NICE has recommended ataluren (Translarna, PTC Therapeutics) for treating children aged 5 and over with Duchenne muscular dystrophy (DMD) caused by a nonsense mutation.
The drug has been called a ‘step change’ in the management of the disease which causes progressive muscle wasting and is usually fatal by age 30.
Children with the disease typically become wheelchair dependent by age 12 and the committee agreed that ataluren had the potential to delay the loss of ability to walk, one of the most important factors for patients and their families.
The committee heard:
- In a clinical trial, none of the children in the most sensitive group taking the drug lost the ability to walk over the 48 weeks of the trial compared with 8% on the placebo (0 out of 47 compared with 4 of 52).
- The research predicted ataluren may delay loss of walking for up to 7 years.
- Patient experts said they had seen meaningful stabilisation or improvements in their child’s mobility such as being able to get into and out of bed independently and go to school.
- Patient experts said once a child loses the ability to walk, greater deterioration follows meaning they need help with toileting and eating. If the time to loss of walking could be delayed, their children would have the opportunity to have a normal adolescence.
Ataluren is licensed for children with DMD caused by a nonsense mutation aged 5 and over who are able to walk. Its list price is approximately £220,000 per year.
Ataluren has been considered as part of NICE’s Highly Specialised Technologies programme that looks at treatments for very rare diseases that are commissioned nationally by NHS England.
The committee recommended ataluren be made available under certain circumstances, which will need to be set out in a managed access agreement between the company and NHS England:
- Within its license – for children with DMD caused by a nonsense mutation aged five years and over who are still able to walk.
- Under a confidential financial agreement between NHS England and the company. The company will need to agree a cost which is acceptable to NHS England for this guidance to be put in place.
- For five years in a ‘managed access agreement’ allowing the company to collect further data on its efficacy. The guidance will be reviewed at the end of that period.
Sir Andrew Dillon, chief executive of NICE, said: “Duchenne muscular dystrophy caused by a nonsense mutation is a cruel disease that currently has few treatment options. Ataluren is a medicine that for the first time is aimed at the root cause of the disease and has the potential to offer benefits to people with the condition and their families.
“Because of its very high cost, it is important that details of the financial and other arrangements to enable this new medicine to be offered to patients on the NHS are discussed and agreed between the company and NHS England, and set out in a managed access agreement.
“NICE acknowledges that ataluren represents a significant cost to the NHS at a time of increased pressure on funding and has considered this carefully against the uncertainties of its potential long-term benefits. This is why the committee has recommended the drug be made available for an initial period of five years, under strict conditions to allow more data to be gathered on its efficacy, before the guidance is reviewed and a further decision made on whether funding should be continued.”
Duchenne muscular dystrophy is a severe progressive disease linked to the X-chromosome, affecting mostly boys. There are between 60 and 70 children born with the disease in England each year and in around 6 – 9 children (13 percent) it is caused by a ‘nonsense mutation’. It causes insufficient production of the protein, dystrophin, that protects muscle from wasting.
The disease is present from birth and symptoms usually appear at around age 3. It leads to gradual decline in muscle function with children often using a wheelchair by early adolescence and eventually requiring artificial ventilation to breathe.
Ataluren works by allowing the body to read over the mutation in the DNA and continue to produce dystrophin. It is unclear how long it remains effective.
It is thought around 50 children could benefit from the drug during the five year managed access agreement.
The standard treatment is corticosteroids which can delay deterioration but can cause unwanted effects such as growth retardation, bone thinning, mood swings and weight gain.
Dr Peter Jackson, Chair of the NICE High Specialised Technologies Evaluation Committee said: “This was a difficult evaluation given the uncertain nature of the data and the high cost of the drug. However the committee recognised that this is a distinct disorder, striking children at a significant stage of their lives and that the drug is highly innovative because it allows the body to continue making an active form of the protein it is missing.
“But the committee could not have recommended ataluren without the agreement to limit its use to five years while more data are gathered. If those data show that the drug is less effective in the longer term and doesn’t provide good value, the NHS is not committed to funding the drug in the long-term.”
Filed Under: Drug Discovery