So far, we have played a role in making sure people can access ten treatments for five different muscle wasting and weakening conditions.
Duchenne muscular dystrophy treatments
About the treatment
Corticosteroids are thought to reduce damage to muscles by binding to receptors which reduce inflammation. However, when corticosteroids bind to these receptors, they also activate lots of other pathways which lead to a wide range of side effects.
Agamree binds to the same receptors as corticosteroids but avoids activating some pathways linked to corticosteroids side effects. This means Agamree can help reduce inflammation but may have fewer side effects. Agamree comes as a liquid that can be swallowed.
Availability
Agamree has been recommended as a treatment option for people aged four and over with Duchenne muscular dystrophy in the UK. Please contact your (or child’s) clinical team for more information.
For recommendations on the use of this treatment in England, Wales and Northern Ireland, please read the National Institute for Health and Care Excellence (NICE) guidance.
For recommendations on the use of this treatment in Scotland read the full Scottish Medicines Consortium (SMC) guidance.
Clinical trial results
Evidence from the phase 2b VISION-DMD clinical trial was used in the UK assessment of Agamree. This trial compared treatment with Agamree against both a placebo (dummy drug) and a corticosteroid often used to treat DMD (prednisone). 121 boys aged between four and six years old took part in the trial. They were randomly assigned to receive either one of two doses of Agamree (60 participants), prednisone (31 participants) or placebo (30 participants).
After 24 weeks, boys who received Agamree were able to stand quicker compared to when they started the study, as measured by the time to stand from supine velocity (TTSTAND) test. They also showed improvements compared to the boys who received the placebo.
Boys who received Agamree scored similarly to those who received prednisone on movement measurements, including the NorthStar Ambulatory Assessment, six-minute walk test (6MWT) and TTSTAND. This suggests that Agamree and prednisone have a similar effect in boys over four years with DMD.
Results from the trial have also suggested that Agamree has less of an impact on growth than other corticosteroids. However, other side effects were still reported.
About the treatment
As our muscles are subjected to a lot of wear and tear, our cells have built in ways to help repair muscles and keep them functioning as they should. A molecule called histone deacetylase plays a key role in these repair processes. In people with Duchenne muscular dystrophy, histone deacetylase is overactive, reducing muscle repair.
Duvyzat blocks the activity of histone deacetylase, to help improve muscle repair. It aims to reduce inflammation and the build-up of scar tissues, and ultimately slow progression. Duvyzat comes as a liquid that can be swallowed.
Availability
Duvyzat has been recommended as a treatment option for people aged six and over with Duchenne muscular dystrophy in the UK. Please contact your (or child’s) clinical team for more information.
For recommendations on the use of this treatment in England, Wales and Northern Ireland, please read the National Institute for Health and Care Excellence (NICE) guidance.
For recommendations on the use of this treatment in Scotland read the full Scottish Medicines Consortium (SMC) guidance.
Clinical trial results
The phase 3 EPIDYS clinical trial included 179 boys with DMD, aged six and older and could walk. They were randomly assigned to receive Duvyzat (118 participants) or placebo (dummy drug, 61 participants).
After 72 weeks, all participants’ four-stair climb assessment results got worse, suggesting their ability to move reduced. However, the decline in movement was statistically significantly smaller in those who received Duvyzat compared to those who received the placebo. This suggests Duvyzat is likely to slow progression. Duvyzat was found to be safe. Some participants had a reduction in blood platelets (which help with clotting and to stop bleeding), but this was managed by reducing the dose.
Safety
Duvyzat can sometimes cause side effects that doctors need to monitor closely, which is why regular check-ups are important. With the right care and monitoring, doctors can often help manage these effects, allowing treatment to continue or, if needed, deciding when it’s best to stop.
About the treatment
Our genes are the instruction manuals to make proteins. Proteins play an important role in all the tasks our cells do. Just like how there is a full stop to show that a sentence has ended, genes also have stop signals to show when the instructions for a protein have ended.
Some people with Duchenne muscular dystrophy have a specific change in the gene for the dystrophin protein, called a nonsense change (scientists call it a ‘nonsense mutation’). This causes the stop signal to be in the wrong place, shortening the instructions for dystrophin and preventing functional dystrophin from being made.
Translarna tells the cell to ignore the early stop signal so that the full-length, working dystrophin protein is made. Translarna comes in a sachet and can be swallowed after mixing it in a liquid or semi-solid food.
Availability
Translarna has been recommended as a treatment option for children aged two and over with Duchenne muscular dystrophy caused by a nonsense genetic change living in England, Wales and Northern Ireland. Please contact your (or child’s) clinical team for more information. For recommendations on the use of this treatment in England, Wales and Northern Ireland, please read the National Institute for Health and Care Excellence NICE guidance.
Translarna has not been recommended for use on the NHS in Scotland. However, there are processes where NHS boards can consider individual requests if a doctor believes a treatment would be appropriate. Read more about why Translarna was not accepted for use on the NHS in Scotland in our blog or read the full guidance from the Scottish Medicines Consortium (SMC).
Clinical trial results
Translarna has been tested in several clinical trials and has been shown to be safe in all these trials.
In the phase 2 trial, 174 participants, aged between 5-20 years old, were randomly assigned to receive either one of two doses of Translarna or placebo (dummy drug). After 48 weeks, participants who received the lower dose (40 mg/kg/day) of Translarna showed a slowing in the rate they lost their ability to walk, compared to placebo. On average Translarna treated participants walked 30-meters further than those on placebo in the six-minute walk distance test (6MWD).
In the phase 3 trial, 230 participants, aged between 7-16 years old, were randomly assigned to receive Translarna (40 mg/kg/day) or placebo. After 48 weeks, participants who received Translarna showed a slowing in the rate they lost their ability to walk, compared to placebo. On average Translarna treated participants walked 13-meters further than those on placebo in the six-minute walk distance test (6MWD). However, the researchers could not confirm that these results were not due to chance. Researchers refer to this as ‘not statistically significant’.
Real-world evidence
Since Translarna has been approved for use around the world, additional data has been collected while it has been routinely used. This is known as ‘real-world evidence’. The STRIDE database collected data from people taking Translarna, with an average use of five years. To analyse the impact of Translarna over a longer period, the researchers compared people from the STRIDE database with people with DMD who had never received Translarna.
To do this the researchers used data from a natural history study. These studies follow people living with DMD who receive usual standard of care, including treatment with corticosteroids, but not Translarna. The researchers made sure the participants from the STRIDE database and the natural history study had similar characteristics, such as age, so that a more accurate comparison could be made.
The researchers found that participants who received Translarna, lost the ability to walk at a later age than those receiving usual standard of care. Those who received standard of care were, on average, able to walk up to age 13. Translarna treated were, on average, able to walk up to age 17.
It is important to note that real-world evidence does come with limitations and potential for bias. Placebo controlled clinical trials are the gold standard in gathering evidence to determine if a treatment has a beneficial effect.
Myasthenia gravis treatments
About the treatment
To move, signals must be sent from the brain, down specialised cells called nerves to the muscle. Acetylcholine receptors and a protein called MuSK play a key role in passing the signal from nerve cells to the muscle. In myasthenia gravis, the immune system attacks the acetylcholine receptors, and in a smaller percentage of cases, the MuSK protein. This means the nerve cells struggle to send strong signals to muscles, leading to muscle weakness.
Rystiggo works by reducing the effect of the immune system on the acetylcholine receptors and MuSK protein. Specifically, Rystiggo reduces the levels of molecules called antibodies. Antibodies are produced by the immune system to protect the body from foreign substances, like bacteria. However, sometimes these antibodies can target our own cells. By reducing the levels of the antibodies, stronger signals should be able to be sent to the muscles.
Rystiggo come as a liquid and is administered slowly under the skin (subcutaneous infusion).
Availability
Rystiggo has been recommended as a treatment option for people living with refractory generalised myasthenia gravis living in England, Wales and Northern Ireland. Please contact your (or child’s) clinical team for more information. If you’re struggling to access Rystiggo, please contact us on campaigns@musculardystrophyuk.org. For recommendations on the use of this treatment in England, Wales and Northern Ireland, please read the National Institute for Health and Care Excellence (NICE) guidance.
Rystiggo is not yet routinely available on the NHS in Scotland and there currently isn’t a timeline for the assessment by the Scottish Medicines Consortium (SMC), who decide if a treatment is available on the NHS in Scotland. You may be available through an early access scheme. For more information, please get in touch with your clinician.
Clinical trial results
Rystiggo was tested in the phase 3 MycarinG trial. 200 participants, aged over 18 years old, with a myasthenia gravis activities of daily living (MG-ADL) score of at least three took part in the trial. The MG-ADL score measures the impact of the condition on a person’s daily function, such as talking, swallowing and getting up from a chair. The score can range from zero to 24, with a lower score means symptoms are less severe.
Participants were randomly assigned to receive one of two doses of Rystiggo (133 participants) or placebo (dummy drug, 67 participants). All participants tested positive for the antibodies which attack acetylcholine receptors or MuSK protein. Rystiggo was found to be safe. After 43 days, more participants who received Rystiggo showed improvements in the MG-ADL scale, compared to those who received the placebo.
68% of participants who received Rystiggo had a reduction of at least two points, compared to 28% of participants who received the placebo. A reduction of two points is considered to be beneficial (clinically meaningful) to people living with the condition. This may mean people with the condition are able to complete daily tasks they were unable to before, such as brush their hair or get up out of a chair without assistance.
Myotonia treatments
About the treatment
Namuscla works by blocking a channel in the membrane of muscle cells that allow sodium ions (electrically charged particles) to pass in and out. Sodium ions play a role in the communication of electrical signals between the brain and muscles, which tell a muscle when to contract and relax.
In people with non-dystrophic myotonic disorders, the channels are over-active. This means repeated electrical signals are sent to the muscle. This causes muscles to take longer to relax, become tense and stiff. Blocking the channels reduces the repeated signals and should reduce muscle stiffness.
Namuscla comes as a capsule that can be swallowed.
Availability
Namuscla has been recommended as an option for treating the symptoms of myotonia in adults with non-dystrophic myotonic disorders in the UK and is available on the NHS. Please consult your clinical team for more information.
For recommendations on the use of this treatment in England, Wales and Northern Ireland, please read the National Institute for Health and Care Excellence (NICE) guidance.
For recommendations on the use of this treatment in Scotland, please read the full Scottish Medicines Consortium (SMC) guidance.
Clinical trial results
Evidence from the phase 3 MYOMEX clinical trial was used in the UK assessment of Namuscla. This was a two-part trial. In part one, participants were randomly assigned to receive either the treatment (12 participants) or the placebo (dummy drug, 13 participants) for 18-22 days. All participants then stopped taking the treatment or placebo for 4-8 days. In part two, the participants crossed over, meaning those who originally took the treatment received the placebo and vice versa, for another 18-22 days.
When participants took Namuscla, they reported a statistically significant improvement (78%) in stiffness compared to placebo, measured by the visual analogic scale (VAS). This is a self-reported scale from “no stiffness at all” to “worst possible stiffness”. This suggests that it is likely Namuscla improves stiffness.
Participants who received Namuscla also reported a significant improvement in quality of life through the INQoL questionnaire. This assesses the impact of the condition and symptoms on different areas of their life, such as pain, weakness, independence and social relationships. Namuscla was also found to be safe.
Pompe disease treatments
About the treatment
Cells need energy to function properly. We get energy from food, and it is stored within the body as glycogen. A molecule in the body, called alpha-glucosidase breaks down glycogen to release glucose, providing energy for cells. In people with late-onset Pompe disease, alpha-glucosidase is missing. This leads to a build-up of glycogen, reducing the amount of energy cells get and causing muscle weakness.
Pombiliti mimics alpha-glucosidase, reducing the build-up of glycogen by breaking it down to release glucose. Opfolda is used alongside Pombiliti as it helps cells affected by late-onset Pompe disease absorb cipaglucosidase more easily.
Pombiliti is administered slowly into the bloodsteam (intravenous infusion). Opfolda comes as a capsule and is swallowed an hour before administration of Pomniliti.
Availability
Pombiliti with Opfolda has been recommended as a treatment option for Pompe disease in the UK and is available on the NHS. Please consult your clinical team for more information.
For recommendations on the use of this treatment in England, Wales and Northern Ireland, please read the National Institute for Health and Care Excellence (NICE) guidance.
For recommendations on the use of this treatment in Scotland, please read the full Scottish Medicines Consortium (SMC) guidance.
Clinical trial results
Evidence from the phase 3 PROPEL clinical trial was used in the UK assessment of Pombiliti with Opfolda. In the trial, participants were randomly assigned to receive the treatment (85 participants) or a similar treatment for Pompe disease (Myozyme, also known as alglucosidase alfa) with a placebo (dummy drug) (40 participants). The trial found Pombiliti with Opfolda was safe.
After 52 weeks, participants who received Pombiliti with Opfolda showed improvements in measurements of walking when compared to participants who received Myozyme and placebo. However, the researchers could not confirm that the improvements in walking were not due to chance. Researchers refer to this as ‘not statistically significant’.
The results of a measurement of breathing (forced vital capacity (FVC%) predicted) got worse in all participants. However, the decline in FVC% predicted was statistically significantly smaller in those who received Pombiliti with Opfolda compared to those who received Myozyme and placebo. This suggests short-term treatment with Pombiliti with Opfolda is likely to be more beneficial, for some symptoms, than treatment with Myozyme.
Data was collected to monitor the long-term effects of Pombiliti with Opfolda. After 48 months, improvements in walking and breathing measurements were reported. However, this data was not compared against a placebo, meaning its use in confirming any long-term benefits may be limited.
About the treatment
Cells need energy to function properly. We get energy from food, and it is stored within the body as glycogen. A molecule in the body, called alpha-glucosidase breaks down glycogen to release glucose, providing energy for cells. In people with late-onset Pompe disease, alpha-glucosidase is missing. This leads to a build-up of glycogen, reducing the amount of energy cells get and causing muscle weakness.
Nexviazyme mimics alpha-glucosidase, reducing the build-up of glycogen by breaking it down to release glucose. Nexviazyme comes as a liquid and is administered slowly into the bloodstream (intravenous infusion).
Availability
Nexviazyme has been recommended as a treatment option for Pompe disease in the UK and is available on the NHS. Please consult your (or child’s) clinical team for more information.
For recommendations on the use of this treatment in England, Wales and Northern Ireland, please read the National Institute for Health and Care Excellence (NICE) guidance.
For recommendations on the use of this treatment in Scotland, please read the full Scottish Medicines Consortium (SMC) guidance.
Clinical trial results
Evidence from the phase 3 COMET clinical trial was used in the UK assessment of Nexviazyme. This trial compared Nexviazyme to a similar treatment for Pompe disease, called Myozyme (also known as alglucosidase alfa). 100 participants with Pompe disease, aged between 16 – 78 years old, took part in the trial. Participants were either randomly assigned to receive Nexviazyme (51 participants) or Myozyme (49 participants). The trial found Nexviazyme was safe.
After 49 weeks, participants who received Nexviazyme showed improvements in measurements of breathing and walking. However, the researchers could not confirm that the improvements seen were not due to chance. Researchers refer to this as ‘not statistically significant’.
This means that the researchers cannot say for definite that treatment with Nexviazyme is more beneficial than treatment with Myozyme. However, there is no evidence to suggest Nexviazyme is less beneficial than Myozyme, suggesting that the treatments have a similar effect.
Spinal muscular atrophy treatments
About the treatment
Our genes act as the instructions to make proteins, which play a vital role in all the tasks our cells do. People with SMA lack some of the instructions (SM1 gene) needed to make a protein called ‘survival motor neuron’ (SMN). This protein is essential for the health and survival of nerve cells which help to control muscles.
There are ‘back up’ instructions (SM2 gene), which produces a smaller amount of working SMN protein. Evrysdi modifies how the ‘back up’ instructions are used to make the SMN protein, leading to increased levels of working SMN protein.
Evrysdi comes as a solution that can be swallowed. Roche have also developed a tablet form of Evrysdi which can be swallowed or dissolved in water.
Current status
Evrysdi has been recommended as a treatment option for people with spinal muscular atrophy in the UK. Please contact your (or child’s) clinical team for more information.
For recommendations on the use of this treatment in England, Wales and Northern Ireland, please read the National Institute for Health and Care Excellence (NICE) guidance.
For recommendations on the use of this treatment in Scotland, please read the full Scottish Medicines Consortium (SMC) guidance.
Clinical trial results
Evrysdi has been tested in many clinical trials, in people with type 1,2 and 3 SMA, as well as newborns who are pre-symptomatic. Pre-symptomatic means babies have a genetic change associated with SMA but are not yet showing symptoms. All the trials found Evrysdi to be safe.
Type 2 or 3 SMA
In the phase 3 SUNFISH trial, 231 participants with type 2 or 3 SMA, aged between 2 and 25 years were randomly assigned to receive Evrysdi (115 participants) or placebo (dummy drug, 59 participants). After 12 months, participants who received Evrysdi had improvements in motor function (ability to move, as measured by a series of tests called the MFM-32 score), compared to those who received the placebo. However, this was not statistically significant, meaning the researchers couldn’t confirm the results weren’t due to chance.
Type 1 SMA
In the FIREFISH trial, all 62 infants with type 1 SMA, aged between one and seven months old were given Evrysdi. There was no placebo, instead the researchers compared against natural history data. This is where infants with SMA are followed to gather information on the natural progression and impact of the condition. They have not received the treatment.
- After 12 months, almost a third (29%) of infants who received Evrysdi were siting without support for at least 5 seconds.
- Natural history data suggests that, without treatment, 5% of the infants would be expected to sit without support for at least 5 seconds.
- After 24 months, 61% of the infants who received Evrysdi could sit without support for at least 5 seconds, however this was not compared to any data from infants who didn’t receive the treatment.
Pre-symptomatic SMA
In the RAINBOWFISH trial, all 26 newborns with pre-symptomatic SMA (have a genetic change associated with SMA but are not yet showing symptoms) aged 16 – 41 days old, were given Evrysdi. There was no placebo, instead the researchers compared against natural history data.
- After 12 months, many (81%) of the infants who received Evrysdi were able to sit without support for at least 30 seconds.
- Natural history data suggests that, without treatment, infants with type 1 SMA would never be able to sit without support.
It is important to note that natural history data can come with some limitations. Placebo controlled clinical trials are the gold standard in gathering evidence to determine if a treatment has a beneficial effect, as they can make the evidence collected more reliable. However, researchers also consider how ethical it is to use a placebo when designing trials. It can also be difficult to find enough participants to carry out placebo controlled clinical trials for rare diseases.
About the treatment
Spinraza is a small piece of man-made genetic material (called an antisense oligonucleotide). It targets the ‘back up’ SMN2 (survival motor neuron) gene so that it produces full-length, functional SMN protein. This protein is essential for the health of nerve cells which help to control muscles.
Spinraza comes as a liquid and is administered directly into the fluid around the spine and brain (cerebral spinal fluid) through an injection into the spine (lumbar puncture).
Availability
Spinraza has been recommended as a treatment option for people with spinal muscular atrophy in the UK. Please contact your (or child’s) clinical team for more information.
For recommendations on the use of this treatment in England, Wales and Northern Ireland, please read the National Institute for Health and Care Excellence (NICE) guidance.
For recommendations on the use of this treatment in Scotland, please read the full Scottish Medicines Consortium (SMC) guidance, for type 1 and type 2 and 3.
Our involvement
For over ten years the SMA community has tirelessly campaigned for access – we are proud to have worked alongside the community to ensure access. This involved working in partnership with charities SMA UK and Treat SMA, to ensure the experience and views of the SMA community were heard.
Clinical trial results
Spinraza has been tested in several clinical trials, including in babies and young children. In these trials Spinraza was found to be safe.
In the phase 3 ENDEAR trial, 122 infants with type 1 SMA aged under eight months were randomly assigned to receive Spinraza (81 participants) or placebo (dummy drug, 41 participants). The trial found that infants who received Spinraza had improved survival and motor function (measures of movement), compared to infants who received placebo. Over half (51%) of infants who received Spinraza reached a motor development milestone (such as rolling over, crawling), measured by the Hammersmith Infant Neurological Examination. None of the infants in the placebo group reached a motor milestone.
In the phase 3 CHERISH trial, 126 children aged between two and nine years, whose SMA symptoms started after six months of age took part in the trial. They were randomly assigned to receive Spinraza (84 participants) or placebo (dummy drug, 42 participants). After 15 months, children who received Spinraza showed improvements in completing activities related daily living, such as sitting, rolling and standing. This was measured by the Hammersmith Functional Motor Scale Expanded for SMA (HFMSE). Over half (57%) of children who received Spinraza increased their HFMSE score by at least three points from the start of the trial to month 15, compared to 26% of children who received placebo.
High dose regimen
Biogen has been studying a higher dose of Spinraza. This involves two starting doses of 50 mg given 14 days apart, followed by 28 mg every four months. Results from the Phase 2/3 DEVOTE trial suggest that, in children who hadn’t received treatment before, the higher dose helped improve movement compared to those who received a placebo (dummy drug) in an earlier Spinraza study. The trial also looked at children and adults who switched from the current dose to the higher dose, and their ability to move tended to improve after the switch.
About the treatment
Zolgensma targets the genetic cause of SMA by delivering a functional copy of the SMN1 (survival motor neuron) gene into nerve cells. This leads to the production of the SMN protein, which is missing in SMA. This protein is essential for the health of nerve cells which help to control muscles.
Zolgensma is a single-dose treatment, meaning it is only administered once. It comes as a liquid and is administered into the bloodstream (known as intravenous infusion).
Availability
Zolgensma has been recommended as a treatment option for both symptomatic and pre-symptomatic (where a baby has a genetic change associated with SMA but is not yet showing symptoms) SMA in the UK and is available on the NHS. Please consult your child’s clinical team for more information.
For recommendations on the use of this treatment in England, Wales and Northern Ireland, please read the National Institute for Health and Care Excellence guidance:
For recommendations on the use of this treatment in Scotland, please read the full Scottish Medicines Consortium (SMC) guidance
Clinical trial results
Zolgensma has been tested in many clinical trials. The key evidence used during its assessment for use in the UK was from the phase 1 START trial and phase 3 STR1VE-US. These studies generally enrolled babies with type 1 SMA who were six months or younger when they received Zolgensma and had not received other SMA treatments.
In these trials, babies who were given the now-approved dose of Zolgensma lived longer and had improved motor function (being able to control and coordinate muscle movement). In the STR1VE-US trial, most children (82%) did not require ventilation support by age 18 months, and more than half (59%) were able to sit unsupported for at least 30 seconds. Zolgensma was also found to be safe.
Children who received Zolgensma in the phase 1 START trial have been found to maintain the improvements in motor function for an average of 6.9 years. Further data is still being collected to monitor the long-term effects of Zolgensma.
Zolgensma has also been tested in babies who have a genetic change associated with SMA but are not yet showing symptoms (pre-symptomatic). These babies would be expected to develop SMA, so were treated with Zolgensma before 6 weeks of age. After two years, all children were still alive and did not need ventilation or feeding tube support. Many of the children reached developmental milestones, such as being able to stand or walk independently, within timeframes that are typical for children without SMA.
We’re here to support you
Our support services
Webinars, Information Days, and support groups for our muscle wasting community. Our life-changing support is here for you.
Call our helpline
Information
Advice for living with or caring for someone with a muscle wasting condition.