Evrysdi

Pharmaceutical company: Roche

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.

Eligible people with SMA can access Evrysdi through a Managed Access Agreement (MAA) in England, Wales and Northern Ireland. This agreement means Evrysdi is currently available on the NHS at a discounted price.

People with SMA in Scotland can access Evrysdi through the NHS.

In 2021, the National Institute for Health and Care Excellence (NICE) recommended Evrysdi for use on the NHS in England, Wales and Northern Ireland. However, NICE requested the collection of additional data to confirm how well Evrysdi works. NICE therefore made Spinraza available through a Managed Access Agreement (MAA), so that eligible people with SMA could access the treatment while the additional data was collected. Once additional data is collected, NICE will reassess Evrysdi and decide whether it should be permanently made available on the NHS.

Evrysdi is being assessed alongside a second SMA treatment, Spinraza (also known as nusinersen), in a process called a Multi-Technology Appraisal (MTA). The treatments are being assessed together as they are both designed to increase SMN protein levels, and the assessments will cover similar topics. Read about the NICE process of Evrysdi and Spinraza.

In February 2022, Evrysdi was accepted for use within NHS Scotland. Read about the Scottish Medicines Consortium (SMC)’s assessment of Evrysdi.

NICE are currently reassessing Evrysdi, with a decision expected in 2026. As there have been some unexpected delays with the assessment, NICE are planning to extend the MAA. This means current and new patients can still access Evrysdi while the assessment continues.

We were heavily involved in the first assessment of Evrysdi by NICE, which led to access of Evrysdi through the MAA. We are also a member of the Managed Access Oversight Committee (MAOC) which oversees the operation of the agreement, including how the additional data is collected and the discussion of any potential changes to the eligibility criteria.

We are currently working in partnership with the charities SMA UK and Treat SMA throughout the NICE reassessment to make sure the experience and views of the SMA community continue to be heard.

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.

Last updated: 18/02/2025