Leukaemia Care and the UK Mastocytosis Support Group successfully campaign for patients with very rare condition 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.

However, this process is not well set up for rare diseases. The rarer an illness, the harder it becomes to generate enough clinical trial data and also to get clinical trial data that is high quality. Therefore, rare illnesses, like AdvSM, may be more likely to rejected because the committee are not sure the treatment is cost-effective from the evidence they do get. Both Leukaemia Care and The UK Mastocytosis Support Group raised this issue with NICE from the very beginning of the process, arguing that midostaurin should be looked at in a special process that can take into account the data collection issues (and other issues) that rare illnesses create. However, this call was rejected.

Later in the process, when raised by the health economists that there was not enough data to be sure of how cost-effective the treatment is, both Leukaemia Care and The UK Mastocytosis Support Group continued to raise that this had been known since before the process began. We again pointed out that it is extremely hard to get enough data from rare illnesses. We also pointed out AdvSM patients do not have any other options for treatment in the UK at present, except for trying treatments that were not designed for AdvSM and are not very effective, and that Midostaurin has become the standard of care throughout the world since it was approved by regulators in 2017 because it is the most effective drug for many AdvSM patients.

Another challenge of this campaign was that midostaurin is already approved for acute myeloid leukaemia in England and a price had already been agreed by Novartis in that appraisal. A cheaper price for midostaurin when used in these rare patients would mean midostaurin was easier to approve, but NHS England does not routinely allow 2 different prices for treatments if they are used for different illness. This added to the delays. Leukaemia Care and The UK Mastocytosis Support Group expressed concern about these issues in a joint letter to Matt Hancock MP, then Secretary of State for Health and Social Care, and Jess Hobart also spoke at the All-Party Parliamentary Group on Rare Diseases to raise this issue with NICE and NHS England administrators. We also wrote to Novartis to ensure they continued to work to achieve a solution.

Jess Hobart, Chair of Trustees at UK Mastocytosis Support Group, said: “This will be welcome news for patients with AdvSM in England. Our patients desperately needed this treatment; we are aware of some who have sadly passed away due to having no other treatment options in the interim time, as there was no patient access scheme in place whilst the process was resolved. There are further treatments in the pipeline for AdvSM and we would be pleased to hear how all parties intend to prevent this situation from occurring again”.

Zack Pemberton-Whiteley, CEO of Leukaemia Care, said: “We are pleased to see this finally be approved by NICE. There were many challenges to this appraisal, but it should not have taken 4 years to reach this point. We would like to see NICE learn from this appraisal when they are considered changes to their methods and processes in the next few months to avoid those with rare disease avoiding such a long wait ever again”.

Andrew Dugdale, a patient who has spent 4 years on a compassionate use program for midostaurin prior to approval said: “I’m pleased to see common sense prevail over red tape here. This campaign was too long and all parties could have done more to make this available sooner. It’s fantastic to see this treatment, which has impacted by life so greatly, will now be available to others in my situation too”.

Advanced systemic mastocytosis (AdvSM) is a collective term for 3 illnesses, each more severe than the next; aggressive systemic mastocytosis, advanced systemic mastocytosis with associated haematologic malignancy (AdvSM-AHN) and mast cell leukaemia. All 3 are illness of the bone marrow and immune cells called mast cells.  You may be familiar with mast cells, as they are the cell in the body that releases histamine. Histamine is well known as the substance that causes hayfever which is remedied by taking antihistamines, but mast cells can produce and release up to 200 other chemical mediators as well.

People affected by AdvSM of any type are susceptible to severe allergic reactions due to mast cells that react to everyday things. Affected patients have to cope with reactions to many stimuli that it can be difficult or impossible to avoid, such as extreme heat or cold, anaesthetics, other general medications, or chemical and perfumes in the environment. Not only do patients have to spend enormous amounts of time and energy avoiding triggers or exhausted from mast cell activation reactions, but they are also at risk of life-threatening anaphylaxis reactions.   In addition, because the mast cells can accumulate in the bone marrow and in other body organs, those organs can fail, shortening life expectancy significantly.  Therefore, these patients were in extreme need of access to an effective therapy as quickly as possible.

As part of our submission to NICE, Leukaemia Care and The UK Mastocytosis Support Group presented the results of a survey of patients who had taken midostaurin, and also spoke to some people caring for patients with AdvSM.

Patients told us it is really challenging to live with AdvSM. They live with a wide range of symptoms, including gastro-intestinal problems, itching and severe fatigue. These can affect their day-to-day lives hugely; one patient even describe it as: “ASM has made life a living nightmare”. We were only able to speak to patients with the least severe forms of AdvSM, yet their experience of living with AdvSM was still severe. There is a clear need for these patients to have an effective treatment.

Patients told us that midostaurin hugely improved their symptoms and helped them to live more easily day to day. One person said: “This drug made my condition so much better. My spleen has reduced in size (almost back to a normal size), my skin had cleared up, my blood levels were going towards normal levels”. A carer also highlighted the impact: “The treatment has improved their daily life. My family member now has around 8 hours a day of reasonably normal life, we are able to go on holiday and out to events which we would not have been able to do otherwise”.

Most importantly, this treatment has the potential to save lives, as these patients are at risk of a life-threatening anaphylaxis response to some triggers. One patient summarised what the extra time meant to them in this comment: “I asked my doctor if I didn’t take this medicine, how long do I have. They told me about a year. So yes, I think this medicine has been good for me, so I can see my son graduate.”

Midostaurin is a protein kinase inhibitor. Protein kinases are enzymes in cells. Normally the protein kinases relay signals from outside the cell to as series of other proteins, ultimately causing the cells to do something.   Midostaurin has three helpful effects in AdvSM:  it induces apoptosis (cell death) in mast cells, it inhibits signals carried by KIT (which is mutated in AdvSM and tells mast cells to divide when they normally wouldn’t), and it also inhibits the release of histamine.  This means that it targets the life-shortening proliferation of mast cells and also decreases the risk of serious reactions caused by mast cells releasing histamine in response to everyday things.

Because it targets specific proteins involved in causing a disease, this type of treatment is called a targeted therapy.

As previously mentioned, the rarity of AdvSM makes it hard to collect enough data for decision making. However, the 2 small studies which were conducted showed that patients do live longer with midostaurin. In one study, half the patients survived to 20.6 months or longer and in the other study, half the patients lived to 40 months or more.

However, both these trials only including patients on midostaurin, the trial didn’t compare midostaurin to something else. This meant that NICE had to estimate how effective other treatments are by looking at data available from other sources, such as databases of patient data. One study of a database of European patients was able to show that other treatments are likely to be less effective than midostaurin.