Apitegromab (SRK-015)
Apitegromab (SRK-015) is a monoclonal antibody that selectively binds the pro- and latent forms of myostatin, blocking its activation rather than the mature ligand. Developed for spinal muscular atrophy, it showed improvements in motor function in trials and represents the most clinically advanced selective myostatin inhibitor.
01 Overview
Apitegromab is mechanistically distinct from earlier anti-myostatin antibodies: it targets promyostatin and latent myostatin, the inactive precursors, preventing their proteolytic conversion to active myostatin. This precursor-targeting is intended to give greater selectivity and avoid cross-reactivity with related growth factors.
In Phase 2 and Phase 3 programmes for spinal muscular atrophy — used on top of standard SMN-directed therapies — apitegromab improved motor-function scores in patients. It is the furthest-developed selective myostatin inhibitor and has drawn interest as proof that the pathway can yield functional benefit in the right disease context.
02 Mechanism
A humanised monoclonal antibody that binds pro- and latent myostatin, blocking their activation into mature myostatin and thereby preserving muscle in the setting of SMN-related motor-neuron disease.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Trial dosing (SMA) | 10–20 mg/kg | IV | Given roughly every 4 weeks as an adjunct in SMA trials; not yet a marketed muscle drug. |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Improved motor functionSMA patients on background therapy improved motor-function scores versus expected trajectory. | Several points on motor scales | Clinical | |
| Increased muscle massSelective myostatin precursor blockade increases muscle in the treated population. | Modest | Clinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| HeadacheHeadache was among the more frequently reported adverse events. | Mild | Common | Clinical | |
| Upper respiratory infectionsCommon infections were reported, broadly balanced with control. | Mild | Common | Clinical |