Campaign for Phenylketonuria (PKU) sufferers

Christina Rees MP

I didn’t know anything about Phenylketonuria (PKU) until I was contacted by some of my constituents who told me that PKU is a rare metabolic disorder which prevents people from metabolising phenylalanine (phe) which is an amino acid found in protein foods. The standard treatment is a low phe diet, removing almost all natural protein, which is replaced by prescribed medical dietary proteins to ensure adequate nutrition. The PKU dietary regime is complex and very restrictive. One of my constituents suffers with Classic PKU, a more severe form of the disorder, in which the liver can only cope with absolute minimum levels of phe.

A young constituent told me her heartbreaking story of living with PKU. She was diagnosed at birth, by the heel prick test, and has been on the PKU diet ever since. Imagine how difficult the simple everyday things that we take for granted must have been for her — having lunch with her schoolmates when she couldn’t eat anything on the menu, going out for a meal with her parents, visiting the local cafe with her friends, going shopping and seeing all the foodstuff that she couldn’t eat. She stopped trying to explain to her friends, stayed at home, and asked herself “why me”? What a lonely life she had. At the age of 12 she rebelled and started eating normal food, but went back on the diet just before she was due for a scheduled regular medical check-up, making sure that her phe levels were low. However, the effect of abusing the PKU dietary regime for long periods produced these symptoms: continually tired; light-headed; dazed; confused; poor concentration; memory loss; emotionality; anxiety and depression, and was referred to a dietitian, metabolic specialist and a psychiatrist. She had a low immune system, colds, flu, despite having a flu jab every year. Off diet she had low iron, B12 and folic acid levels, plus a risk of Osteoporosis. She hid away because she “hated her life”. I wanted to help this brave young constituent, and the other constituents who had come forward to tell me their experience of living with PKU.

I became the vice-chair of the All Party Parliamentary Group (APPG) for PKU when it was formed by my dear friend Liz Twist MP for Bladen in 2018, and I met the amazing volunteers who run the National Society for PKU, which was set up in 1973 by Brian and Sylvia Smith. There are no full-time staff, no premises — it is a charity run by people with personal experience of PKU, and is a founder member of the European Society of PKU and Allied Disorders.

We have held many events in Parliament to raise awareness of this little-known metabolic disorder. Westminster Hall debates in June 2018 on PKU and in March 2021 on the U.K. Rare Diseases Framework.

I took part in the PKU challenge, where MPs followed the restrictive diet for 24 hours, and even though I’m a lifelong Vegan, I struggled, because I love soya milk, soya yogurt, bread and crisps, which are not permitted on the restrictive PKU diet. One of my constituent’s PKU diet permits 3 grams of protein a day, which would be 3 packets of ready salted crisps, and no other protein.

I learned that managing PKU is extremely complicated. Every meal, snack, or drink, has to be carefully planned in advance, and takes a long time to prepare. It is estimated that patients with PKU and their families spend an average 19 hours per week managing their diet.

The disability benefit Personal Independence Payment (PIP) is assessed based on how much help a person needs with ordinary daily living activities (like cooking or washing) and their mobility. One of the key ‘daily living activities’ is managing therapy or monitoring a health condition.

But the DWP has not routinely accepted that the PKU diet is a “therapy”, which means that people with PKU are often denied the ‘daily living activities’ component of PIP, even though, as already mentioned, many patients need several hours of help from relatives each week to manage their diet.

A 21 year old man took legal action against the DWP, when his application for PIP was refused. His case was originally heard by the First Tier Tribunal in 2018 which agreed with the DWP in finding that his PKU dietary regimen was not a “therapy”and therefore he did not meet enough of the criteria in the PIP Regulations to qualify for PIP payments. The Claimant appealed to the Upper Tribunal, which said the First Tier Tribunal had not given adequate reasons for their decisions and should look at the case again.

The First Tier Tribunal changed its original decision and found that the PKU diet was a “therapy” under the PIP criteria, that the 21 year old needed help with his “therapy” which took more than 14 hours per week and so met the criteria to qualify for PIP payments.

This is a significant development for PKU sufferers but it remains to be seen if this result will change decisions for PKU applications for PIP in the future, but claimants should expect to be awarded £87.65 per week for being on a PKU diet.

I attended the NSPKU event in Cardiff where I listened to people who have suffered with PKU, and with incredible determination, have done their very best to lead as normal a life as possible under very challenging circumstances. I joined in the breakout groups and learned more about the foods that are permitted, in what quantity, and those foods that are definitely not permitted. The sugar tax on drinks has had an enormous effect on PKU sufferers, because a sugary drink is the “go-to” for calories. But some companies, to avoid paying sugar tax, have replaced the sugar in their well-known drinks with aspartame, which is toxic for PKU sufferers.

The NSPKU has been running a campaign for many years, for sapropterin (Kuvan), a pharmaceutical treatment for PKU which makes it much easier to manage PKU by lifting the restrictions of dietary treatment, and allowing a normal diet, to be available for all PKU sufferers. Despite Kuvan being authorised by the European Medicines Agency (EMA) in 2008 for it to be available for all people with PKU in the UK, it has not been prescribed.

The National Institute for Health and Care Excellence (NICE) finally published its draft guidance for Kuvan on 25th February 2021, with the following recommendations:

Kuvan should only be available for under 18s, because it is cost effective for children, but not cost effective for over 18s.

The dosage should be 10mg per kg of the weight of the under 18, but clinicians may prescribe within the marketing authorisation of 5–20 mg per kg. In January 2021 Kuvan cost £597.22 per 30 tablets, each tablet contains 100 mg. The NSPKU criticised this recommendation because it is based on a crude economic model, with an arbitrary cut off period at a child’s 18th birthday.

Whilst I welcomed this recommendation for children, it would produce a cliff edge at 18, where PKU sufferers on Kuvan would go from a relaxed normal diet to a severely restrictive diet overnight, and would not have the coping skills required to suddenly go onto a very strict low protein diet. Becoming an adult is stressful enough without coming off Kuvan.

NICE asserted that the brain does not continue to develop in adulthood, but there is medical evidence that the brain does continue to evolve, for example patients who have suffered strokes, produce new nerve cells.

NICE did not consider that many adults with high phe levels suffer brain fog, poor memory and depression. Or that PKU sufferers with learning difficulties need help with their diet, thus reducing their independence.

NICE recommended that Kuvan should not be taken during the pre-pregnancy and pregnancy period and did consider Maternal PKU Syndrome. The harm of high levels of phe in early pregnancy was not included in its cost analysis.

NICE has assessed cost effectiveness of Biomarin’s Kuvan on its pricing offer, but cheaper brands will soon be available when Kuvan goes off patent and generic unbranded versions of Kuvan are available.

The recommendation to supply Kuvan for children on a cost analysis basis is very short term thinking and hasn’t taken into account the long term expense to the NHS for prescribed medical dietary proteins for all PKU sufferers for their entire lives.

The public consultation on NICE’s recommendations contained in its 25th February guidance lasted until the 18th March and many clinicians, medical organisations, people with PKU, their families and their advocates submitted evidence.

NICE met on 7th April to consider the consultation submissions and published its final recommendations on 20th August 2021. NICE has reassessed Kuvan and made the following amendments to its guidance: Kuvan will now be available for patients until they reach their 22nd birthday; patients older than 22 will not be able to start taking Kuvan due to the higher average costs of treating adults; patients who are pregnant can take Kuvan from the date of their positive pregnancy test until they give birth; they are aware that cheaper generic versions of Kuvan will be available soon and “hoped these would be priced to allow access to this drug for all adults with PKU”.

NSPKU are very concerned that NICE’s determination to follow “aged based” guidance discriminates against the many adults who struggle with PKU, and that its economic model yet again produces anomalous results for patients. None of the consultation responses from medics recommended a patient’s 22nd birthday as a cut off point. NICE accepts that some adults cannot manage to control their phe levels by dietary treatment, but has left these people without realistic treatment options, and has failed to take into account the social care costs for people who can’t look after themselves because of PKU related problems. All consultation comments from doctor’s organisations recommended access to Kuvan for women planning a pregnancy, rather than from when a women discovers she is pregnant. And the British Inherited Metabolic Disease Group, which represent doctors and healthcare professionals specialising in metabolic diseases, went further in suggesting that NICE should change its recommendation to allow all women of child bearing age — 14–45 years — to be assessed for Sapropterin responsiveness and those who are responsive should be offered Sapropterin as a first-line option when they are planning a pregnancy (pre-conception period) and for the duration of pregnancy. With NICE’s minimal recommendation, there will be continuing delay whilst response testing and prescribing is put in place. Bio Marin currently has the patent exclusivity for Sapropterin, but once this ends, cheaper generics will be licensed by the Medicines and Healthcare products Regulatory Agency (MHRA). NSPKU is urging NICE to immediately assess generic Sapropterins and to reconsider its decision not to prescribe for all adults with PKU.

In January 2021, the U.K. Government published a new U.K. Rare Diseases Framework, which demonstrates commitment to improve the lives of people with rare conditions over the next five years. There are four priorities outlined in the Framework: faster diagnosis; increased awareness of rare diseases; better coordination of care; and improving access to specialist care, treatments and drugs. The four Home Nations must produce action plans to deliver these priorities. In Wales, Genetic Alliance U.K. represents the patient voice on the group responsible for developing and implementing a Welsh action plan, which is scheduled to be published by April 2022. The engagement of the rare disease community is vital to shaping the future of this new policy to ensure that it impacts those affected by rare and genetic conditions in Wales.

My constituents who suffer with PKU tell me that they want to be put on Kuvan, they appreciate that it only works for around 30% of the PKU population, but they want the opportunity to live a normal life.

It will be NSPKU’s fiftieth anniversary on 28th June 2023. Wouldn’t it be wonderful if we could celebrate with the announcement that NICE has recommended that Kuvan be made available for all people suffering with PKU.

Christina Rees is the Labour MP for Neath

The Fabian Society in Wales