New treatment options are being developed for both wild-type and hereditary ATTR (hATTR) amyloidosis and there has been encouraging progress in recent years with the arrival of therapies that can help certain forms of the disease, or slow certain symptoms.
At present there is no cure for either wild-type or hATTR amyloidosis; however, there is much that can be done to help people living with the condition.
Treatment of amyloidosis usually focuses on either:
• Reducing the production of amyloid
• Supporting the function of organs containing amyloid
Reducing amyloid production usually involves trying to control the amount of abnormal TTR protein in the body – as this is what goes on to form amyloid. If you control abnormal TTR protein, the hope is that:
• Existing amyloid deposits become smaller
• New amyloid deposits stop appearing
• Organ function will often be preserved and may recover in some cases
Treatment
New treatment options are being developed for both wild-type and hereditary ATTR (hATTR) amyloidosis and there has been encouraging progress in recent years with the arrival of therapies that can help certain forms of the disease, or slow certain symptoms.
At present there is no cure for either wild-type or hATTR amyloidosis; however, there is much that can be done to help people living with the condition.
Treatment of amyloidosis usually focuses on either:
• Reducing the production of amyloid
• Supporting the function of organs containing amyloid
Reducing amyloid production usually involves trying to control the amount of abnormal TTR protein in the body – as this is what goes on to form amyloid. If you control abnormal TTR protein, the hope is that:
• Existing amyloid deposits become smaller
• New amyloid deposits stop appearing
• Organ function will often be preserved and may recover in some cases
Reducing the amount of abnormal TTR protein produced in the body
Genetic based therapies
Two recently developed genetic therapies (commonly referred to as gene-silencing therapies in the news), called patisiran and inotersen, aim to ‘silence’ the TTR gene in the liver cells – this gene acts as a blueprint to make TTR protein.
This means that TTR protein (both abnormal and healthy) is simply not produced.
Patisiran belongs to a class of medicines called small interfering RNA, whereas inotersen belongs to the antisense oligonucleotide drug class. In clinical trials in patients with hATTR amyloidosis both these drugs improved neuropathy symptoms, quality of life, daily activities and disability.
Patisiran is also called Onpattro – you can read more about this medicine and the results of the clinical studies on the website of the European Medicines Agency here.
Inotersen is also called Tegsedi – you can read more about this medicine and the results of clinical studies on the website on the EMA website here.
Both patisiran and inotersen have been approved by the European Medicines Agency and the U.S. Food and Drug Administration (FDA) for treating neuropathy caused by hATTR amyloidosis and are licensed for use in the UK and Ireland for this purpose.
The availability of these medicines on the NHS is determined by various health authorities in the country where you live.
You can see the latest NICE guidance on the use of patisiran in England, Wales and Northern Ireland here and for inotersen here.
You can see the latest SMC recommendation for the use of patisiran in Scotland here and for inotersen here.
As well as treatment for neuropathy there are some clinical studies investigating the effects of these medicines on cardiac function in both hATTR and wild-type amyloidosis.
Reducing the amount of abnormal TTR protein produced in the body
Genetic based therapies
Two recently developed genetic therapies (commonly referred to as gene-silencing therapies in the news), called patisiran and inotersen, aim to ‘silence’ the TTR gene in the liver cells – this gene acts as a blueprint to make TTR protein.
This means that TTR protein (both abnormal and healthy) is simply not produced.
Patisiran belongs to a class of medicines called small interfering RNA, whereas inotersen belongs to the antisense oligonucleotide drug class. In clinical trials in patients with hATTR amyloidosis both these drugs improved neuropathy symptoms, quality of life, daily activities and disability.
Patisiran is also called Onpattro – you can read more about this medicine and the results of the clinical studies on the website of the European Medicines Agency here.
Inotersen is also called Tegsedi – you can read more about this medicine and the results of clinical studies on the website on the EMA website here.
Both patisiran and inotersen have been approved by the European Medicines Agency and the U.S. Food and Drug Administration (FDA) for treating neuropathy caused by hATTR amyloidosis and are licensed for use in the UK and Ireland for this purpose.
The availability of these medicines on the NHS is determined by various health authorities in the country where you live.
You can see the latest NICE guidance on the use of patisiran in England, Wales and Northern Ireland here and for inotersen here.
You can see the latest SMC recommendation for the use of patisiran in Scotland here and for inotersen here.
As well as treatment for neuropathy there are some clinical studies investigating the effects of these medicines on cardiac function in both hATTR and wild-type amyloidosis.
Tafamidis
Tafamidis, is a TTR stabiliser. It attaches to TTR, which prevents the protein from breaking up, thereby stopping the formation of amyloid and slowing down the progression of the nerve disease.
You can read more information about tafamadis and the results of clinical studies on the EMA’s website here.
Tafamadis is not currently widely available on the NHS. You can see the latest guidance from NICE on its use in England and Wales here and from the SMC in Scotland here.
Tafamidis
Tafamidis, is a TTR stabiliser. It attaches to TTR, which prevents the protein from breaking up, thereby stopping the formation of amyloid and slowing down the progression of the nerve disease.
You can read more information about tafamadis and the results of clinical studies on the EMA’s website here.
Tafamadis is not currently widely available on the NHS. You can see the latest guidance from NICE on its use in England and Wales here and from the SMC in Scotland here.
Diflunisal
This drug belongs to a class of drugs called ‘non-steroidal anti-inflammatory drugs’ (NSAIDs). These drugs are in common use as painkillers, for conditions such as arthritis.
Diflunisal is bound by TTR in the blood. This binding is presumed to make the TTR protein less prone to breaking apart and going on to develop into amyloid.
Trials are currently underway to assess the effect of diflunisal on the progression of neuropathy and cardiomyopathy in patients with hATTR amyloidosis. Results from studies were encouraging, but the number of patients involved was small and the extent of benefit was modest. The trial involved 130 patients with hereditary ATTR amyloidosis that affected the nerves, 64 of whom received diflunisal for two years while 66 received a placebo (dummy pills).
The rate of progression of neuropathy was slower in the patients who received diflunisal than in those who did not. Results of trials of diflunisal in cardiac ATTR amyloidosis are not yet available. It is important to note that NSAIDs such as diflunisal may have serious side effects, which may be especially dangerous in patients who are already unwell with amyloidosis.
These side effects include:
- Bleeding from the stomach and gut.
- Worsening of kidney function.
- Worsening of heart failure.
Diflunisal use for ATTR amyloidosis is an ‘off-label’ indication, and only amyloidosis specialists should prescribe it.
Diflunisal
This drug belongs to a class of drugs called ‘non-steroidal anti-inflammatory drugs’ (NSAIDs). These drugs are in common use as painkillers, for conditions such as arthritis.
Diflunisal is bound by TTR in the blood. This binding is presumed to make the TTR protein less prone to breaking apart and going on to develop into amyloid.
Trials are currently underway to assess the effect of diflunisal on the progression of neuropathy and cardiomyopathy in patients with hATTR amyloidosis. Results from studies were encouraging, but the number of patients involved was small and the extent of benefit was modest. The trial involved 130 patients with hereditary ATTR amyloidosis that affected the nerves, 64 of whom received diflunisal for two years while 66 received a placebo (dummy pills).
The rate of progression of neuropathy was slower in the patients who received diflunisal than in those who did not. Results of trials of diflunisal in cardiac ATTR amyloidosis are not yet available. It is important to note that NSAIDs such as diflunisal may have serious side effects, which may be especially dangerous in patients who are already unwell with amyloidosis.
These side effects include:
- Bleeding from the stomach and gut.
- Worsening of kidney function.
- Worsening of heart failure.
Diflunisal use for ATTR amyloidosis is an ‘off-label’ indication, and only amyloidosis specialists should prescribe it.
Information on clinical trials in ATTR amyloidosis
Clinical studies may be an option for patients with ATTR amyloidosis. For information on ongoing trials at the NAC, please visit here or ask your doctor or clinical team for more information. You can also visit https://clinicaltrials.gov/ which has more information on clinical studies, although these may not be available to UK patients.
Information on clinical trials in ATTR amyloidosis
Clinical studies may be an option for patients with ATTR amyloidosis. For information on ongoing trials at the NAC, please visit here or ask your doctor or clinical team for more information. You can also visit https://clinicaltrials.gov/ which has more information on clinical studies, although these may not be available to UK patients.
Liver transplantation
All the TTR in the blood, which forms amyloid deposits everywhere except in the eye and the blood vessels around the brain, is made in the liver.
In the past, liver transplantation was a treatment option for some patients with hATTR amyloidosis. Since the advent of the new drugs, liver transplantation is rarely recommended in the UK.
Find out more about supportive treatment for heart disease:
Find out more about managing neuropathy:
Liver transplantation
All the TTR in the blood, which forms amyloid deposits everywhere except in the eye and the blood vessels around the brain, is made in the liver.
In the past, liver transplantation was a treatment option for some patients with hATTR amyloidosis. Since the advent of the new drugs, liver transplantation is rarely recommended in the UK.
Find out more about supportive treatment for heart disease:
Find out more about managing neuropathy: