Peptides Similar to Apitegromab
Compare Apitegromab with related peptides and alternatives
📌TL;DR
- •4 similar peptides identified
- •Trevogrumab (REGN1033): undefined
- •Bimagrumab (BYM338): undefined
Quick Comparison
| Peptide | Similarity | Key Differences |
|---|---|---|
| Apitegromab (current) | - | - |
| Trevogrumab (REGN1033) | ||
| Bimagrumab (BYM338) | ||
| Follistatin | ||
| Myostatin (GDF-8) |
Overview#
Apitegromab occupies a unique position among myostatin pathway modulators as the only clinical-stage inhibitor that selectively targets the upstream activation step. While several approaches to reducing myostatin signaling have been pursued, they differ fundamentally in their molecular targets, selectivity, and clinical indications.
Myostatin Pathway Inhibition Landscape#
| Molecule | Type | Target | Specificity | Route | Lead Indication |
|---|---|---|---|---|---|
| Apitegromab (SRK-015) | Human IgG4-lambda | Pro/latent myostatin | Myostatin only (prodomain) | IV | SMA (Phase 3) |
| Trevogrumab (REGN1033) | Human IgG4-kappa | All myostatin forms | Myostatin only (all forms) | SC | Obesity (Phase 2) |
| Bimagrumab (BYM338) | Human IgG1-lambda | ActRIIA/B receptor | Myostatin + activin A + GDF-11 | IV | Obesity (Phase 2) |
| Domagrozumab (PF-06252616) | Humanized IgG1 | Active myostatin | Myostatin mature dimer | IV | DMD (discontinued) |
| Follistatin | Natural glycoprotein | Myostatin + activin A | Broad ligand trap | Gene therapy | Muscular dystrophy |
| Garetosmab (REGN2477) | Human mAb | Activin A | Activin A only | IV | FOP / obesity combo |
Detailed Comparisons#
Apitegromab vs Trevogrumab#
These two antibodies represent different strategies for myostatin-selective inhibition:
| Feature | Apitegromab | Trevogrumab |
|---|---|---|
| Developer | Scholar Rock / Novo Nordisk | Regeneron |
| Myostatin forms bound | Pro and latent only | All forms (mature, latent, precursor) |
| GDF-11 cross-reactivity | None | None |
| Activin A cross-reactivity | None | None |
| Administration | IV infusion Q4W | SC injection Q4W |
| SMA data | Phase 3 (SAPPHIRE, positive) | None |
| Obesity data | Phase 2 (EMBRAZE, positive) | Phase 2 (COURAGE, positive) |
| Lean mass preservation | 54.9% with tirzepatide | ~50% with semaglutide |
| GLP-1 partner | Tirzepatide | Semaglutide |
A key practical distinction is route of administration: trevogrumab's subcutaneous injection is more feasible for chronic obesity treatment than apitegromab's IV infusion. Scholar Rock has acknowledged this by developing SRK-439, a next-generation inhibitor potentially with SC formulation for the obesity market.
Apitegromab vs Bimagrumab#
These represent fundamentally different approaches to the pathway:
| Feature | Apitegromab | Bimagrumab |
|---|---|---|
| Target level | Ligand (prodomain) | Receptor (ActRIIA/B) |
| Pathways affected | Myostatin only | Myostatin + activin A + GDF-11 + others |
| Muscle spasms | Not reported | Common (10-15%) |
| Diarrhea | Not different from placebo | Common (~10%) |
| Body composition effect | Lean mass preservation | Lean mass gain + fat loss |
| Antibody subclass | IgG4 (no effector function) | IgG1 (effector function) |
| Immunogenicity | No ADAs detected | Low ADA rates |
Bimagrumab's broader blockade produces more dramatic body composition changes (simultaneous fat loss and lean mass gain) but at the cost of more side effects. Apitegromab's narrower approach may be better tolerated but shows more modest effects.
Apitegromab vs Follistatin#
| Feature | Apitegromab | Follistatin |
|---|---|---|
| Type | Monoclonal antibody (~150 kDa) | Natural glycoprotein (~35 kDa) |
| Specificity | Myostatin prodomain only | Myostatin + activin A + others |
| Administration | IV infusion | Gene therapy or research peptide |
| Clinical stage | Phase 3 (SMA) | Phase 1/2 (gene therapy in DMD/IBM) |
| Availability | Clinical trials only | Gene therapy trials or research suppliers |
| Half-life | 24-31 days | Minutes (native protein) |
Follistatin is the body's natural counterbalance to myostatin signaling but has a very short half-life, making it impractical as a therapeutic protein. Gene therapy approaches (AAV-FS344) aim to provide sustained follistatin expression.
Apitegromab vs Domagrozumab#
Domagrozumab (PF-06252616) was Pfizer's anti-myostatin antibody that targeted the active mature dimer -- the opposite end of the activation pathway from apitegromab. The SAPPHIRE trial for Duchenne muscular dystrophy was terminated in 2018 for lack of efficacy, raising questions about whether neutralizing only the active form is sufficient. Apitegromab's success in SMA suggests that upstream blockade (preventing activation) may be more effective than downstream neutralization.
Indication-Specific Comparisons#
Neuromuscular Disease (SMA/DMD)#
Only apitegromab has demonstrated clinical efficacy in a neuromuscular indication:
| Molecule | Indication | Phase | Outcome |
|---|---|---|---|
| Apitegromab | SMA Types 2/3 | Phase 3 | Positive (HFMSE +1.8, p=0.019) |
| Domagrozumab | DMD | Phase 2 | Failed (terminated 2018) |
| Bimagrumab | SIBM | Phase 2/3 | Failed (RESILIENT, no efficacy) |
| Follistatin gene therapy | DMD/IBM | Phase 1/2 | Mixed results |
Obesity / Body Composition#
Multiple myostatin pathway modulators are being tested as adjuncts to GLP-1 receptor agonists:
| Molecule | GLP-1 Partner | Lean Mass Effect | Phase | Status |
|---|---|---|---|---|
| Apitegromab | Tirzepatide | 54.9% preserved | Phase 2 | Positive (EMBRAZE) |
| Trevogrumab | Semaglutide | ~50% preserved | Phase 2 | Positive (COURAGE) |
| Bimagrumab | Semaglutide | Increased lean mass | Phase 2 | Ongoing (BELIEVE) |
| Garetosmab + Trevogrumab | Semaglutide | Greatest preservation | Phase 2 | Positive (COURAGE triplet) |
Key Differentiators#
Apitegromab's main differentiators from other myostatin modulators:
- Upstream mechanism: Only clinical-stage inhibitor targeting myostatin activation rather than the active form or receptor
- Placebo-like safety: AE rates comparable to placebo in SAPPHIRE -- better tolerated than bimagrumab or the trevogrumab triplet
- SMA validation: Only myostatin pathway modulator with positive Phase 3 data in a neuromuscular disease
- No immunogenicity: Zero anti-drug antibodies across all trials
- IV limitation: Unlike trevogrumab (SC), requires IV infusion -- a practical disadvantage for chronic treatment
Related Reading#
Frequently Asked Questions About Apitegromab
Explore Further
Disclaimer: For educational purposes only. Not medical advice. Read full disclaimer