MDA 2026: Apitegromab may boost motor function for people with SMA
SAPPHIRE trial analysis finds stronger benefits in patients treated earlier
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- Apitegromab, an add-on therapy for SMA, improves motor function by strengthening muscles.
- Early initiation of apitegromab treatment leads to greater motor function benefits in SMA patients.
- This therapy is for non-ambulatory SMA types 2/3; FDA approval is anticipated.
Apitegromab, a muscle-strengthening therapy for spinal muscular atrophy (SMA), helped improve motor function in a new analysis of Phase 3 trial data, with the greatest gains seen in people who started treatment earlier.
In the Phase 3 SAPPHIRE study (NCT05156320), participants received apitegromab in addition to disease-modifying treatments for SMA. “These data illustrate that apitegromab confers additional functional benefit … with the greatest benefit observed in patients treated early after symptom onset, SMA treatment initiation, or with higher motor function,” the researchers wrote.
The findings were presented at the Muscular Dystrophy Association (MDA) Clinical & Scientific Conference 2026 in Orlando, Florida, in a poster titled, “Post hoc analyses from the Phase 3 SAPPHIRE study evaluating apitegromab in patients with nonambulatory type 2 or 3 spinal muscular atrophy.” Several co-authors are employees of Scholar Rock, the company developing apitegromab.
Scholar Rock preparing new FDA submission for apitegromab
Scholar Rock plans to resubmit an application to the U.S. Food and Drug Administration (FDA) seeking approval of apitegromab. The agency declined to approve an earlier application last year due to manufacturing issues. The company says it has taken steps to address those concerns. If apitegromab is approved, Scholar Rock has said it hopes to make the therapy available in the U.S. by the end of this year.
SMA is caused by genetic mutations that reduce levels of the survival motor neuron (SMN) protein. SMN helps maintain the nerve cells that control movement. Without enough of this protein, these nerve cells gradually die, leading to characteristic symptoms of muscle weakness and wasting.
Disease-modifying treatments for SMA, including Spinraza (nusinersen) and Evrysdi (risdiplam), work by increasing SMN levels to slow or halt disease progression. However, “despite advances with SMA treatments, many patients still manifest muscle weakness,” the researchers wrote.
Apitegromab works by targeting myostatin, a protein that limits muscle growth. Researchers believe that blocking myostatin may help muscles grow stronger. The therapy was designed to be used alongside SMN-targeting treatments.
Phase 3 SAPPHIRE trial evaluated apitegromab in nonambulatory SMA
The Phase 3 SAPPHIRE trial tested apitegromab in nonambulatory participants ages 2 to 21 with SMA type 2 or type 3. SMA type 2 usually begins between 6 and 18 months of age, while type 3 starts after 18 months but before adulthood. All participants could sit independently but were unable to walk and were already receiving Spinraza or Evrysdi.
A total of 188 participants received either a placebo or apitegromab at doses of 10 mg/kg or 20 mg/kg. The treatment was given as intravenous, or into-the-vein, infusions every four weeks for up to one year.
On average, participants receiving apitegromab showed improvements on the Hammersmith Functional Motor Scale-Expanded (HFMSE), a standard measure of motor function. In contrast, the placebo group had significantly poorer outcomes, with a decline in HFMSE score. Overall, apitegromab-treated participants scored an average of 1.8 points higher than those receiving placebo on the HFMSE.
For this post hoc analysis, researchers examined which groups of participants experienced the greatest benefit from apitegromab. Participants were categorized by age, time since symptom onset, length of SMN-targeting treatment, and motor function at the start of the study. Although improvements were seen overall, some groups experienced larger gains than others.
Younger participants and earlier treatment linked to larger gains
Among younger participants at the start of the study, HFMSE scores improved more in those receiving apitegromab than in those receiving placebo on top of SMN-targeting therapy. Older participants generally showed smaller gains or stabilization in motor function in the apitegromab groups, while functional scores tended to decline in the placebo groups.
Participants who began treatment with apitegromab within five years of first experiencing SMA symptoms saw an average 2.1-point increase in HFMSE score compared with placebo. Those starting apitegromab between five and 10 years or more than 10 years after symptom onset had smaller relative gains, averaging 0.8 points and 1.7 points, respectively.
Likewise, individuals who had been on their current SMA treatment for no more than two years before joining SAPPHIRE had a stronger response than those with longer treatment exposure. The average HFMSE score difference compared with placebo was 2.9 points in participants with up to two years of prior treatment exposure, versus differences of up to 1.9 points in other groups.
Higher baseline motor function tied to stronger treatment response
Apitegromab also appeared to have a greater impact on motor function in participants who started the trial with higher HFMSE scores, corresponding with greater baseline abilities.
The researchers noted that the relatively small number of participants in each subgroup was a limitation of the analysis. However, taken together, the results suggest that starting apitegromab therapy earlier after symptom onset or treatment initiation may provide greater functional benefit.
“These insights may help set treatment expectations for patients with SMA and their caregivers,” the team concluded.
Note: The SMA News Today team is providing live coverage of the 2026 MDA Clinical & Scientific Conference March 8-11 in Orlando, Florida. Go here to see the latest stories from the conference.
