NICE Approves First-of-its-Kind Drug for Spinal Muscular Atrophy

Dawn O'Shea

November 19, 2021

About 1500 people with spinal muscular atrophy (SMA) could be set to benefit from a new first-of-its-kind treatment, following an agreement between NICE and the manufacturers, Roche.

In draft guidance, NICE has recommended risdiplam (Evrysdi) as an option for treating 5q SMA in children aged 2 months and older with a clinical diagnosis of SMA types 1, 2, or 3 or with pre-symptomatic SMA and one to four copies of the survival of motor neuron 2 (SMN2) gene.

The treatment has not been approved for routine use in the NHS but is being made available as part of a managed access agreement (MAA) between Roche and NHS England and NHS Improvement.

The MAA will allow clinicians to use the drug while more data is collected to address uncertainties about the evidence, which was highlighted by NICE in an earlier draft.

In draft guidance issued in June 2021, NICE chose not to recommend risdiplam. The guidance recognised that risdiplam is the first oral-administered SMA treatment, meaning that it could be administered in the patient’s home. Whilst the agency acknowledged that clinical trials demonstrate that risdiplam improves motor function, it said the long-term benefits are uncertain.

At that time, that the cost-effectiveness estimates were substantially higher than the range normally considered a cost-effective use of NHS resources. In the case of type 1, this was despite agreeing that risdiplam could be considered a life-extending treatment at the end of life.

Study details

The main clinical-effectiveness evidence for risdiplam came from two clinical studies:

SUNFISH, which is a randomised, double-blind, multicentre, phase 2, placebo-controlled trial for the first 12 months of treatment, after which people in the placebo arm could switch to the risdiplam arm. It included 180 people aged 2-25 years with types 2 or 3 SMA. Part 2 of SUNFISH excluded patients who had any previous treatment, and also those with type 3 SMA who were able to walk.

FIREFISH is a single-arm study of 41 patients aged 1-7 months with type 1 SMA and two SMN2 copies. It excluded patients who had previous treatment and those having chronic ventilation.

There are also two ongoing studies. RAINBOWFISH is a phase 2, single-arm study of babies 6 weeks or under with genetically-diagnosed SMA but did not have symptoms. JEWELFISH is an open-label, single-arm study for SMA types 1, 2, and 3 in people of 6 months to 60 years who had previously enrolled in the MOONFISH study or who had previously had nusinersen, onasemnogene abeparvovec or olesoxime.

The clinical evidence shows that risdiplam improves the ability to sit up, stand or walk for people with type 1, 2, and 3 SMA and that it may be effective for people before they start showing symptoms. There is also some evidence suggesting that people with type 1 SMA live for longer on risdiplam. However, there is no direct evidence comparing risdiplam with best supportive care for type 1 SMA, and there is no long-term evidence of benefit for risdiplam overall.

The MAA scheme will allow these data to be collected through the NHS.

Meindert Boysen, deputy chief executive and director of the Centre for Health Technology Evaluation at NICE, said: "We are pleased that there will now be the option of a convenient oral treatment for people with SMA that can be administered at home. This will not only be less burdensome, and therefore have a positive impact on the lives of both people with SMA and their caregivers, but it will also reduce the treatment administration requirements for the NHS."

"In practical terms, the availability of an oral drug should lead to greater adherence to treatment, along with giving access to a treatment to those who aren’t able to have other currently recommended options."

Risdiplam is an SMN2 mRNA splicing modifier designed to treat SMA caused by mutations in chromosome 5q that lead to SMN protein deficiency. It works to increase and sustain the production of the SMN protein, which is critical for maintaining healthy motor neurons.


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