Evidence Grade C — Moderate human evidence. 12 published studies, 10 human. 4 registered clinical trials.
Medically reviewed by a licensed medical professional
ACE-031 is a fusion protein — not a peptide — that was developed to intercept the signals that limit muscle growth, intended as a treatment for Duchenne muscular dystrophy (DMD). It was discontinued after clinical trials revealed bleeding-related safety concerns caused by the drug inadvertently trapping signals important for blood vessel health.
ACE-031 is also known by these brand and alternate names:
12 published studies: 10 human, 1 animal, 1 in-vitro, 0 reviews
ACE-031 has no marketing authorisation. A Phase I trial in healthy women showed increased lean mass and decreased fat mass. A Phase II trial in DMD (24 patients) showed lean body mass increases but was discontinued due to bleeding-related safety concerns (epistaxis, telangiectasias, and gum bleeding), likely caused by inhibition of BMP-9/10 vascular signalling.
ACE-031 is a large fusion protein (~90 kDa), not a peptide. Its clinical development was halted. The non-selective ligand-trapping profile — capturing beneficial vascular signalling molecules alongside the intended muscle-growth targets — illustrates the challenge of targeting the TGF-beta superfamily. Acceleron subsequently developed more selective agents.
ACE-031 functions as a soluble decoy version of the activin type IIB receptor. It circulates in the bloodstream and captures myostatin, activin, and related signalling molecules before they can reach cell-surface receptors, preventing the 'stop growing' signals they normally deliver to muscle. However, it also captures BMP-9 and BMP-10, which regulate blood vessel formation — a non-selectivity that likely caused the bleeding side effects.
Research suggests a Phase I trial in healthy women showed meaningful increases in lean mass and decreases in fat mass, and a Phase II DMD trial (24 patients) showed lean body mass increases. However, nosebleeds, skin blood vessel changes, and gum bleeding emerged — likely caused by the drug capturing vascular signalling molecules (BMP-9/BMP-10) alongside its intended muscle targets. The safety profile was considered unmanageable, and the developer (Acceleron Pharma) pivoted to more selective agents, eventually developing luspatercept (Reblozyl), which received FDA approval for a different condition. ACE-031 illustrates the challenge of targeting the TGF-beta superfamily, where many related signals share the same receptors.
PeptideTrace tracks 4 registered clinical trials for ACE-031 sourced from ClinicalTrials.gov.
Extension Study of ACE-031 in Subjects With Duchenne Muscular Dystrophy
Study of ACE-031 in Subjects With Duchenne Muscular Dystrophy
A Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Study of ACE-031 in Healthy Postmenopausal Women
A Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Study of ACE-031 (ActRIIB-IgG1)in Healthy Postmenopausal Volunteers
ACE-031 (Ramatercept, ACVR2B-Fc) is a soluble activin receptor type IIB extracellular domain fused to human IgG1 Fc. It is a fusion protein, not a peptide, with a molecular weight of approximately 90 kDa (CAS 1169766-01-1, DrugBank DB15116). Developed by Acceleron Pharma, ACE-031 has a half-life of 10-15 days in humans. Development timeline: Phase 1 initiated September 2008, Phase 2 DMD trial initiated May 2010, FDA clinical hold placed February 2011, program permanently discontinued May 2013. Acceleron-Shire partnership was valued at $45M upfront plus up to $453M in milestones.
Research suggests ACE-031 functions as a soluble decoy receptor intercepting TGF-beta superfamily ligands before they activate endogenous cell-surface ActRIIB. It traps six key ligands: myostatin (GDF-8), activin A, activin B, GDF-11, BMP-9, and BMP-10, with an IC50 for blocking myostatin signaling of approximately 180 pM. The critical safety insight is that trapping BMP-9 and BMP-10, which signal through ALK1 in endothelial cells to maintain vascular homeostasis, caused the epistaxis and telangiectasia adverse effects that terminated the program. Luspatercept (ACE-536/Reblozyl) introduced a single L79D substitution to eliminate this vascular toxicity.
Phase 1 SAD study (Attie et al. 2013, N=48 postmenopausal women, double-blind RCT): at 3 mg/kg, total body lean mass increased 3.3% (p=0.03, DXA), thigh muscle volume increased 5.1% (p=0.03, MRI). Phase 2 DMD trial (Campbell et al. 2017, N=24, double-blind RCT): 5.2% lean body mass increase at 1 mg/kg (p=0.015 vs. baseline). Safety: epistaxis 25%, telangiectasias 21%, both attributed to BMP-9/BMP-10 inhibition disrupting endothelial vascular homeostasis. All events were reversible upon discontinuation. In wild-type mice, ACVR2B/Fc caused up to 60% increase in muscle mass in 2 weeks. WADA studies confirmed 12 of 14 black-market products contained ACVR2B-related proteins.
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Somatrogon is marketed as Ngenla (approved June 2023) for paediatric growth hormone deficiency in children aged 3 years and older. In the pivotal trial, once-weekly somatrogon produced growth rates equivalent to daily somatropin injections (10.1 cm/year versus 9.8 cm/year), confirming that reducing injection frequency does not compromise growth outcomes. Ngenla represents a meaningful advance for paediatric patients and their families, reducing injections from 365 to 52 per year. Treatment adherence has been a persistent challenge with daily growth hormone, and weekly dosing is expected to improve long-term outcomes through better compliance. Somatrogon competes directly with somapacitan (Sogroya), the other approved weekly growth hormone, creating a new generation of less burdensome treatment options.
Somapacitan is marketed as Sogroya (approved August 2020 for adult growth hormone deficiency; expanded April 2023 to paediatric growth hormone deficiency in children aged 2.5 years and older). It is the first once-weekly growth hormone approved for both adult and paediatric patients. In adults, clinical trials showed improvements in body composition including reduced truncal fat. In children, growth rates were comparable to daily somatropin. The albumin-binding approach provides predictable drug levels with lower peak-to-trough variation than some other long-acting growth hormone technologies. Sogroya competes with somatrogon (Ngenla) in the growing once-weekly growth hormone market, with both products expected to gradually replace daily injections as the standard of care.
PEG-MGF has no marketing authorisation. No peer-reviewed studies of PEG-MGF as a defined PEGylated peptide entity exist. The PEG chain length, attachment site, and resulting pharmacological properties are not standardised. The absence of any characterisation studies means that products sold as PEG-MGF through unregulated channels have no defined molecular identity, no quality standards, and no basis for predicting their behaviour. This compound represents one of the least-characterised entries in this database.
Evidence Reviews
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