Sapphire Trial Results and Updates
Sapphire Trial Results and Updates
Last updated: 5th October 2026
Apitegromab: The SAPPHIRE study
The Phase 3 Sapphire study involved 188 people aged 2–21 with Type 2 or Type 3 SMA who were unable to walk independently. Everyone taking part was already receiving an existing SMA treatment, either nusinersen (Spinraza) or risdiplam (Evrysdi).
This means apitegromab is being investigated as an additional treatment alongside an existing SMA treatment, rather than replacing it.
Researchers measured changes in participants’ motor function, their ability to carry out different physical movements, using established SMA motor-function assessments.
What did the trial find?
The main part of the study looked at children aged 2–12 years and measured changes in motor function over 12 months using the Hammersmith Functional Motor Scale Expanded (HFMSE).
When the two apitegromab dose groups were combined, children receiving apitegromab had an average 1.8-point advantage on the HFMSE compared with those receiving placebo. This difference was statistically significant.
Importantly, the difference wasn’t simply about large improvements in the apitegromab group. On average, motor function remained slightly improved in those receiving apitegromab, while it declined in the placebo group. This suggests that maintaining function as well as gaining function may be an important part of the treatment’s effect.
There is an important qualification. When researchers looked specifically at the 20 mg/kg dose compared with placebo, the difference did not reach statistical significance. So, although the overall primary analysis was positive, the results are more nuanced than simply saying that every apitegromab group showed a significant improvement.
What about safety?
Overall, apitegromab was reported to be generally well tolerated.
The number and severity of side effects were similar between people receiving apitegromab and those receiving placebo. Commonly reported events included fever, colds and respiratory infections, cough, vomiting and headache. No participants stopped treatment because of side effects.
Why is this research important?
One of the particularly interesting aspects of this study is the different way apitegromab approaches SMA.
Existing treatments have transformed the outlook for many people with SMA, but they do not necessarily restore muscle function that has already been affected. Some people continue to experience significant muscle weakness despite receiving an SMN-targeting treatment.
SAPPHIRE provides evidence that targeting the muscles themselves, alongside treating the underlying SMN deficiency, could potentially offer additional benefit.
What does this mean for the SMA community?
These are encouraging research findings, but they need to be viewed in context.
The study was specifically conducted in non-ambulant children and young people with Type 2 or Type 3 SMA who were already taking Spinraza or Evrysdi. The results therefore cannot automatically be applied to everyone living with SMA, including adults or people with different levels of mobility.
The average difference seen on the motor-function scale was also relatively modest. However, in SMA, even maintaining abilities or achieving relatively small changes in movement can potentially be meaningful in everyday life. Exactly what these changes mean for individuals, for example, for independence and day-to-day activities, is an important part of understanding the longer-term impact of treatment.
Overall, the study provides important evidence that combining treatments which target different aspects of SMA may be a promising direction for future treatment.