Leukaemia Care and the MPN Voice successfully campaign for patients with myelofibrosis to access new treatment

The role of NICE in England is to decide if a treatment is cost-effective for use on the NHS. They do this by comparing the treatment to existing treatments, if there are any. The process involves looking at clinical trial data and information on the cost of delivering the new drug. A committee of people at NICE then makes a recommendation based on the evidence they have.

Both Leukaemia Care and MPN Voice provided a submission which outlined the value of the treatment to patients. We were asked to provide evidence of the need for the treatment by discussing the limitation of the current treatments for MF. We were also asked what the advantages and disadvantages of fedratinib are.

We provided information from surveys of the patient’s community, such as the “Living with Leukaemia” survey conducted by Leukaemia Care, and an international survey called MPN landmarks. Both these surveys highlighted that MF patients experience poor quality of life when their disease is not well controlled (93% said this in the landmarks survey, the highest of all 3 types of MPN). Our submissions spoke of the fact there are very few other treatment options, so those who do not respond to these existing ones are in great need of new treatments. Therefore, we argued that fedratinib is a much-needed treatment for MF.

The next step of the process was to attend the committee meeting. MPN Voice invited a patient who is living with MF, who was able to describe to the NICE committee the impact of MF on their life and how a new treatment is vitally needed. Also present were two clinical experts, Professor Claire Harrison (founder of MPN Voice) and Professor Adam Mead, who were able to talk about the need for fedratinib in the patients they treat.

Myelofibrosis (MF) is a blood cancer which causes scar tissue to build up in your bone marrow. The scar tissue then stops the bone marrow from creating new blood cells. MF can happen spontaneously (called primary MF) or can happen in people who have been previously diagnosed with a different type of MPN, like ET or PV (secondary MF). Your blood cells need renewing quite frequently (exactly how often depends on the type of blood cell), so it is important your bone marrow can create new ones when needed. In people with MF, the spleen and liver can often take over the production of new blood cells when the bone marrow can’t any longer.

One of the symptoms of MF is splenomegaly, or a swollen spleen, which happens when the spleen starts filling up with the blood cells it makes. If the spleen then becomes too full, it will either destroy the blood cells or keep them in the spleen rather than releasing them into the blood. The person may then have too few blood cells, causing many of the other symptoms of MF (e.g. anaemia, fatigue etc.).

Fedratinib is a tyrosine kinase inhibitor. Tyrosine kinases are proteins that activate other proteins in cells, and they are commonly associated with cancer cells (including other types of blood cancers). Fedratinib inhibits several tyrosine kinases proteins, but one tyrosine kinases that is important to MPN cells is JAK-2. MF patients commonly have mutations in proteins that JAK-2 interacts with. These proteins (known collectively as the JAK-STAT pathway) help a cancer cell survive because when they are mutated, as in MPN patients, they allow the cell to do things such as grow uncontrollably or avoid death. Therefore, when fedratinib inhibits the JAK-2 protein, it can prevent MF cancer cells growing uncontrollably and encourage them to die (known as apoptosis).

As part of our submissions to NICE, Leukaemia Care and MPN Voice spoke to some people treated living with MF.

Patients told us it is really challenging to live with MF. It impacts on all parts of your life, such as this person who was working at the time: “My fatigue and anaemia had a lot of impact on my high intensity job as a doctor, I had to reduce hours”. Others talked about struggling to exercise: “Due to fatigue I cannot do anything physical or exercise, I also get breathless and end up coughing”. Even when on treatment, patients struggle as “side effects was worse than any symptoms of MF”. However, those on treatment found that it reduced their symptoms, including spleen size, which should allow many patients to do more daily activities.

As well as evidence from Leukaemia Care and MPN Voice on the impact of this treatment on quality of life, clinical trial data was examined by NICE to understand the treatment. The key clinical trial for fedratinib was JAKARTA-2.

The trial showed the fedratinib did reduce spleen size in those treated. However, one challenge of this appraisal of fedratinib was that the committee were not certain that a reduction in size of the spleen correlated to better survival of patients. The clinical experts assisted the committee to understand this point, but further data is likely to be collected on patient survival whilst the treatment is available on the Cancer Drugs Fund.

Additionally, this trial was single arm, meaning that everyone on the trial had fedratinib. Not having a group of people on the alternative treatments in the trial can make it very hard to compare fedratinib with other treatments, as this then requires statistically modelling of data and/or comparing data on fedratinib to data on the other treatment in a different trial, likely set up in a different way. Once you must predict things with models, rather than comparing data sets in real people within one trial, this adds uncertainty to the decision making by the committee; they can be less sure that fedratinib is more cost effective than existing treatments.