Apitegromab

ID: apitegromab

Aliases: SRK-015, anti-promyostatin antibody, latent myostatin antibody

Type: compound

Route/form: intravenous infusion every 4 weeks in EMBRAZE and SMA studies

Status: investigational_bla_under_review_for_sma

Evidence level: early human

Best data tier: early human + human controlled/review

Support scope: human, non-human/mechanistic, context

Source types: clinical_trial_registry, company, company_regulatory, early_human, human_rct, human_trial, structural

Linked sources: 9

Broad outcomes: Fat loss / metabolic health, Muscle growth / performance / recovery, PEDs / AAS / thermogenics

Reading note: These are curation notes anchored to linked sources, not a clinical recommendation or protocol.

Targets / mechanism

• pro-myostatin and latent myostatin binding
• selective inhibition of myostatin activation
• tirzepatide-associated lean-mass preservation signal

Optimization domains

• metabolic
• obesity
• body composition
• muscle
• sarcopenia
• myostatin
• GLP-1 adjunct
• fat loss
• SMA

Research basis

• EMBRAZE sponsor-reported phase 2 obesity data say IV apitegromab plus tirzepatide preserved more lean mass than tirzepatide alone while keeping fat loss similar, shifting loss composition from roughly 70% fat to 85% fat.
• Human phase 1 data show IV apitegromab engages latent myostatin with dose-dependent pharmacodynamics, and SMA studies provide longer human exposure and functional-context evidence.
• Mechanistically it is narrower than broad ActRII blockade: it targets pro/latent myostatin activation and is designed to avoid activin A, GDF11, BMP9/10, and TGF-beta1 cross-reactivity.

Limits, risks, and missing evidence

• The obesity-specific EMBRAZE findings are sponsor-reported topline data at this curation point, not yet a peer-reviewed obesity paper.
• SMA motor-function data do not directly prove performance, hypertrophy, or metabolic benefit in otherwise healthy users losing weight.
• It is an IV monoclonal antibody with regulatory review focused on SMA, not an approved obesity or performance drug.

Risk flags

• investigational
• BLA under review for SMA
• monoclonal antibody
• IV infusion
• sponsor reported obesity data
• lean mass not function
• medical supervision
• doping

Linked papers, labels, and reviews

1. Scholar Rock Reports Positive Phase 2 EMBRAZE Trial Results Demonstrating Statistically Significant Preservation of Lean Mass with Apitegromab During Tirzepatide-Induced Weight Loss
   company / businesswire_apitegromab_embraze_2025
   Sponsor-reported 24-week EMBRAZE phase 2 obesity results: apitegromab plus tirzepatide preserved more lean mass and shifted loss composition toward fat; not a peer-reviewed obesity paper at this curation point.
2. EMBRAZE: Efficacy and Safety of Apitegromab for the Treatment of Adults Who Are Overweight or Obese
   clinical_trial_registry / clinicaltrials_embraze_apitegromab_tirzepatide
   ClinicalTrials.gov registry for EMBRAZE; completed phase 2 study with IV apitegromab every 4 weeks plus weekly SC tirzepatide.
3. A Randomized Phase 1 Safety, Pharmacokinetic and Pharmacodynamic Study of the Novel Myostatin Inhibitor Apitegromab (SRK-015): A Potential Treatment for Spinal Muscular Atrophy
   early_human / springer_apitegromab_phase1_2021
   Randomized placebo-controlled phase 1 study in healthy adults; IV apitegromab showed dose-dependent latent-myostatin target engagement and tolerability up to 30 mg/kg.
4. Long-term efficacy, safety, and patient-reported outcomes of apitegromab in patients with spinal muscular atrophy: results from the 36-month TOPAZ study
   human_trial / frontiers_apitegromab_topaz_36mo_2024
   Open-label extension in SMA, not obesity; useful for longer human exposure and function/safety context around selective pro/latent-myostatin inhibition.
5. Structural basis of specific inhibition of extracellular activation of pro- or latent myostatin by the monoclonal antibody SRK-015
   structural / pubmed_apitegromab_srk015_structure_2020
   Biochemical/structural mechanism source explaining how SRK-015/apitegromab binds pro- and latent myostatin and prevents activation rather than broadly blocking ActRII ligands.
6. Scholar Rock Reports First Quarter 2026 Financial Results and Recent Business Highlights
   company_regulatory / scholarrock_apitegromab_bla_accepted_2026
   Current regulatory context as of May 2026: FDA accepted the apitegromab BLA for SMA with a September 30, 2026 PDUFA date; this does not mean obesity approval.
7. A Randomized Phase 1 Safety, Pharmacokinetic and Pharmacodynamic Study of the Novel Myostatin Inhibitor Apitegromab (SRK-015): A Potential Treatment for Spinal Muscular Atrophy
   human_rct / pubmed_apitegromab_phase1_2021
   Randomized phase 1 apitegromab/SRK-015 study in healthy adults; supports IV exposure, latent-myostatin target engagement, PK/PD, safety, and immunogenicity context.
8. Safety and Efficacy of Apitegromab in Patients With Spinal Muscular Atrophy Types 2 and 3: The Phase 2 TOPAZ Study
   human_rct / pubmed_apitegromab_topaz_2024
   Phase 2 TOPAZ SMA study; adds disease-context human safety/function evidence for latent-myostatin inhibition.
9. Safety and efficacy of apitegromab in nonambulatory type 2 or type 3 spinal muscular atrophy (SAPPHIRE): a phase 3, double-blind, randomised, placebo-controlled trial
   human_rct / pubmed_apitegromab_sapphire_2026
   Phase 3 SAPPHIRE SMA trial; useful for longer clinical-development evidence, but disease context is not obesity or healthy performance.