NICE recommends life-changing gene therapy for children with ultra-rare genetic disorder

The first and currently only gene therapy for children with an ultra-rare genetic disorder has been recommended by NICE in final draft guidance

It is estimated there are around 10 children with the condition, called aromatic L-amino acid decarboxylase (AADC) deficiency, in the UK, of who a small number may be eligible for treatment with eladocagene exuparvovec.

Caused by a genetic mutation, AADC leads to a wide range of severe symptoms mainly affecting the central nervous system, the body’s control system that regulates bodily functions (such as heart rate), the gastrointestinal system and the endocrine system which makes and controls hormones for mood, development, and growth.

In young children normal motor development such as head control and sitting and walking is particularly affected.

About 80% of people with AADC deficiency have a severe form of the condition. They achieve no or very limited developmental milestones and are fully dependent on carers. In very severe cases people may be bedridden with little or no motor function.

Because of how rare AADC deficiency is there is not much evidence about how long people who have it live. But clinical opinion suggests that most people die before they reach their 10^th birthday, usually because of cardiac events, multiple organ failure, pneumonia or asphyxia.

Until now there have been no treatments specifically for AADC deficiency. Management is tailored to the specific symptomatic needs of the child. It involves support from specialists including paediatric neurologists, gastrointestinal specialists, respiratory specialists, endocrinologists, orthopaedic surgeons, speech therapists, and physical and occupational therapists.

A single dose gene therapy designed to correct the underlying genetic defect, eladocagene exuparvovec (also called Upstaza and made by PTC Therapeutics), is infused directly into the brain through a minimally invasive procedure – the first gene therapy to be administered in this way. The clinical evidence shows that it improves motor development and that these improvements could be long-lasting.

NICE’s final draft guidance recommends eladocagene exuparvovec in people 18 months and over with the severe form of AADC deficiency.

Helen Knight, director of health technology assessment at NICE, said: “The committee heard from patient experts about how the lives of children with AADC deficiency are severely impacted and shortened. They also heard about the substantial effect it has on the quality of life of the person with the condition and their family and carers.

“Eladocagene exuparvovec offers transformative benefits to people with AADC deficiency, and their family and carers. The committee agreed that the clinical trials showed the potential for substantial benefits that were sometimes clearly life changing.

“Today’s decision comes after a confidential commercial deal between NHS England and the company. This recognises the uncertainty in the evidence of eladocagene exuparvovec’s long-term effectiveness and has enabled the committee to recommend it as good value for the NHS and taxpayers.”

NHS England’s National Director for Specialised Commissioning and interim Commercial Medicines Director, John Stewart said: “The NHS is continually adopting cutting-edge treatments that push the boundaries of medical science and this latest gene therapy demonstrates this once again, providing a first treatment option for children with an incredibly rare condition.

“It is testament to the abilities of NHS specialised services, staffed by incredibly talented multidisciplinary teams, that they are able to deliver novel therapies like this one and that’s why commercial colleagues work so hard to secure NHS access to innovative treatments at a price that is fair to taxpayers.”

NICE expects to publish its final guidance on eladocagene exuparvovec in April.

Source – The National Institute for Health and Care Excellence