Objective:

Supported by extensive non-clinical data and an established safety profile in patients with neuromuscular disease, RESILIENT (NCT05337553) will study taldefgropeb’s efficacy and safety as an adjunctive therapy with SMN upregulators in patients with SMA.

Background:

Spinal muscular atrophy (SMA), a rare, genetic neurodegenerative disorder, affects approximately 1 in 10,000 births. SMA is caused by insufficient production of survival motor neuron (SMN) protein, a molecule essential for motor neuron survival.  Patients with SMA experience motor neuron loss, and associated muscular atrophy. SMN upregulators have offered advances in care. However, despite their use, many patients with SMA continue to experience muscle weakness that impairs function and quality of life. Myostatin inhibitors have shown promise in increasing muscle mass and function when administered along with SMN upregulators in murine SMA models. Taldefgrobep alfa (BHV-2000) is a novel, fully human recombinant protein myostatin inhibitor specifically designed to bind myostatin and act as an activin 2b receptor antagonist. 

Design/Methods:

Phase 3 RESILIENT is a randomized, placebo-controlled trial with a 48-wk double-blind phase and 48-wk open-label extension. Participants with SMA (ages 4-21 yrs) will receive weekly weight-based subcutaneous injections of taldefgrobep (35 mg or 50 mg) vs matching placebo. Participants must have genetically confirmed 5q autosomal recessive SMA with SMN2 copy number and plan to remain on the same SMN upregulator regimen throughout the study. Patients previously treated with a myostatin inhibitor are excluded. RESILIENT is not restricted nor limited to patients based on ambulatory status or SMA classification. The primary outcome measure is change in the 32-item Motor Function Measure total score from baseline to Week 48.  

Results:

Study recruitment from 53 sites around the world, is now completed.

Conclusions:

This phase 3 study aims to investigate the efficacy and safety of taldefgropeb as an adjunctive treatment with SMN upregulators in particpants with SMA.