Pioneering gene-silencing therapy is approved by NHS

Pioneering gene-silencing therapy that offers hope for patients with an ultra-rare hereditary disease is approved by NHS

  • Patisiran, brand name Onpattro, blocks the activity of a rogue gene in the liver
  • Gene causes hereditary transthyretin-mediated amyloidosis 
  • Condition affects everything from heart rate and vision to limb movement 

A pioneering ‘gene-silencing’ therapy has been approved for NHS use in England to treat patients with an ultra-rare disease.

Patisiran, which is marketed under the brand name Onpattro, is a cutting-edge drug that blocks the activity of the mutated TTR gene in the liver.

Faulty TTR is responsible for the hereditary condition transthyretin-mediated amyloidosis (hATTR amyloidosis), which is thought to affect just 100 people in the UK.

Many patients die just five years after being diagnosed, with hATTR amyloidosis affecting everything from their heart rate and vision to limb movement and ability to swallow. 

Patisiran got the green light after a trial showed it improved symptoms in 56 per cent of more than 200 patients.

Officials claimed the drug, which costs up to £300,000 ($371,030) annually per patient, is cost effective considering the ‘rarity and severity of the condition’.

Doctors and patients alike welcome the news, calling it an ‘important step forward’ and ‘momentous day’.

Patisiran (pictured), which is marketed under the brand name Onpattro, is a cutting-edge drug that blocks the activity of the mutated TTR gene in the liver. Faulty TTR is responsible for the hereditary condition transthyretin-mediated amyloidosis (hATTR amyloidosis)

Patisiran has been approved by The National Institute for Health Care Excellence (NICE) to treat adult patients with stage one or two polyneuropathy.

Polyneuropathy is defined as damage to the peripheral nerves outside of the brain and spinal cord.

Professor Philip Hawkins, head of the National Amyloidosis Centre at London’s Royal Free Hospital, said NICE’s decision ‘marks an important step forward’.

‘Patisiran has shown in its main clinical study that it can halt or even improve potentially debilitating symptoms of this disease in the majority of patients,’ he said.

‘This means we now have a real possibility of preserving quality of life for eligible patients for longer than has so far been possible.’

hATTR amyloidosis, which can be inherited from either parent, causes the sticky amyloid protein to build up in a patient’s organs and around their nerves.  

Vincent Nicholas, who has hATTR amyloidosis, claims the disease has ‘decimated’ his family.

‘My mum had five siblings and they all died of it,’ he told the BBC. ‘There are five of us, three of us have it and one has died.’

Mr Nicholas’ symptoms started with pins and needles in his hands and feet. 

His brother Neil, who is also a sufferer, claims his legs have gradually become numb below the knees. Most patients eventually require a wheelchair to get about.

WHAT IS TRANSTHYRETIN-MEDIATED AMYLOIDOSIS?

Transthyretin-mediated amyloidosis (hATTR amyloidosis) is a hereditary condition that causes a deadly build-up of a toxic protein in a patient’s body. 

It is said to affect 100 people in the UK and no more than 6,400 in the US. 

The condition comes about due to mutations in the TTR gene. 

TTR makes the protein transthyretin. 

Genetic mutations cause transthyretin to not be made correctly. 

Faulty transthyretin then folds up to form the sticky protein amyloid.

Amyloid accumulates in a patient’s body, which leads to nerve and tissue damage.

The faulty TTR gene can be inherited from just one parent or occur spontaneously.

A hATTR-amyloidosis sufferer has a 50 per cent chance of having a child with the condition. 

Symptoms start in adulthood and get worse over time.

Where symptoms occur depend on where amyloid accumulates.

A build-up in the nerves of the peripheral system causes a loss of sensation in the lower limbs, hands and feet.

It can also affect involuntary body functions, such as heart rate, blood pressure and digestion.

Patients often also report impotence, diarrhoea or constipation, unexplained weight loss, and dry eyes and mouth. 

Once the condition progresses, symptoms can include stroke, seizures, dementia and congestive heart failure. 

The ‘gold standard’ treatment used to be liver transplantation, which removes the main source of amyloid from the body.

But amyloid can still build-up in the heart, brain and eyes. 

Patients may later require a heart or kidney transplant.

They may also need to have the liquid part of their eyes replaced.

In July 2019, NHS England approved the drug patisiran, marketed under the brand name Onpattro, after it was found to improve patients’ symptoms.

Patisiran works by preventing a short strand of our genetic code, known as messenger RNA, from passing on information to our DNA.

This ‘silences’ the gene that causes toxic levels of transthyretin to accumulate in the body.

Patisiran also got the green light from the Food and Drugs Administration in the US. 

Source: National Center for Advancing Translational Sciences 

Mr Nicholas, 59, of Redlynch, Wiltshire, said: ‘This is a momentous day for all amyloidosis suffers and their families within England.

‘No longer will any patient have to endure a liver transplant and our children will not have to suffer or make life changing choices as I have had to.’

Patisiran is the first treatment of its type in the world to be approved for hATTR amyloidosis.

It works by preventing a short strand of our genetic code, known as messenger RNA, from passing on information to our DNA.

This ‘silences’ the gene that causes toxic levels of amyloid to accumulate in the body.

After patisiran got the green light from the Food and Drugs Administration in the US, it was licensed by European and UK regulators last year.

A clinical trial for patisiran, called Apollo, involved 225 hATTR amyloidosis sufferers with polyneuropathy from 19 countries.

The US company Alnylam Pharmaceuticals, which manufactures the drug, found 56 per cent of the participants saw an improvement to their neuropathy symptoms and quality of life up to 36 months later.

This is compared to just four per cent of the patients who were treated with placebo.

Carlos Heras-Palou, a surgeon at the Royal Derby Hospital, who was involved in the trial, told the BBC: ‘This is making a disease that was previously untreatable, treatable.

‘I’ve been watching these patients get worse for 25 years, I know families that have been devastated by this disease.’ 

It is understood 20 people in the UK have been treated with patisiran so far. 

The drug is administered once every three weeks by intravenous infusion.

According to NICE, Alnylam has a ‘commercial arrangement’ which ‘makes patisiran available to the NHS with a discount’. 

The size of this discount has been kept confidential.

A NICE spokesman said: ‘The committee was aware of the uncertainty around the cost-effectiveness estimates for patisiran.

‘However, it acknowledged there were additional factors that should be taken into consideration in its decision making, including the rarity and severity of the condition.

‘[And] the considerable effect the condition has on families and carers, the size of the health benefits provided by patisiran, and the unique and innovative nature of the treatment.

‘The committee concluded that, considering all these factors, it was able to recommend patisiran as an option for treating hATTR amyloidosis.’

Patisiran was approved by the Scottish Medicines Consortium a couple of weeks ago.

Wales and Northern Ireland are expected to follow suit, the BBC reported. 

Carlos Heras-Palou, a spokesperson for the UK ATTR Amyloidosis Patients’ Association, added: ‘Today’s announcement has the potential to change the lives of families across the UK who are affected by this cruel disease.

‘[It offers] them an option that could reduce the burden of symptoms that can be crippling to many. 

‘This condition also carries a huge psychological toll, with many patients anxious that they may have passed on the faulty gene to children or grandchildren. 

‘The availability of patisiran is welcome news and will help provide important reassurance for patients today, as well as for those who may need treatment in the future.’

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