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First Baby Receives Life-Saving Gene Therapy on NHS

In what is being described as a "breakthrough moment", the NHS has provided for the first time a life-saving gene therapy treatment for the fatal disorder metachromatic leukodystrophy to a baby.

Metachromatic leukodystrophy (MLD) is genetic disease that causes severe damage to an affected child's nervous system and organs, resulting in a life expectancy of just 5 to 8 years. It is estimated that around four babies born every year in England will have the condition.

The genetic disorder prevents the development of a crucial enzyme, arylsulfatase-A, and this leads to a build-up of sulfatides that then destroy the myelin sheath of the nervous system. This results in symptoms that include peripheral neuropathy, muscle weakness, sight and hearing loss, difficulty walking, loss of speech, cognitive decline, and seizures.

How quickly the disease progresses and how long children with it live varies based on age when symptoms appear. Children with the late infantile type of MLD, which starts before 30 months and is the most common and the most rapidly progressing type, deteriorate rapidly and usually die between the ages of 5-8 years. Children with early juvenile MLD, which usually starts between 30 months and 6 years, have a life expectancy of 10-20 years after onset.

Deal Struck, Guidance Issued

Previous treatment options for MLD were limited to managing symptoms and supportive care. However in February last year, the NHS struck a deal to provide a gene therapy called atidarsagene autotemcel (Libmeldy), manufactured by the UK-based biotech company Orchard Therapeutics, to NHS patients with MLD. The therapy is a one-time treatment that involves removing the patient's stem cells, replacing the faulty gene that causes MLD with functional copies, and then re-injecting the treated cells as a single-dose intravenous infusion, thus correcting the underlying cause of MLD.

In March last year the National Institute for Health and Care Excellence (NICE) published its final guidance after its committee members had concluded that “MLD is a rare, serious, and life-limiting condition that significantly affects the lives of people with the condition, their families and carers”.

The regulator recommended the use of atidarsagene autotemcel, within its marketing authorisation, as an option for treating metachromatic leukodystrophy with mutations in the arylsulphatase A (ARSA) gene:

  • For children who have late infantile or early juvenile types, with no clinical signs or symptoms
  • For children who have the early juvenile type, with early clinical signs or symptoms, and who can still walk independently and have no cognitive decline

NICE emphasised that the recommendation prevailed only if the company provided the treatment "according to the commercial arrangement". The regulator also stated that atidarsagene autotemcel should be delivered in a 'highly specialised' service by a specialist multidisciplinary team.

NICE explained that clinical evidence suggested that atidarsagene autotemcel "improves motor and cognitive function in the short term" and could correct the enzyme deficiency caused by the disease. It added that cost-effectiveness estimates showed that atidarsagene autotemcel provides "substantial extra health and quality-of-life benefits", although pointed out that these "vary" for the different types of the disease.

On publication of the guidance, Helen Knight, programme director in the Centre for Health Technology Evaluation at NICE, highlighted that NICE recognised that MLD is a "life-limiting, relentless, disabling, and isolating condition", affecting all aspects of patients' and caregivers' lives. It also recognised that treatment options for MLD were "limited" to managing symptoms, and that there was a "significant unmet need" for disease-modifying therapies for MLD.

Breakthrough Moment

The gene therapy has a list price of £2.8 million and was the most expensive drug in the world when NHS England negotiated a significant confidential discount last year to make the treatment available to NHS patients. "It remains the most expensive drug licensed in Europe", an NHS England spokesperson said.

Professor Simon Jones, consultant in paediatric inherited metabolic disease, Manchester Centre for Genomic Medicine at Saint Mary's Hospital, and clinical director of NIHR Manchester clinical research facility at Royal Manchester Children’s Hospital, explained that MLD is a "progressive, life-limiting" condition and that prior to this metabolic disorder service being made available via the NHS, there were "no approved treatment options available".

"While there are various sub-types of the condition," he explained, "in its later stages, all forms largely result in children losing their ability to move and speak." He said that his experience permitted him to "testify to the devastating impact" the disease can have.

The treatment is available on the NHS as a specialist service and is being delivered within Royal Manchester Children’s Hospital. The Manchester centre is one of just five European sites administering the treatment, and the only site in the UK.

The first child in the UK to receive the treatment outside of a clinical trial is now 19 months old, having started treatment when she was 12 months old. She is said to be a "happy and healthy toddler showing no signs of the devastating disease she was born with".

Professor Rob Wynn, consultant paediatric haematologist at Royal Manchester Children's Hospital, and director of the hospital’s paediatric bone marrow transplant programme, said: "Through the years, colleagues and I have looked after a range of patients with rare but severe conditions, where treatment has been limited.

"It is wonderful to be involved in this breakthrough moment and deliver a gene therapy which will transform outcomes for patients with MLD," he heralded.

Vivienne Clark, chair of MLD Support Association UK, said the charity was "absolutely delighted" that the first patient with late infantile MLD had received treatment and will now be expected to lead a normal life.