Post hoc analyses from the Phase 3 SAPPHIRE study evaluating apitegromab in patients with nonambulatory type 2 or 3 spinal muscular atrophy

Topic:

Clinical Trials

Poster Number: 189 M

Author(s):

Laurent Servais, MD PhD, University of Oxford, Andreea Seferian, MD, Institut I-Motion, Hôpital Trousseau, 26 avenue du Dr Arnold Netter, Paris, France, Jena Krueger, MD, Helen DeVos Children’s Hospital, Corewell Health, Valeria Sansone, MD, The NeMO Clinical Center in Milan, Neurorehabilitation Unit, Milan, Italy, Eugenio M. Mercuri, MD, Pediatric Neurology Institute, Catholic University and Nemo Pediatrico, Rome, Italy, Thomas Brown, PhD, Scholar Rock, Inc., Crystal Watson, MS, Scholar Rock, Inc., Cambridge, MA, USA, Lian Lin, PhD, Scholar Rock, Inc., Cambridge, MA, USA, Mouhamed Gueye, PharmD, Scholar Rock, Inc., Thomas Crawford, MD, Johns Hopkins University School of Medicine

Background: Despite advances with SMA treatments, many patients still manifest muscle weakness. By targeting increased contractile protein mass, myostatin—a negative regulator of muscle growth—may complement the denervation atrophy of SMA. The Phase 3, SAPPHIRE study (NCT05156320) showed 12mo of apitegromab, an investigational, antimyostatin treatment, improved motor function outcomes for patients with SMA also receiving an approved treatment (nusinersen/risdiplam).

Objectives: Post hoc analyses were conducted for the SAPPHIRE population aged 2-21y to assess the impact of several baseline characteristics on HFMSE outcomes following apitegromab (10 mg/kg and 20 mg/kg) or placebo treatment (nusinersen/risdiplam alone). Outcomes are reported as least squares mean (LSM) difference (SE) in HFMSE change from baseline for apitegromab vs placebo.

Results: After 12mo, the greatest change was observed for patients with ≤2y of current SMA treatment, prior to SAPPHIRE: LSM difference (SE) of 2.9 (2.08), favoring apitegromab. LSM difference (SE) for patients with longer SMA treatment exposure (2-4y, 4-6y, and >6y) was 1.7 (1.93), 0.8 (0.87), and 1.9 (1.44), respectively. Patients receiving apitegromab ≤5y since symptom onset saw notable increases in HFMSE score, with an LSM difference (SE) of 2.1 (2.02). Change in HFMSE continued to favor apitegromab for patients treated 5-10y and >10y since symptom onset with respective LSM differences (SE) of 0.8 (0.81) and 1.7 (1.10). The benefit of apitegromab also appeared greater in patients with higher baseline motor function, as patients with HFMSE scores ≥31 achieved the greatest gains after 12mo of apitegromab treatment: LSM difference (SE) of 2.6 (1.08). Despite lower HFMSE scores (≤20 or 21-30), patients receiving apitegromab experienced meaningful functional gains: LSM difference (SE) of 0.8 (0.73) and 1.6 (1.93).

Conclusions: These data illustrate that apitegromab confers additional functional benefit, regardless of baseline status, with the greatest benefit observed in patients treated early after symptom onset, SMA treatment initiation, or with higher motor function.