ACE-031, given the international nonproprietary name ramatercept, is an experimental, injectable protein drug that works as a “decoy” receptor. It is built from the outer, ligand-binding part of the human activin type IIB receptor (ActRIIB), joined to the Fc tail of a human IgG1 antibody. Circulating in the blood, it soaks up myostatin and several related proteins that normally hold back muscle growth (Attie et al., Muscle Nerve 2013; Reichel et al., Drug Test Anal 2025). Acceleron Pharma developed it, with Shire as a partner from 2010, as a possible treatment for Duchenne muscular dystrophy (DMD).
The single most important fact about ACE-031 is that its development was stopped for safety reasons. A placebo-controlled trial in boys with DMD was halted in 2011 after nosebleeds and telangiectasias (small dilated blood vessels visible in the skin) appeared in treated boys. Acceleron and Shire abandoned the drug in 2013 (Campbell et al., Muscle Nerve 2017; Acceleron prospectus, 2013). It was never approved anywhere. Products sold online under the name ACE-031 have been tested by an anti-doping laboratory, and none of the 14 products examined actually contained ACE-031 (Reichel et al., Drug Test Anal 2025).
This page summarizes what the published trials, trial registries, Acceleron’s regulatory filings and anti-doping researchers report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| What it is | Recombinant fusion protein: extracellular domain of human ActRIIB joined to the Fc domain of human IgG1, forming a two-chain (homodimeric) molecule |
| Drug class | Activin receptor IIB “ligand trap” (soluble decoy receptor); myostatin/activin pathway inhibitor |
| Developer | Acceleron Pharma, partnered with Shire from September 2010 to June 2013 |
| Route studied | Subcutaneous injection |
| Doses studied in humans | Single doses of 0.02–3 mg/kg (healthy postmenopausal women); 0.5 mg/kg every 4 weeks or 1.0 mg/kg every 2 weeks (boys with DMD) |
| Half-life | Mean 10–15 days (≈240–360 h) after a single subcutaneous dose in healthy women |
| Main safety signal | Nosebleeds (epistaxis) and telangiectasias in the DMD trial |
| Approval status | Never approved; clinical hold in 2011; development discontinued in 2013 |
| US controlled-substance status | Not listed in the anabolic steroid schedule (21 CFR 1308.13) |
| WADA status | Named in class S4.3 as an example of a decoy activin receptor; prohibited at all times |
What it is
Myostatin (also called GDF8) is a protein made by muscle that limits how large muscles grow. It and several related members of the TGF-β family, such as activin A and GDF11, signal by docking onto activin type II receptors on the muscle cell surface, mainly ActRIIB. ACE-031 is a free-floating copy of the part of ActRIIB that grabs these ligands. Because the ligands bind the drug instead of the real receptor, the brake on muscle growth is released (Attie et al., Muscle Nerve 2013).
Structurally, the anti-doping analysis of ACE-031 describes it as a homodimeric protein of 343 amino acids with three sugar-attachment (N-glycosylation) sites. Each chain consists of an ActRIIB fragment, a short three-glycine linker and a human IgG1 Fc fragment. The Fc part pairs two chains together and slows the protein’s removal from the body (Reichel et al., Drug Test Anal 2025).
The idea came from mouse work. A 2005 study showed that a soluble ActRIIB receptor increased muscle mass by up to 60% in 2 weeks in wild-type mice. The effect was smaller, but still present, in mice that lacked myostatin entirely, which showed that other ligands besides myostatin also restrain muscle growth (Lee et al., PNAS 2005). That is the main difference between a receptor decoy like ACE-031 and a drug aimed at myostatin alone: it blocks a wider set of signals.
How ACE-031 differs from ACE-083
Acceleron’s later muscle drug, ACE-083, used the same goal but a different design, partly to avoid the whole-body effects seen with ACE-031.
| Feature | ACE-031 (ramatercept) | ACE-083 |
|---|---|---|
| Built from | ActRIIB receptor extracellular domain | Shortened follistatin, a natural myostatin-binding protein |
| Route | Subcutaneous, acts throughout the body | Injected into one muscle, designed to act locally |
| Human half-life | 10–15 days | Not measurable; little drug in blood after the first day |
| Outcome | DMD trial stopped for nosebleeds and telangiectasias; discontinued 2013 | Grew injected muscles but did not improve function; discontinued 2020 |
Sources: Attie et al., Muscle Nerve 2013; Campbell et al., Muscle Nerve 2017; Pearsall et al., Sci Rep 2019; Acceleron, March 2020. The ACE-083 page covers that drug’s trials in detail.
The BMP9 problem
ActRIIB does not only bind muscle-related ligands. Acceleron researchers later reported that the homodimeric ActRIIB-Fc design traps bone morphogenetic protein 9 (BMP9), which they describe as a vascular regulatory ligand, and that it affected blood-vessel outgrowth in a mouse retinal assay. They built a successor molecule (ActRIIB:ALK4-Fc) specifically so that it would not trap BMP9 (Li et al., J Clin Invest 2021). Former Acceleron scientists have since written that the vascular side effects of ACE-031 were attributed to inhibition of ligands beyond myostatin and activin A, particularly BMP9 (Cadena et al., PLoS One 2026). This explanation comes from the developer’s own researchers and from animal and laboratory work rather than from a human mechanistic study.
Pharmacokinetics
The only published human pharmacokinetic data come from the single-dose study in 48 healthy postmenopausal women (Attie et al., Muscle Nerve 2013):
| Parameter | Result |
|---|---|
| Doses | 0.02–3 mg/kg, one subcutaneous injection |
| Exposure (AUC and peak level) | Increased in proportion to dose |
| Mean elimination half-life | 10–15 days |
A half-life of 10–15 days is long, which is why the DMD trial dosed only every 2 or 4 weeks. It also means that once side effects appear, the drug stays in the body for weeks.
Development history and regulatory status
| Date | Event |
|---|---|
| Sept 2008 – Jul 2009 | Phase 1 single-dose study in 48 healthy postmenopausal women (NCT00755638) |
| Aug 2009 – Feb 2011 | Phase 1 multiple-dose study in 70 healthy postmenopausal women; completed, no results posted (NCT00952887) |
| Apr 2010 – Jun 2011 | Phase 2 trial in 24 boys with DMD; terminated based on preliminary safety data (NCT01099761) |
| Sept 8, 2010 | Acceleron and Shire sign a joint development deal for ACE-031; Shire pays $45.0 million up front |
| Oct 2010 – May 2011 | Open-label extension in 11 boys; terminated based on preliminary safety data (NCT01239758) |
| 2011 | Clinical development placed on clinical hold because of preliminary safety observations |
| April 2013 | Acceleron and Shire decide not to advance ACE-031; collaboration ends June 30, 2013 |
Acceleron’s 2013 IPO prospectus states that after gathering further information from animal toxicology studies, the two companies concluded that the risk-benefit profile of ACE-031 was not appropriate for the intended patients, boys aged four and older with a genetic muscle-wasting disease. The prospectus also states that Acceleron had no plans to continue development (Acceleron prospectus, 2013).
- No approval. ACE-031 never reached a marketing application in any country.
- Not a controlled substance in the US. It is a protein, not an anabolic steroid, and is not listed in Schedule III (21 CFR 1308.13).
- Named on the WADA list. Class S4.3 (“agents preventing activin receptor IIB activation”) lists “decoy activin receptors (e.g. ACE-031)”. S4.3 substances are prohibited in and out of competition and are non-Specified Substances (WADA 2026 Prohibited List). The same class covers the activin receptor antibody bimagrumab, the myostatin antibody apitegromab and follistatin (follistatin-344).
What the research shows
Only two human studies have been published: 48 healthy women and 24 boys with DMD. Neither studied athletes, healthy men or strength outcomes in healthy people.
Animal studies
- Mice. In 8-week-old mice treated for 28 days, ACE-031 raised body weight by 16% versus vehicle, and the weights of four leg muscles by 26–46%. Both slow (type I) and fast (type II) fibers grew, by 22% and 28% in cross-sectional area in the soleus (Cadena et al., J Appl Physiol 2010).
- Marmosets. In a small primate study, 8 marmosets received 3.0 mg/kg ACE-031 weekly for 14 weeks and 4 received vehicle. Lean body mass rose from baseline only in the treated animals. Biceps fiber cross-sectional area was 20% greater for type II and 34% greater for type I fibers, and an isolated leg muscle produced more absolute and specific force (Cadena et al., PLoS One 2026). The authors note that the small control group limited statistical power.
These are animal results; the human trials below are the only data on people.
Healthy postmenopausal women (phase 1, n = 48)
This double-blind study randomized healthy postmenopausal women 3:1 to one subcutaneous dose of ACE-031 (0.02–3 mg/kg) or placebo (Attie et al., Muscle Nerve 2013). At day 29, the 3 mg/kg group showed:
| Measure | Change at day 29, 3 mg/kg | p |
|---|---|---|
| Total body lean mass (DXA) | +3.3% | 0.03 |
| Thigh muscle volume (MRI) | +5.1% | 0.03 |
The authors also reported statistically significant changes in blood markers that they interpreted as improved bone and fat metabolism. A second, multiple-dose study in 70 healthy postmenopausal women was completed in 2011, but no results have been posted or published (NCT00952887).
Duchenne muscular dystrophy (phase 2, n = 24)
DMD is an inherited disease of boys in which muscle progressively breaks down because the protein dystrophin is missing. The trial enrolled walking boys aged 4 and older who had taken corticosteroids for at least a year. It was randomized, double-blind and placebo-controlled, with ascending doses. Each cohort was treated for 12 weeks and followed for another 12 weeks (Campbell et al., Muscle Nerve 2017; NCT01099761).
The planned third cohort (2.5 mg/kg every 4 weeks) never enrolled because the study was stopped after the second dose level. Results posted to the registry, at the end-of-study visit about 24 weeks after starting:
| Outcome | 0.5 mg/kg every 4 wk (n = 9) | 1.0 mg/kg every 2 wk (n = 9) | Placebo (n = 6) |
|---|---|---|---|
| Lean body mass, % change (mean ± SE) | +3.6 ± 1.3 | +4.1 ± 1.5 | +2.6 ± 1.8 |
| Lumbar spine bone density, % change (mean ± SE) | +1.6 ± 1.8 | +4.4 ± 1.5 | +0.3 ± 4.4 |
| 6-minute walk, change in m, boys aged 10 or older (mean ± SD) | +4.5 ± 37.6 | −3.2 ± 35.5 | −47.6 ± 34.5 |
| 6-minute walk, change in m, boys under 10 (mean ± SD) | +43.8 ± 61.5 | +2.5 ± 35.6 | +5.2 ± 23.6 |
| 10-meter walk/run time, change in s (mean ± SD) | +0.7 ± 0.9 | +0.7 ± 0.9 | +1.0 ± 0.8 |
The published paper describes these as trends: maintained 6-minute walk distance versus a decline on placebo, and more lean mass and bone density with less fat mass, none of which reached statistical significance (Campbell et al., Muscle Nerve 2017). The groups were very small, the registry does not report statistical comparisons, and growing boys gain lean mass on placebo too. Hand-held strength scores at the elbow and knee did not show a consistent advantage for ACE-031 (NCT01099761).
Side effects and risks
No product has a label. The data below come from the two published studies (48 healthy women and 24 boys with DMD, including placebo recipients), all treated under medical supervision.
Nosebleeds and telangiectasias
These vascular effects are why the drug was stopped. Adverse events in the DMD trial, as posted to the registry (NCT01099761):
| Adverse event | 0.5 mg/kg every 4 wk (n = 9) | 1.0 mg/kg every 2 wk (n = 9) | Placebo (n = 6) |
|---|---|---|---|
| Epistaxis (nosebleeds) | 1 | 5 | 0 |
| Telangiectasia | 0 | 5 | 0 |
| Injection-site erythema (redness) | 3 | 6 | 3 |
| Headache | 1 | 3 | 1 |
| Any drug-related adverse event | 1 | 6 | 0 |
| Serious adverse events | 0 | 0 | 0 |
The events clustered at the higher dose. The study authors state that none were serious or severe, but that these non-muscle effects contributed to the decision to discontinue (Campbell et al., Muscle Nerve 2017). The extension study was also terminated (NCT01239758), and Acceleron reported that animal toxicology data gathered afterward supported ending development (Acceleron prospectus, 2013).
The same pattern appears with an approved drug from the same family. Sotatercept (Winrevair), an activin receptor type IIA-Fc fusion protein approved for pulmonary arterial hypertension, lists epistaxis in 22.1% vs 1.9% and telangiectasia in 16.6% vs 4.4% of patients versus placebo in the STELLAR trial (Winrevair label). Sotatercept is a different molecule, but the comparison shows that blood-vessel effects are a recognized risk of activin receptor-based ligand traps.
Healthy volunteers
In the single-dose study, ACE-031 was described as generally well tolerated, with injection-site erythema among the reported adverse events (Attie et al., Muscle Nerve 2013). A single dose followed for a few weeks says little about repeated use.
What is unknown
- There are no data on use beyond 12 weeks of dosing, in healthy men, in athletes, or alongside other drugs.
- The multiple-dose study in healthy women and the animal toxicology studies that informed the decision to stop have not been published.
- No regulator has reviewed ACE-031’s long-term safety, and with a 10–15 day half-life, effects can persist well after the last dose.
Products sold as ACE-031
ACE-031 is not available as a medicine. Anti-doping researchers bought 14 products sold online as ACE-031, from suppliers in the UK, Europe, China and the USA, all labeled “for research purposes only” or “not for human consumption” (Reichel et al., Drug Test Anal 2025). They found:
- None contained ACE-031. No product contained an ActRIIB-Fc fusion protein.
- 12 contained the full-length activin IIB receptor instead, including its membrane-spanning and internal parts, with no Fc fragment. The products were very impure, with many other proteins, and the protein’s size suggested it was made in bacteria rather than in the mammalian cells used for clinical-grade biologics.
- The other 2 contained different substances: one follistatin and one ipamorelin.
The same laboratory showed that its existing blood test for luspatercept, another ActRIIB-Fc protein, also detects this black-market material. In rats given 10 mg/kg, it was detectable in blood for up to 48 hours but not at 7 days; the authors caution that the detection window in humans may differ. Whatever is sold under this name has no verifiable link to the protein tested in Acceleron’s trials, and its effects in people are unknown.
Key takeaways
- A decoy receptor for muscle-limiting signals. ACE-031 (ramatercept) is the ActRIIB extracellular domain fused to an IgG1 Fc tail. It traps myostatin and related ligands throughout the body and has a half-life of 10–15 days.
- Modest muscle gains in people. One dose of 3 mg/kg raised lean mass by 3.3% and thigh muscle volume by 5.1% at day 29 in healthy postmenopausal women; in boys with DMD, gains were non-significant trends.
- Stopped for vascular side effects. Nosebleeds and telangiectasias appeared in 5 of 9 boys at the higher dose, the DMD trial was halted in 2011, and the drug was abandoned in 2013. The developer’s scientists attribute this to trapping BMP9.
- Different from ACE-083. The sibling compound ACE-083 was a locally injected follistatin protein that also failed, but for lack of functional benefit rather than safety.
- Black-market ACE-031 is not ACE-031. All 14 online products tested lacked the real drug; most held an impure, bacterially made receptor protein.
- Banned in sport by name. WADA lists ACE-031 under S4.3, prohibited at all times.
Sources
- Attie KM, Borgstein NG, Yang Y, et al. A single ascending-dose study of muscle regulator ACE-031 in healthy volunteers. Muscle Nerve. 2013;47(3):416–423. PubMed.
- Campbell C, McMillan HJ, Mah JK, et al. Myostatin inhibitor ACE-031 treatment of ambulatory boys with Duchenne muscular dystrophy: results of a randomized, placebo-controlled clinical trial. Muscle Nerve. 2017;55(4):458–464. PubMed.
- Acceleron Pharma. A randomized, double-blind, placebo-controlled, multiple ascending-dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ACE-031 (ActRIIB-IgG1) in subjects with Duchenne muscular dystrophy. NCT01099761. ClinicalTrials.gov.
- Acceleron Pharma. An open-label extension study to evaluate the safety, tolerability, and pharmacodynamics of ACE-031 (ActRIIB-IgG1) in subjects with Duchenne muscular dystrophy. NCT01239758. ClinicalTrials.gov.
- Acceleron Pharma. A randomized, double-blind, placebo-controlled, single-dose, dose-escalation study to evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic effects of ACE-031 (ActRIIB-IgG1) in healthy, postmenopausal volunteers. NCT00755638. ClinicalTrials.gov.
- Acceleron Pharma. A randomized, double-blind, placebo-controlled, multiple-dose, dose-escalation study to evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic effects of ACE-031 (ActRIIB-IgG1) in healthy postmenopausal women. NCT00952887. ClinicalTrials.gov.
- Acceleron Pharma. Prospectus, Form 424(b)(4). September 19, 2013. SEC.
- Lee SJ, Reed LA, Davies MV, et al. Regulation of muscle growth by multiple ligands signaling through activin type II receptors. Proc Natl Acad Sci U S A. 2005;102(50):18117–18122. PubMed.
- Cadena SM, Tomkinson KN, Monnell TE, et al. Administration of a soluble activin type IIB receptor promotes skeletal muscle growth independent of fiber type. J Appl Physiol (1985). 2010;109(3):635–642. PubMed.
- Cadena SM, Bogdanovich S, Khurana TS, et al. ACE-031, a soluble activin type IIB receptor, increases muscle mass and strength in the common marmoset (Callithrix jacchus). PLoS One. 2026;21(2):e0342666. PubMed.
- Li J, Fredericks M, Cannell M, et al. ActRIIB:ALK4-Fc alleviates muscle dysfunction and comorbidities in murine models of neuromuscular disorders. J Clin Invest. 2021;131(4):e138634. PubMed.
- Reichel C, Filip T, Gmeiner G, Thevis M. Gel electrophoretic detection of black market ACE-031. Drug Test Anal. 2025;17(10):1934–1946. PubMed.
- Merck Sharp & Dohme LLC. Winrevair (sotatercept-csrk) for injection, prescribing information. DailyMed.
- Pearsall RS, Davies MV, Cannell M, et al. Follistatin-based ligand trap ACE-083 induces localized hypertrophy of skeletal muscle with functional improvement in models of neuromuscular disease. Sci Rep. 2019;9(1):11392. PubMed.
- Acceleron Pharma. Acceleron announces topline results from the Phase 2 trial of ACE-083 in patients with Charcot-Marie-Tooth disease. Form 8-K, Exhibit 99.1. March 9, 2020. SEC.
- World Anti-Doping Agency. Prohibited List 2026, class S4.3. WADA 2026 Prohibited List.
- Drug Enforcement Administration. Schedule III anabolic steroids. 21 CFR 1308.13. eCFR.