Abstract Details

Apitegromab is an investigational, fully human, monoclonal antibody that specifically binds to proforms of myostatin—promyostatin and latent myostatin—thereby inhibiting myostatin activation.  

In the Type 2 cohort initiating nusinersen before age 5 (>2 years, n=17) patients were randomized, double-blind, 1:1 to 2mg/kg or 20mg/kg apitegromab.  63% of patients on 20mg/kg in this cohort experienced >6-point gains in HFMSE with a mean improvement from baseline of +7.1-points in HFMSE on top of background therapy.  The magnitude of (1) increase in serum latent myostatin (2) increase in motor function scores, and (3) time to reach HFMSE motor function benefit correlated with higher dose.

In the second cohort, nonambulatory Type 2/3 patients 5-21 years (n=14) receiving 20mg/kg apitegromab, 64% obtained ≥1-point increases and 29% ≥3-point increases in HFMSE from baseline. In both nonambulatory cohorts, improvements in RULM were achieved.

In the ambulatory cohort the effect of 20mg/kg apitegromab (5-21 years, n=23) receiving chronic nusinersen or not was studied. Functional stabilization was maintained in both groups, but overall 39% obtained ≥1-point and 22% obtained ≥3-point increases from baseline in RHS.  Substantial correlations were observed between RHS scores and target engagement marker, serum latent myostatin. Overall, greater improvements in motor function inversely correlated with characteristics of advanced disease, i.e. presence of scoliosis and contractures. 

The incidence and severity of AEs were consistent with the underlying patient population and background therapy

Apitegromab has the potential to be the first muscle-directed therapy to address motor function impairment affecting patients with SMA.