In response to the decision, our Patient Advocacy Director, Zack Pemberton-Whiteley, said:
“We’re delighted the SMC has decided to make the ruxolitinib available in Scotland on the NHS for people living with PV. However, this decision creates a cross border barrier to treatment. PV patients in England and Wales cannot currently access ruxolitinib, as the appraisal by the National Institute for Health and Care Excellence (NICE), of ruxolitinib in this patient population, was terminated in January 2015. The SMC’s decision shows that this drug is effective for patients and so we will continue to work with both NICE and Novartis to push for access for PV patients across the whole of the UK.”
How does ruxolitinib work?
Ruxolitinib (brand name Jakavi) is produced by Novartis. Ruxolitinib works by targeting a group of proteins called janus kinases, specifically JAK1 and JAK2, stopping them from working.
These JAK1 and JAK2 proteins are part of a pathway known as a JAK-STAT signalling pathway. There are many pathways inside cells that exist to communicate messages from the outside world to the cell’s DNA, so that cells respond appropriately to their environment (e.g. getting white blood cells to respond to infections). The pathways start with a protein at the cell’s surface, which picks up the message. Then a series of interactions between proteins eventually leads to the transcription of, or reading of, certain genes. The cells then make proteins from these genes that allow them to respond to their current situation.
The genes that are transcribed at the end of the JAK-STAT pathway include ones that change how often cells divide and how they develop. This means if the JAK proteins are activating the pathway too often, cells don’t divide and/or develop normally, leading to the cells becoming cancerous.
In blood cancers, the JAK1 and JAK2 proteins are dysregulated. This means they activate the genes in the cell even when there is no signal from outside the blood cells. By inhibiting JAK1 and 2, ruxolitinib aims to return the activity of the two proteins in the JAK-STAT pathway to normal levels, so the cells start
What was the evidence that ruxolitinib works?
The SMC was presented with data from the RESPONSE and RESPONSE-2 clinical trials. Both trials compared the response of patients on ruxolitinib to patients who were given the best available therapy (BAT). BAT means patients were given whichever treatment the clinician decided was best for their patient, from the list of treatments that were available on the NHS at the time the trial was conducted.
To determine how effective ruxolitinib is, these trials measured whether patients had haematocrit control at 32 weeks. Your haematocrit is the percentage of red blood cells in your blood. PV patients make too many red blood cells (i.e. have a high haematocrit level), which can clog up blood vessels and potentially lead to strokes; . A patient was said to have haematocrit control if they had a haematocrit level of less than 45% by week 16 and maintained it for at least another 12 weeks, plus did not need phlebotomy (the process that thins the blood by removing some) after week 4. In the RESPONSE-2 trial, when patients were examined at week 32, 60% of those on ruxolitinib had haematocrit control, vs. only 19% of those on best available therapies. This is a significant result.
The manufacturer, Novartis, also presented evidence that their drug was cost effective. In the UK, the NHS has set a limit on the amount of money that can be spent on a drug per Quality Adjusted Life Year. A QALY is a way of measuring the extra survival time that a treatment can give a patient, whilst also account for the quality of life during those extra years. The limit that was applied to this treatment was a maximum of £30000 per QALY. The company presented economic models that suggested that the drug would not cost more than the limit, and the SMC deemed ruxolitinib to be cost effective.
Why are new treatment options important for PV patients?
One of Leukaemia Care’s role in the drug appraisal process is to inform the SMC team about how PV affects people’s lives day to day. We also provide evidence for patient preferences, such as types of treatments people prefer or where they would prefer treatment to be delivered. This evidence comes from our survey, Living with Leukaemia, as well as focus groups and conversations with individual patients. We provide this information by submitting a written statement, and by attending a meeting known as Patient and Clinician Engagement (PACE) meetings, where we engage in a discussions about the needs of patients and how the new treatments meet those needs.
PV is a chronic condition, meaning that current treatments do not cure it. For some it is easily controlled with hydroxcarbamide tablets, with mild symptoms and side effects. However, in our survey, only 7% of PV patients report a full improvement in their symptoms, and only 33% report a significant improvement. For these patients whose disease cannot be easily controlled, life can extremely uncomfortable. For example, patients describe constant itching as a particularly difficult symptom; one lady described her itchy skin as unbearable. Fatigue is also a challenge for a lot of patients. Additionally, patients who need regular phlebotomy, because they have no drugs to control the cell production, must go into hospital to have it done, preventing them from working or even going away from home for a break.
For these patients who cannot have hydroxycarbamide, yet are struggling with symptoms, the other options are limited and have significant flaws. In our survey, 84% of PV patients report that they did not have a choice of treatments. Some alternative options only partially work, or work for only a small number of patients, and some have significant side effects such as increasing the risk of secondary cancers. Best available therapy was picked as a comparison treatment in the trials because there is no agreement among clinicians which is therapy is best, as all the options are so poor and decisions can depend on whether patients stay well enough for intensive treatment.
Ruxoltinib is an effective treatment, relieving symptoms and controlling the disease. It is not without side effects of its own, but it was felt in the SMC process that, as other options are so poor, there is a significant need for this treatment.
You can find out more about this decision here: https://www.scottishmedicines.org.uk/medicines-advice/venetoclax-venclyxto-full-smc2166/ or contact our advocacy team by emailing firstname.lastname@example.org or calling our helpline 08088 010 444.