now have access to Jakavi® (ruxolitinib), the only licensed oral treatment for enlarged spleen or the symptoms related to primary myelofibrosis (MF), post-polycythaemia vera MF or post-essential thrombocythaemia MF.^{1, 2}

MF is a rare cancer of the bone marrow, in which bone marrow is replaced by scar tissue. The abnormal marrow can no longer produce enough normal blood cells and as a result the spleen becomes significantly enlarged.³ Treatment and care is centred around reducing the size of the spleen and relieving the severe and debilitating symptoms of the disease which include fever, unexplained tiredness, weight loss, itching, shortness of breath and abdominal pain.³ These symptoms have considerable impact on daily living and one in five myelofibrosis patients are reported as medically disabled.⁴ The deterioration in quality of life and diminished ability to perform daily functions is comparable to that seen in metastatic cancer.^{4, 5, 6}

MF is a rare cancer, affecting less than 2 in 100,000 people,⁷ and before the availability of ruxolitinib, treatments for MF were supportive and only targeted certain symptoms with limited effect. Ruxolitinib is recommended by the recently updated British Committee for Standards in Haematology (BCSH) guidelines as a first-line therapy for enlarged spleen or MF-related symptoms.⁸

"It's great news that the voices of clinicians and patients have been heard and agreement has been reached to provide access to ruxolitinib for patients in Scotland", said Dr Zor Maung, Consultant Haematologist, Western General Hospital, Edinburgh. "The detrimental impact the debilitating symptoms of MF have on a patient's quality of life is severely underestimated and up until now, treatment options have been limited and not proven or licensed in MF. For the first time we have a treatment that can tackle these life-altering symptoms, improve quality of life and may even increase survival for people living with this devastating cancer."

A comprehensive package of clinical and cost effectiveness evidence, highlighting the efficacy and safety profile of ruxolitinib was submitted to the SMC, including data from the COMFORT (COntrolled MyeloFibrosis Study with ORal JAK Inhibitor Therapy) clinical trial programme. These trials demonstrated significant improvements in spleen size reduction, quality of life and associated symptom reduction, including appetite loss, fatigue, shortness of breath, insomnia and pain.⁹ In addition to improvements in symptoms, ruxolitinib has also demonstrated a positive impact on survival. Ruxolitinib increased survival probability and reduced risk of death by 42% when compared to conventional therapies at 3.5 years.¹⁰

Ruxolitinib is currently available to patients in England through the Cancer Drugs Fund, as it was not recommended by the National Institute for Health and Care Excellence (NICE) in 2013. However NICE is due to re-evaluate its guidance during 2015 and given that longer term data are now available, which includes survival data, Novartis is hopeful that NICE will consider ruxolitinib favourably in line with today's SMC recommendation.

"This is fantastic news for patients in Scotland and recognises the value of this ground breaking treatment in a rare cancer that has been neglected up until now," said Margaret Dean, General Manager, Novartis Oncology UK and Ireland. "The new SMC process provides the opportunity for greater engagement with the patient community and this is a positive step forward for the assessment of new cancer medicines. We hope that NICE will reach a similar decision to ensure sustainable, long-term access to ruxolitinib for patients across the UK."

About myelofibrosis

Myelofibrosis (MF) is a rare and chronic blood cancer that affects the way blood cells are produced in the body. Patients with MF build up scar and fibrous tissue in their bone marrow, affecting its ability to produce new blood cells. As the number of new blood cells decline, production of blood cells in areas outside the bone marrow including the spleen. This results in them becoming enlarged and damaged, causing some of the symptoms associated with MF, such as abdominal discomfort, unexplained tiredness and weight loss.³

The impact of myelofibrosis in terms of deterioration in quality of life and diminished ability to perform daily functions is comparable to that observed in metastatic cancer and acute myeloid leukaemia.^{4, 5, 6} An international survey among patients reported that up to 18% of MF patients are medically disabled.⁵

The causes of myelofibrosis are not fully understood, however it can develop in a number of ways. Primary MF is where the condition occurs in patients with no history of bone marrow problems. It can also occur as a result of previous diseases in the bone marrow, such as post essential thrombocythaemia (PET) or post polycythaemia vera (PPV).¹¹

MF is considered to be a rare disease.¹¹ Estimates suggest that MF affects less than 2 in 100,000 people.⁷ Although anybody is at risk of developing the condition, MF is more common in people over the age of 60, with the average age of diagnosis being 60-70.³ From diagnosis, the median survival for people with myelofibrosis is less than 6 years.¹²

About Jakavi® (ruxolitinib)

Jakavi® is an inhibitor of enzymes called JAK1 and JAK2 tyrosine kinases,² which regulate blood cell production and are known to be overactive in myelofibrosis patients.² It is indicated for the treatment of disease-related splenomegaly (enlarged spleen) or symptoms in adult patients with primary MF, PPV-MF or PET-MF.²

The effectiveness of ruxolitinib has been demonstrated in two pivotal phase III trials, COMFORT-I and COMFORT-II.

• COMFORT-I demonstrated effectiveness of ruxolitinib in reducing spleen volume against placebo. At 3 years, 59% of patients originally randomised to ruxolitinib had achieved ≥35% reduction in spleen volume.⁹
• COMFORT-II demonstrated efficacy of ruxolitinib versus conventional therapy. At 3.5 years ruxolitinib was shown to reduce spleen size by ≥35% in 52.1% of patients, which correlated with a 42% reduction in risk of death and increased survival probability (0.71 vs 0.54) compared to conventional therapy.¹⁰

Improvement of disease-related symptoms was found in patients on ruxolitinib in both COMFORT studies, compared to placebo and conventional therapy. Ruxolitinib was effective regardless of JAK mutational status, disease subtype, or any prior treatment.^{9, 10} Significant improvements were demonstrated in health related quality of life and myelofibrosis-associated symptoms including appetite loss, shortness of breath, fatigue, insomnia and pain.⁹

The most frequently reported haematologic (blood related) adverse reactions with ruxolitinib were anaemia (low levels of red blood cells - 82.4%), thrombocytopenia (reduction in the number of platelets - 69.8%) and neutropenia (low levels of white blood cells -15.6%). Haematologic reactions were generally dose-related and manageable through dose reductions and/or transfusions, and such reactions rarely led to treatment discontinuation. The three most frequent non-haematologic adverse reactions were bruising (21.3%), dizziness (15%) and headache (13.9%).²

Ruxolitinib is available worldwide and was approved by the European Medicines Agency (EMA) in August 2012 and by the U.S. Food and Drug Administration (FDA) in November 2011. For more information, please see the summary of product characteristics for ruxolitinib at www.medicines.org.uk/emc.