Apitegromab: Side Effects
Known side effects, contraindications, and interactions
๐TL;DR
- โข5 known side effects documented
- โข5 mild, 0 moderate, 0 severe
- โข3 contraindications listed
Compare side effects across multiple peptides โ
Side Effects Severity Chart
Most frequently reported adverse event in both TOPAZ and SAPPHIRE trials. Rates were similar between apitegromab (26%) and placebo (28%) in SAPPHIRE, suggesting this is related to the underlying SMA disease and background therapy rather than apitegromab itself.
Reported in approximately 25% of apitegromab patients and 23% of placebo patients in SAPPHIRE. Consistent with the pediatric SMA population and not attributable to apitegromab.
Reported in 22% of apitegromab patients vs 30% of placebo patients in SAPPHIRE. Actually more frequent in the placebo group, indicating no causal relationship with apitegromab.
Reported in approximately 23% of apitegromab patients and 20% of placebo patients in SAPPHIRE. Consistent with respiratory vulnerability in SMA.
Reported in 23% of apitegromab patients vs 17% of placebo patients in SAPPHIRE. Mild difference may be related to IV infusion.
โContraindications
- โขApitegromab has not yet been approved for any indication. Formal contraindications have not been established. The following are theoretical considerations from clinical trial exclusion criteria.
- โขKnown hypersensitivity to apitegromab or its excipients (none observed in clinical trials to date).
- โขType 1 SMA patients were not studied in SAPPHIRE and safety in this population has not been established.
โ ๏ธDrug Interactions
- โขNusinersen (Spinraza) was used as background therapy in the majority of SAPPHIRE participants. The combination was well-tolerated with no new safety signals.
- โขRisdiplam (Evrysdi) was used as background therapy in some SAPPHIRE participants. The combination was well-tolerated.
- โขTirzepatide was used in combination with apitegromab in the EMBRAZE obesity trial. The combination was well-tolerated with no serious adverse events or discontinuations related to apitegromab.
- โขTheoretical interaction with other myostatin pathway modulators (e.g., trevogrumab, bimagrumab, follistatin gene therapy) given overlapping pathway targets.
Community-Reported Side Effects
See which side effects community members report most frequently.
Based on 20+ community reports
View community protocolsClinical Trial Safety Data#
Apitegromab has an exceptionally favorable safety profile across multiple clinical trials. In the pivotal Phase 3 SAPPHIRE trial, adverse event rates were comparable between apitegromab and placebo, and no patients discontinued treatment due to adverse events. This favorable profile has been consistent across Phase 1 (healthy adults), Phase 2 (TOPAZ, SMA), Phase 3 (SAPPHIRE, SMA), and Phase 2 (EMBRAZE, obesity).
Reported Side Effects#
SAPPHIRE Phase 3 (SMA, 12 months)#
| Adverse Event | Apitegromab (n=128) | Placebo (n=60) |
|---|---|---|
| Pyrexia | 26% | 28% |
| Nasopharyngitis | 25% | 23% |
| Cough | 23% | 20% |
| Vomiting | 23% | 17% |
| Upper respiratory infection | 22% | 30% |
| Headache | 21% | 20% |
The key observation is that adverse event rates were remarkably similar between apitegromab and placebo, indicating that most reported events are related to the underlying SMA disease and background therapy rather than apitegromab.
TOPAZ Phase 2 (SMA, 12 months)#
The five most frequently reported treatment-emergent adverse events:
| Adverse Event | Frequency |
|---|---|
| Headache | 24.1% |
| Pyrexia | 22.4% |
| Upper respiratory infection | 22.4% |
| Cough | 22.4% |
| Nasopharyngitis | 20.7% |
No deaths, serious adverse reactions, or anti-drug antibodies were reported.
Long-Term Safety (TOPAZ 36-48 Month Extension)#
| Adverse Event | Cumulative Frequency |
|---|---|
| Pyrexia | 48.6% |
| Nasopharyngitis | 45.7% |
| COVID-19 | 40.0% |
| Vomiting | 40.0% |
| Upper respiratory infection | 31.4% |
These cumulative rates over 36+ months reflect the ongoing vulnerability of SMA patients to respiratory infections and are consistent with the natural history of the disease.
EMBRAZE Phase 2 (Obesity, 24 weeks)#
In the obesity trial with tirzepatide:
- No serious adverse events related to apitegromab
- No discontinuations related to apitegromab
- No deaths
- Generally well-tolerated in combination with tirzepatide
Safety Highlights#
No Anti-Drug Antibodies#
Across all trials (Phase 1, TOPAZ, SAPPHIRE), no patients developed anti-drug antibodies to apitegromab. This is notable for a biologic therapy and reflects the fully human nature of the antibody.
No Treatment-Related Discontinuations#
In SAPPHIRE, no patients discontinued treatment due to adverse events -- an exceptionally favorable finding for a 12-month injectable therapy.
Placebo-Like Safety Profile#
The most striking aspect of apitegromab's safety data is the similarity between active treatment and placebo arms in SAPPHIRE. This suggests that selective targeting of promyostatin/latent myostatin may avoid the off-target effects associated with broader myostatin pathway blockade.
Theoretical Concerns#
Selective vs Broad Myostatin Blockade#
Apitegromab's upstream, selective approach theoretically reduces risks compared to other myostatin pathway modulators:
| Concern | Apitegromab Risk | Broader Inhibitors |
|---|---|---|
| Muscle spasms | Not reported as signal | Common with bimagrumab, trevogrumab |
| Off-target TGF-beta effects | Not expected (prodomain specificity) | Possible with receptor blockers |
| Activin A pathway effects | No binding | Bimagrumab blocks; garetosmab targets |
| Cardiac hypertrophy | Uncertain long-term | Theoretical for all myostatin inhibitors |
Overall Safety Assessment#
| Assessment Criterion | Rating | Basis |
|---|---|---|
| Short-term tolerability | Excellent | Comparable to placebo in SAPPHIRE |
| Long-term tolerability | Good | Up to 48 months in TOPAZ extension |
| Immunogenicity | Excellent | No ADAs across all trials |
| Discontinuation rate | Excellent | Zero treatment-related discontinuations |
| Serious adverse events | Favorable | No treatment-related SAEs |
| Combination safety (SMA) | Favorable | Safe with nusinersen and risdiplam |
| Combination safety (Obesity) | Favorable | Safe with tirzepatide (EMBRAZE) |
Related Reading#
Unlock full side effects analysis
Free access to detailed safety profiles and interaction guidance for all peptides.
150+ peptide profiles ยท 30+ comparisons ยท 18 research tools
Frequently Asked Questions About Apitegromab
Explore Further
Medical Disclaimer
This website is for educational and informational purposes only. The information provided is not intended to diagnose, treat, cure, or prevent any disease. Always consult with a qualified healthcare professional before using any peptide or supplement.