ACE-031

What ACE-031 is

ACE-031, also called ramatercept, is a lab-made fusion protein. One end is the outer part of activin receptor type IIB (ActRIIB), the section that catches signaling proteins. The other end is the Fc tail of a human IgG1 antibody, which keeps the molecule circulating longer. It's a large protein rather than a short peptide, although online shops often list it alongside peptides.

Acceleron Pharma developed it, with Shire as its partner. Myostatin and related proteins in the same family normally limit muscle growth by binding ActRIIB on muscle cells. A soluble copy of the receptor acts as a decoy that soaks those proteins up before they reach the muscle. Our ACE-031 mechanism of action page covers the signaling in detail.

That design is also its weak point. ActRIIB binds more than myostatin, so a decoy built from it catches a wider set of proteins than a myostatin-only drug would. The 2017 trial report describes ACE-031 as binding "myostatin and related ligands," and the side effects that ended the program had nothing to do with muscle.

The healthy-volunteer study

The first human study, published in Muscle & Nerve in 2013, gave a single dose to 48 healthy postmenopausal women. Participants were randomized 3:1 to one subcutaneous injection of ACE-031 or placebo, with trial doses ranging from 0.02 to 3 mg/kg.

The authors reported that ACE-031 was generally well tolerated, with redness at the injection site among the adverse events. Its half-life was long, about 10-15 days. In the 3 mg/kg group, total lean mass measured by DXA rose 3.3% and thigh muscle volume measured by MRI rose 5.1% at day 29. Blood markers also hinted at effects on bone and fat metabolism.

So one dose changed muscle size in people. That's a meaningful signal, but it came from a small group of older women followed for weeks. It couldn't show whether the extra tissue meant more strength, and a single dose can't reveal longer-term safety problems. According to a 2011 statement from the two companies, some healthy adults in the early trials also had the minor bleeding and blood-vessel changes that later showed up in boys.

The Duchenne trial and why it stopped

The Phase 2 study (NCT01099761, study A031-03) began in April 2010 and enrolled 24 ambulatory boys with Duchenne muscular dystrophy at sites in Canada. It was a double-blind, placebo-controlled trial with safety as the primary goal. According to the trial registry, the two dose groups received 0.5 mg/kg every 4 weeks or 1.0 mg/kg every 2 weeks by subcutaneous injection for 12 weeks.

The trial stopped after the second dose group. In April 2011 the companies said they had terminated the study and suspended its extension (NCT01239758, 11 boys) after reviewing the safety data with the FDA and Health Canada. The concern was nosebleeds and gum bleeding, along with telangiectasias: small dilated blood vessels in the skin. The companies called these events minor and said they resolved once treatment stopped. The 2017 trial report also found no serious or severe adverse events. Still, unexplained bleeding from a drug meant for children with a lifelong disease wasn't something regulators or the sponsors were willing to accept without an explanation.

The efficacy results were trends, not findings. Boys on ACE-031 held roughly steady on the 6-minute walk test while the placebo group declined, but the gap wasn't statistically significant. Lean mass and bone density trended up and fat mass trended down. With 24 boys and a short treatment period, the study wasn't built to prove benefit. The numbers by group are on our ACE-031 clinical trial results page.

Why development ended

The studies stayed on hold from February 2011. On May 2, 2013, the two companies announced they had ended their collaboration on ACE-031 and related molecules and would not restart the program. In a letter quoted by the Muscular Dystrophy Association, the companies said additional nonclinical and toxicology studies run after the hold "do not support further development." We found no public account of what those animal studies showed.

As of October 2026, no company is developing ACE-031. Both study records on ClinicalTrials.gov remain marked as terminated, and the sponsor is now listed as Acceleron, a subsidiary of Merck.

Why it matters for later drugs

ACE-031 showed that blocking this pathway builds muscle in humans, and also that a broad decoy brings effects outside muscle. Later programs mostly moved to antibodies that target one protein or one receptor family.

• Apitegromab (Isembyld) is an antibody that WADA groups with myostatin- or precursor-neutralizing antibodies. In September 2026 the FDA approved it for spinal muscular atrophy (SMA) in patients aged 2 and older who already take an SMN2-targeted treatment. As of October 2026 it's the first approved drug aimed at the myostatin pathway. It's approved for SMA, not for building muscle, and the FDA notes an increased risk of fractures.
• Bimagrumab is an antibody against activin type II receptors. In the Phase 2 BELIEVE trial of 507 adults with obesity (Nature Medicine, 2026), combination groups lost 0.8% to 2.3% of lean mass at 48 weeks when it was added to semaglutide, versus 4.7% to 6.9% on semaglutide alone.
• Trevogrumab is a myostatin antibody from Regeneron. In the Phase 2 COURAGE trial, reported at the EASD meeting in October 2026, it reduced lean-mass loss on semaglutide but didn't add weight loss. A separate arm that combined higher-dose trevogrumab with the activin A antibody garetosmab had a high rate of side effects and two deaths, and Regeneron dropped that combination.

Blocking this pathway reliably shifts body composition in people. Whether it improves strength or function is less clear outside SMA, where apitegromab's approval rests on a motor-function scale. The garetosmab result echoes ACE-031: hitting more of the pathway at once tends to bring more side effects. Our comparison of myostatin inhibitors and anabolic steroids puts these numbers in context, and the myostatin inhibitors overview covers the wider class.

Status in sport

WADA's 2026 Prohibited List names ACE-031 under S4.3, agents preventing activin receptor IIB activation, as its example of a decoy activin receptor. Substances in S4.3 are prohibited at all times (in and out of competition). The same section also names bimagrumab and apitegromab, along with follistatin. A 2025 paper in Drug Testing and Analysis adapted an existing test for luspatercept, another ActRIIB-Fc fusion protein, to detect black-market ACE-031 products, and showed detection in rat serum.

What online 'ACE-031' vials contain

The real drug hasn't been made since the program ended in 2013, so vials labeled ACE-031 on research-chemical sites come from unknown manufacturers. There are no human data on these products.

That 2025 study, by anti-doping researchers, tested 14 black-market ACE-031 products. Two contained no protein that reacted with ActRIIB antibodies. The other 12 contained full-length human activin receptor IIB instead of ACE-031, with no Fc fusion, mixed with many other proteins. None of the products tested was the molecule used in the clinical trials.

This matters for reading user reports. Whatever people describe after injecting these vials reflects whatever was in the vial rather than ACE-031. None of it carries over from the trial data above. Vials sold as follistatin raise similar identity questions.

What we still don't know

• What the post-2011 animal toxicology studies found. As far as we could tell, the details were never published.
• Which ligand, if any single one, caused the bleeding and blood-vessel changes. The trial report calls them non-muscle adverse events without naming a cause.
• Whether the more selective drugs avoid these effects over years of use. The obesity trials so far run about one to one and a half years.