Cambridge University Hospitals (CUH) is regarded as one of the most reputable medical institutions worldwide and provides specialist services to many conditions nationally and internationally, including being a Neuromuscular Centre of Excellence as awarded by MDUK. Therefore, it begs the question, why, when the FDA, MHRA and most other Neuromuscular Centres across the country are prescribing risdiplam to patients of all ages, does CUH feel able to have a different opinion to all of these experts?

Do we see a form of “Cambridge Arrogance” in that they do not like to be told how to do things? Is their ego more prominent than the depth of their expertise? Are they just naïve and do not understand neuromuscular conditions? Is it because it is not a Cancer treatment? Or is it something more sinister such as age discrimination? This is now the second time that CUH has refused to treat patients with Spinal Muscular Atrophy (SMA), a debilitating and life-limiting condition, which causes the muscles throughout the body to weaken. Last year a drug called Spinraza was approved for use by the NHS, and while providing the treatment for children, again CUH decided not to extend the same courtesy to adults.

Spinraza is somewhat of a different discussion because of the nature of its delivery. Delivered through lumbar puncture, this can often be difficult for patients with SMA due to the condition of their spine. It usually involves interventional radiology and a MDT style approach to delivery. One could almost forgive CUH for this decision because of the complexities involved, even though again, other hospitals across the country are quite happy to administer. The reason given for them not providing the treatment was that NHS England felt that they did not have enough expertise and had not published enough papers with regards to neuromuscular treatments. Still, the reality is that it was one of choice by CUH.

This now brings us onto risdiplam; an oral medication provided free of charge by Roche, which requires minimal hospital intervention other than prescribing. Let me reiterate several parts of that sentence, free, oral and minimal hospital intervention. Surely this sounds like the Holy Grail from a clinical perspective? What makes it even more exciting is that the Medicines and Healthcare products Regulatory Agency (MHRA), the government body responsible for regulating all medicines in the UK to ensure that they are effective and acceptably safe, the government agency trusted to tell us whether the coronavirus vaccine is safe or not, approved risdiplam for use in all patients that have the more severe forms of SMA and who are over the age of two months old. There was no upper age limit.

Despite these overwhelming positives, CUH has managed to ignore all of this and deny treatment to anybody over the age of 25. You may be asking why? So are we! So is NHS England, who were keen for Cambridge to prescribe as there is no availability of Spinraza to adults across the East of England, again, another failing of CUH. MHRA has also questioned why CUH has arrived at a different conclusion to its own national expert scientists, as have Roche themselves.

We provided evidence and natural history information with regards to SMA; we facilitated discussions with the MHRA and CUH as well as Roche and CUH to ensure that they could get clarification on any points they were unsure. After all, so far, they have shown little understanding of the condition, so this could only help. Not only did they have this extra assistance, but they also had access to the same data and research available that all the other hospitals across the country who are prescribing have access to. Did this help? Unfortunately, not, CUH spotted something in all of that data that the MHRA and all the other hospitals have missed? Really?

I think it is fair to say that, CUH is not quite as impressive as it likes to think it is. The process for approval for such medicines is through some form of Drugs and Therapeutics Committee meeting where several clinicians, managers and pharmacists sit around a table and make life-altering decisions. In theory, a clinical expert should be in the room to present justification for providing this treatment, the only problem is, what happens if the hospital does not have any clinical expertise? Well, the answer appears quite simple, the decision is made by people who neither have any interest or knowledge in the condition, including a Committee Chairman and haematological oncologist who knows nothing about neuromuscular disorders.

Despite us challenging the decision on numerous occasions we have been unable to convince this “world-renowned” hospital to do the right thing. They argue that there is not enough data on efficacy in adults over the age of 25. They are correct; we cannot deny this, most people with SMA do not live beyond the age of 25, and this is a brand-new treatment, so obviously there is no efficacy data. However, MHRA has confirmed that it is safe, there are no-cost implications to the hospital or local health economy, and at the absolute worst-case scenario, it would stabilise people’s condition.

The science behind the treatment is clear, there can be no doubting its effect. The only unknown is whether the treatment will improve someone’s condition based on their age. A recent survey of adults with the condition showed that 96% would feel overjoyed at the opportunity of not deteriorating further. I am sure if these people in the room, making the decisions, were in the same position as these deteriorating patients, they would be more than happy to accept stability. In fact, it was only recently that we managed to convince CUH that stability of the condition is an acceptable outcome. Yet despite this they still refuse to prescribe, once again science says one thing but the “experts” at CUH say something different.

While you can devise all manner of clinical or scientific reasons not to do something, how can this be right morally and ethically? A decision to subject those with the condition to the mental torment and anguish knowing that they could wake up tomorrow morning and lose the ability to talk, or swallow, or even breathe!
It was Hippocrates; the Greek philosopher, considered the father of modern medicine, who first developed what we know as the Hippocratic oath. Much like anything, it is open to interpretation, but a key tenant of it is ‘primum non nocere’, or ‘do no harm’ to patients. While this was probably directed towards deliberately harming patients, let us be honest, harm through omission is just as bad. For those who don’t believe in the above, of which I’m sure some of those were in the Drugs and Therapeutics Committee meeting at CUH, can also look at the GMC Good Medical Practice guidelines which include many of the principles of the original Hippocratic oath.

Let us look at a couple of specifics:

• Make the care of your patients your first concern; (as opposed to egos or politics)
• Apply knowledge and experience to practice; (assuming you have the knowledge and experience)
• Recognise and work within the limits of your competence; (don’t make decisions about things that you don’t understand)
• Respect patient’s rights to reach decisions about their treatment and care, as well as supporting them in caring for themselves to improve and maintain, yes maintain, their health! (This is a good one, patients should be able to have complete control over their health care, and clinicians need to accept that sometimes patients know more about the condition than they do)
• Treat patients and colleagues fairly and without discrimination. (We assume this includes age discrimination which appears to have been forgotten by CUH when it comes to risdiplam)

Yet despite all these arguments and “good medical practice guidelines” we still find ourselves in a position where those who do not understand making decisions for those who do.

We can write about this because we are some those people that this treatment would benefit. We know the mental anguish of dealing with a body that is slowly dying long before the brain does. We understand it both from the patient’s perspective and carers. Watching our body give up before it is ready, and this is something that many patients had come to accept. However, with many millions of pounds spent with expert scientists across the world, people with SMA have a small chance of some hope. Not of running in the next Olympics, or starring on Strictly Dancing, but of being able to breathe, function, live just a little bit longer than was initially anticipated. Is that too much to ask? Apparently to CUH it is.

We have tried to seek conversations with the CEO and/or Medical Director. Still, as yet nothing has been offered except for them to continue hiding behind the Haematology Oncologist who appears able to make decisions on what treatment is appropriate for patients with neuromuscular conditions, and, also, who knows more than the MHRA. What is worse, is that these people, supposedly at the forefront of medical science and committed to patient care, often simply ignore you. They do not want “peasants” questioning them, their decision is final. That is how it feels to a patient, an organisation whose values are Safe, Kind and Excellent, making patients feel worthless.

Over the years there have been many stories such as this, the NHS not providing care to people because it’s too expensive, or there is a lack of evidence, but in many of these examples cost tends to be the biggest stumbling block. We all know the NHS has a finite budget, therefore there must be some checks and balances put in place to ensure we, as taxpayers, get value for money. That is going to become even more important over the coming years as we recover from the pandemic. However, just to remind everybody, this treatment is FREE now.

We going to close by asking CUH to stop being so stubborn, arrogant, devout of compassion or empathy, disrespectful and, most importantly, wrong about this decision. You are not the all-knowing entity that perhaps you think you are, and with the NHS focusing on inequalities in access to health, we and others across the East of England are asking CUH to stop this age discrimination now, and if you’re not prepared to, NHS England must.

How you can help

We have already received press interest with regards to this story both locally and nationally and will be discussing this with them in due course. However, as we have seen many times before, the strength of the SMA community comes from working together and fighting as a group. We would urge you to contact the relevant people listed in this article and tell them what you think of them actively discriminating against adults with SMA, and even more importantly, leaving all adult patients across the East of England without treatment.

Alternatively, we’ve made it nice and easy for you to email CUH and tell them exactly how you feel by clicking here. By clicking the link you should get a preformatted email which you can use to contact the hospital, use the text provided, add your own, add to the text provided, it’s entirely up to you. Regardless of whether you are in Cambridge or somewhere else in the UK, even our international friends, we fight as one and must stand together against injustice towards those with SMA. At present the whole of the East of England is deliberately being denied treatment by CUH and we ask you for your help.

Evidence that CUH wants to ignore

These are just a few example that show the impact this treatment can have on older patients:

• https://youtu.be/EUCsSDjuuKM
• https://youtu.be/tl-2w_vkaWY
• https://youtu.be/WGVnF3KDpBU
• https://youtu.be/Bguayjoat6U
• https://youtu.be/LOFaGgq1SyE
• https://youtu.be/MUF4Je8WB2w
• https://youtu.be/ls5P2LSacVg

About SMA

Spinal muscular atrophy (SMA) is an autosomal recessive neurological disease characterised primarily by the degeneration of spinal motor neurons, resulting in progressive weakness of essential skeletal muscle activity such as moving, speaking, breathing and swallowing and significantly reduced life expectancy. SMA is classified into four subtypes (Type 0–4) according to age at onset and the motor milestones reached.

• SMA type 0/1 – Is usually diagnosed in very young infants before the age of six months. The most severely affected infants have reduced movements even in utero and are born with contractures and breathing difficulties. SMA, up until the recent development of treatments, was the largest genetic killer of children under the age of two years old, mostly caused by respiratory failure.
• SMA type 2 – This is usually diagnosed somewhere between six and 18 months although can present earlier. Often, patients are able to sit without support but are unable to stand or walk unaided. Patients with type 2 often suffer from respiratory difficulties including hypoventilation in sleep. Life expectancy is reduced but most individuals live into adolescence or young adulthood.
• SMA type 3 – Is usually diagnosed after the age of 18 months and patients can often walk independently. First symptoms are often difficulty in walking, running or climbing steps due to the proximal leg muscles becoming impacted. While prone to respiratory infections most type 3 patients have a normal lifespan.
• SMA type 4 – A rare form of the condition with symptoms generally only become evident beyond the age of 21 years of age.

Most (95%) SMA cases are caused by the deletion and/or mutation of the survival of motor neuron 1 (SMN1) gene, resulting in insufficient levels of functional SMN protein. A second very closely related gene, SMN2, produces low levels of functional SMN protein, primarily due to a pre-mRNA splicing error. The major transcription product of SMN2 is a shorter and non-functional SMN protein predominantly because of exon 7 skipping due to a single nucleotide transition. In patients with SMA, reduced quantities of full-length and fully functional SMN protein can be produced by SMN2; thus, higher copy numbers of SMN2 result in milder phenotypes. Targeting SMN 2 splicing is the area of therapeutic industry and, with exception of direct gene therapy replacement in infants, remains the only viable option for many people with SMA.

About Risdiplam

Risdiplam is a SMN 2 directed RNA splicing modifier. The treatment addresses the underlying cause of SMA by increasing the amount of fully formed SMN protein that the SMN 2 genes produce to mitigate the impact of the SMN 1 deletion. There are several peer review publications about the method of action of risdiplam and its efficacy described from in vivo, in vitro and human clinical studies.

Unlike the only licensed treatment for the condition, which is administered by lumbar puncture, risdiplam is an oral medication to be taken daily. In August 2020 the drug received FDA approval for all ages and types and in the US In September, MHRA introduced an Early Access to Medicine Scheme (EAMS) for all patients with SMA type 1 and 2 over the age of two months. EMA is currently reviewing the licensing for the treatment for across the EU. In parallel NICE and NHSE have started to appraise the treatment to be introduced as standard NHS protocol for the condition as soon as possible.

Media contact treatsma@treatsma.uk