Topaz Trial Results and Updates
Topaz Trial Results and Updates
Page last updated: 5th October 2026
Apitegromab: The TOPAZ study
What did the study involve?
The Phase 2 study, called TOPAZ, included 58 people with Type 2 or Type 3 SMA, aged between 2 and 21 years.
Participants received apitegromab through an intravenous (IV) infusion every four weeks for 12 months. Most participants were also receiving nusinersen (Spinraza). 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 they find?
Overall, the researchers saw encouraging signs of improvement in motor function, although results varied between the different groups.
The most noticeable improvements were seen in the younger group of children with Type 2 SMA who had previously started treatment with Spinraza at a younger age.
In this group, children receiving the higher dose of apitegromab improved by an average of 7.1 points on the Hammersmith Functional Motor Scale (HFMSE) over 12 months. Improvements were also seen in the group receiving the lower dose.
Results were more modest in the older groups. Some people’s motor function improved or remained stable, while others did not experience an improvement.
What about safety?
Apitegromab was generally well tolerated during the study.
The most commonly reported issues included headaches, fever, coughs and respiratory infections. There were no deaths or serious adverse reactions considered to be caused by apitegromab during the study.
What does this mean for people living with SMA?
The results provided early evidence that targeting muscle alongside existing SMA treatments could potentially offer additional benefits for some people living with SMA.
However, there are important limitations.
TOPAZ was a small Phase 2 study involving 58 people, and the different groups within it were even smaller. It also wasn’t a large placebo-controlled Phase 3 trial, so the findings couldn’t by themselves establish how effective apitegromab is or who is most likely to benefit.
Instead, the findings provided evidence to support further research into apitegromab, including a larger Phase 3 clinical trial.
The study also only included people aged 2–21 with particular levels of motor function. This means we can’t assume that the findings would be the same for adults, people with different levels of SMA-related weakness, or the wider SMA community.
In short
The TOPAZ study provided encouraging early evidence that apitegromab may be able to improve motor function for some people with Type 2 and Type 3 SMA by targeting muscle in a different way from existing SMA treatments.
The strongest improvements in this study were seen in younger children who had already received Spinraza from a young age.
These findings were an important step in the development of apitegromab, but further, larger studies were needed to establish its benefits and safety more confidently.
Further Information
First Scientific publication on TOPAZ >
Second scientific publication on TOPAZ >
At the end of June 2023, Scholar Rock announced the latest data from this phase 2 study:
After 36 months of the TOPAZ trial, the combination therapy continued to have a favourable safety profile. In addition, the treatment was shown to provide sustained increases in motor function and lead to improvements in patient-reported outcomes, such as reduced fatigue and enhanced ability to perform daily activities.
Apitegromab was associated with an average 4.0 point improvement in the Hammersmith Functional Motor Scale – Expanded (HFMSE) and a 2.4 point gain in the Revised upper limb module (RULM). These improvements are relative to the baseline test scores achieved by participants at the start of the study, when they will have been receiving SMN-dependent therapies for at least 6 months.
At this stage, more than 90% of the patients remain enrolled in the study, which is due for completion in April 2024.
27th October:
Scholar Rock presented the latest data from this trial at the 3rd International Scientific Congress on SMA in Barcelona, Spain
After 24 months of treatment, new data indicated that quality of life either stabilised or continued to improve over the assessment period. This was determined by analysing the effects of SMA through testing abilities to perform daily activities, levels of fatigue, and muscle endurance.
Of the 55 people with SMA who completed the 24 month extension period of the trial, 54 plan to continue to the 36 month stage, when further data will be released.
Scholar Rock’s press release >
23rd June:
Extension data presented at the previous week’s Cure SMA Research & Clinical Care Meeting, supported sustained and continued motor function improvement for non-ambulatory people living with SMA Types 2 and 3 and receiving an SMN-enhancement therapy.
In the main treatment period, participants were dosed intravenously every four weeks with apitegromab alone or with nusinersen (Spinraza™), an approved SMN therapy. The trial enrolled 58 participants, both in Europe and the U.S.
The primary efficacy endpoints were mean change from baseline in motor function tests at 12 months for participants who are able to walk (Cohort 1) and mean change from baseline in motor function tests at 12 months for participants who are not able to walk (Cohorts 2 and 3). The trial also includes multiple 12-month extension periods designed to evaluate longer-term outcomes.
The Results
The results of the TOPAZ trial extension period evaluating outcomes after 24-months of treatment show:
- Substantial increase in motor function of participants with SMA Types 2 and 3 who are not able to walk (cohorts 2 & 3) and are receiving an SMN therapy (Spinraza™)
- Stabilisation of motor function scores in people living with SMA Type 3 who are able to walk (cohort 1) and are receiving an SMN therapy (Spinraza™)
- No serious safety risks over 24 months
The incidence and severity of adverse events were consistent with the underlying patient population and background therapy. The five most common treatment-emergent adverse events (TEAEs) were headache, fever, upper respiratory tract infection, cough, and nasopharyngitis (inflammation of the nasal passages and throat). No deaths or serious adverse reactions have been observed with apitegromab. A total of 14 serious TEAEs have been reported over the 24-month treatment period, all assessed by the respective trial investigator as unrelated to apitegromab.
Of the 55 patients who completed the 24-month TOPAZ extension period, 54 have opted to continue treatment in the 36-month extension period.
Conclusion
Underscoring the 12 month TOPAZ trial findings, the 24-month results provide long-term data and evidence that participants receiving apitegromab experienced sizable motor function gains. This continued increase in motor function support the transformative potential of apitegromab for people living with SMA.
8th April:
Scholar Rock announced key findings from the 12-month top-line analysis:
Cohort 1: 23 Individuals aged 5 to 21 with ambulatory SMA Type 3 were given 20 mg/kg of apitegromab every four weeks as a single therapy, or in conjunction with nusinersen:
- A mean change from baseline in motor function tests (Revised Hammersmith Scale (RHS)) of a 0.3-point decline was observed.
- The majority of patients across the cohort maintained or improved their motor function, as reflected by a >0-point change from baseline in RHS score and 22% of patients attained a >3-point increase from baseline.
- These results suggest a potential clinical effect in certain people in this population.
Cohort 2: 14 individuals aged 5 to 21 with Type 2 and non-ambulatory Type 3 who had started nusinersen treatment at the age of 5 years or older, were given 20 mg/kg of apitegromab every four weeks.
- A mean change from baseline in Hammersmith Functional Motor Scale Expanded (HFMSE) of a 0.6-point improvement was observed.
- The majority of patients (64%) attained a >1-point increase from baseline and 29% of patients attained a >3-point increase from baseline.
- These results support the potential durability of the improvements in motor function observed at the six-month interim analysis.
- A mean change from baseline in HFMSE of 7.1-point and 5.3-point improvements in the 20 mg/kg dose and the 2 mg/kg dose arms, respectively, were observed. Across the full cohort, 59% of patients attained a >5-point increase and 35% of patients attained a >10-point increase from baseline.
- These results demonstrate further improvements in motor function beyond what had been observed at the six-month interim analysis.
- A dose response continued to be observed based upon clinical efficacy (HFMSE improvements) and pharmacodynamics (target engagement).
Cohort 3: 17 children aged 2 years or older with SMA Type 2 who had started treatment with nusinersen before age 5 years were given two doses of apitegromab (20 mg/kg and 2 mg/kg) in conjunction with nusinersen:
- A mean change from baseline in HFMSE of 7.1-point and 5.3-point improvements in the 20 mg/kg dose and the 2 mg/kg dose arms, respectively, were observed.
- Across the full cohort, 59% of patients attained a >5-point increase and 35% of patients attained a >10-point increase from baseline.
- These results demonstrate further improvements in motor function beyond what had been observed at the six-month interim analysis.
- A dose response continued to be observed based upon clinical efficacy (HFMSE improvements) and pharmacodynamics (target engagement).
Safety: The five most frequently reported treatment-emergent adverse events were headache, pyrexia, upper respiratory tract infection, cough, and nasopharyngitis. As of these 12-month top-line results, no safety signals for apitegromab have been identified.
Based on these results, initiation of a phase 3 trial of apitegromab was expected by the end of 2021.
28th October:
58 individuals with SMA Types 2 and Type 3 were recruited in January 2020. The key findings from the 6-month interim analysis include:
Improvements in motor function, as measured by Hammersmith Scales, were observed in all three evaluated cohorts:
- Cohort 1 evaluated SRK-015 as a single therapy or in conjunction with nusinersen in individuals with ambulatory SMA Type 3.
- Cohort 2 evaluated SRK-015 in conjunction with nusinersen in individuals with Type 2 or non-ambulatory SMA Type 3.
- Cohort 3 evaluated SRK-015 in individuals with SMA Type 2 and had initiated treatment with nusinersen before 5 years of age.
No safety and tolerability concerns for SRK-015 were identified from this interim analysis.
Scholar Rock believes that these findings demonstrate the therapeutic potential of SRK-015 in SMA Types 2 and 3.
25th November:
Scholar Rock announced the preliminary pharmacokinetic and pharmacodynamic analysis of the TOPAZ trial. This included data from 29 patients across the three cohorts:
- Cohorts 1 & 2: Patients treated with 20 mg/kg of SRK-015
- Cohort 3: Patients randomised to either 20 mg/kg or 2 mg/kg
These patients had received one dose of SRK-015 and were evaluated for four weeks as of the data cut-off.
The preliminary results demonstrated:
- Presence of latent myostatin in patients with SMA, further supporting the relevance of this drug target in SMA
- Robust and dose-dependent engagement between SRK-015 and latent myostatin
- No clinically significant safety signals had been observed as of the data cut-off for this preliminary analysis.