Follistatin and myostatin blockers: from ACE-031's trial halt to apitegromab

The brake on muscle

Myostatin, also called growth differentiation factor 8, is a protein that tells muscle to stop growing. Animals that lack it, through natural mutations or genetic engineering, develop extraordinary muscle mass, which is why blocking it has been a goal for treating muscle-wasting diseases since the late 1990s. Myostatin belongs to a family of related signalling proteins, including activins and bone morphogenetic proteins (BMPs), and that family resemblance turned out to be the central problem: a drug that blocks myostatin broadly may block its relatives too, and some of them do essential jobs elsewhere in the body.

Follistatin is the body's own binder of myostatin and activins. Sellers market it, and drug developers tried several other routes: decoy receptors that soak up myostatin and its relatives, antibodies against myostatin itself, antibodies against its receptors, and antibodies that stop myostatin being activated in the first place.

Two decades of programmes

From our encyclopedia and the trials cited below, as of October 3, 2026:

ACE-031: the trial that was stopped

ACE-031, from Acceleron, was a fusion of the activin receptor type IIB with an antibody fragment, a decoy that binds myostatin and related ligands. It was given every two to four weeks under the skin to boys with Duchenne muscular dystrophy in a randomised, double-blind, placebo-controlled ascending-dose trial. There were no serious or severe adverse events, but the study was stopped after the second dose level because of potential safety concerns: nosebleeds and telangiectasias, small dilated blood vessels ¹. Development was suspended in 2013; our entry attributes those effects to off-target blocking of BMP9 and BMP10, which are critical for blood vessel integrity ².

The efficacy signals were tantalising but not conclusive: a trend towards maintained six-minute walk distance against decline on placebo, and trends towards more lean mass, more bone density and less fat, none statistically significant ¹. The lesson shaped everything that followed: the broader the block, the more likely an effect outside muscle.

The antibodies that followed, and failed

Antibodies aimed squarely at myostatin were the obvious next step, because they should spare its vascular relatives. Domagrozumab was tested in 120 ambulatory boys with Duchenne over 48 weeks. It was generally safe, and muscle volume rose slightly but not significantly, yet the primary measure, time to climb four stairs, did not differ from placebo, and no secondary clinical measure improved ³.

In cancer cachexia, the wasting that accompanies advanced cancer, the antimyostatin antibody LY2495655 was tested with chemotherapy in 125 people with pancreatic cancer. The higher dose was stopped in 2014 because of an imbalance in deaths, the lower dose in 2015 for futility, and neither improved survival; the hazard ratio for death was 1.70 at the higher dose against placebo ⁴. Building muscle in a body that is wasting for other reasons proved much harder than in a healthy mouse.

Bimagrumab: muscle while losing fat

Bimagrumab blocks type II activin receptors, the receptors myostatin and activins signal through. In older adults with sarcopenia, thigh muscle volume rose 5% to 8% above baseline over 16 weeks, and slower walkers improved their gait speed and six-minute walk ⁵. But in inclusion body myositis, a muscle disease, the largest randomised trial found no improvement in six-minute walk over 52 weeks ⁶.

Its new direction is obesity. In adults with obesity and type 2 diabetes, 48 weeks of infusions cut fat mass sharply while lean mass rose 3.6% against a 0.8% fall on placebo, with body weight down 6.5% ⁷. Because GLP-1 drugs cause loss of lean tissue along with fat, bimagrumab has been tested alongside semaglutide. In a phase 2 trial of 507 adults with obesity, weight at 48 weeks fell 9.3 kg on high-dose bimagrumab, 14.2 kg on semaglutide 2.4 mg and 17.8 kg on the combination, against 3.3 kg on placebo, with continued improvement to week 72; muscle spasms, diarrhoea and acne were common with bimagrumab ⁸. Whether keeping lean mass translates into better strength, function or health over years is the question the next trials must answer. Our GLP-1 transition hub covers the approved weight-loss drugs.

Apitegromab: the first approval

Apitegromab, from Scholar Rock, took a narrower route: it binds the inactive precursor form of myostatin and stops it being activated, leaving mature myostatin's relatives alone. Early studies showed dose-dependent, sustained rises in serum latent myostatin, a sign the drug was engaging its target, without clinically meaningful safety changes ⁹. In the phase 2 trial in later-onset spinal muscular atrophy (SMA), motor function improved and the commonest side effect was headache ¹⁰.

The phase 3 SAPPHIRE trial, in nonambulatory people with type 2 or 3 SMA already receiving SMN-targeted therapy, met its primary endpoint for the combined 20 and 10 mg/kg groups, though 20 mg/kg alone did not separate significantly from placebo; no patient stopped because of adverse events ¹¹. FDA approved apitegromab as Isembyld on September 11, 2026, for SMA in adults and children aged 2 and older receiving an SMN2-targeted treatment ². It is the first myostatin-pathway drug approved anywhere, nearly three decades after myostatin was discovered, and it is approved as an add-on for one rare disease, not as a muscle builder.

Why more muscle has not meant better function

A pattern runs through these trials: muscle size moves more easily than muscle function. Domagrozumab raised muscle volume a little without improving stair climbing ³; ACE-031 nudged lean mass without a significant change in walking distance ¹; bimagrumab grew thigh muscle in sarcopenia but did not improve walking in inclusion body myositis ^{5 6}. In diseases where muscle is damaged, inflamed or poorly connected to nerves, adding bulk does not repair the underlying problem. That is part of why apitegromab was approved as an add-on to treatments that address SMA's cause, rather than on its own.

Follistatin: one gene-therapy study and a black market

Follistatin binds myostatin and activins. The only study that has given it to people did so as gene therapy: six men with Becker muscular dystrophy received a virus carrying the FS344 follistatin gene, injected into both thigh muscles. Four improved their six-minute walk, by 58, 125, 108 and 29 metres, two did not, and there were no adverse effects; biopsies showed less fibrosis ¹². That is a small, uncontrolled study of a gene delivered into muscle, not of a protein injected under the skin.

What is sold online as 'follistatin 344' or 'follistatin 315' is a different matter. When researchers analysed 17 black-market products with those labels, only nine contained follistatin at all, all in a tagged recombinant form with clumps of protein; others contained different growth peptides, such as MGF and GHRP-2 ¹³. A buyer has roughly even odds of getting follistatin, and no way of knowing what the rest contain without testing.

The GLP-1 muscle question

Interest in myostatin blockers has surged because of GLP-1 drugs. Semaglutide and tirzepatide produce large weight losses, a meaningful share of it lean tissue, and the hope is that adding a muscle-preserving drug would make weight loss healthier, especially for older people at risk of frailty. The bimagrumab-semaglutide trial is the most advanced test of that idea, and it reported weight loss, not long-term strength or function ⁸. None of the research peptides sold for this purpose, including follistatin, has been tested alongside a GLP-1 drug. Our article on GLP-1 side effects such as hair loss and facial volume covers related questions about body composition.

For athletes

All of these are prohibited at all times under section S4.3 of WADA's 2026 List, agents preventing activin receptor IIB activation. The List names ACE-031 as a decoy activin receptor, bimagrumab as an anti-activin receptor IIB antibody, follistatin as a myostatin-binding protein, and apitegromab, domagrozumab and landogrozumab as myostatin- or precursor-neutralising antibodies ¹⁴. That includes apitegromab even now it is approved; an athlete with SMA would need a therapeutic use exemption.

The bottom line

As of October 3, 2026, blocking the myostatin pathway in people has produced one approved drug, apitegromab, for spinal muscular atrophy alongside other treatment; one promising obesity candidate, bimagrumab, still in phase 2; and a list of stopped or failed programmes, starting with ACE-031's vascular side effects. Follistatin has been given to six men as gene therapy. The research products sold as follistatin or myostatin blockers have no human data, and half of those tested did not contain what they claimed.

Frequently asked questions

What happened to ACE-031?

Its trial in boys with Duchenne muscular dystrophy was stopped after the second dose level because of nosebleeds and dilated blood vessels, and development was suspended in 2013. It showed only non-significant trends towards benefit.

Is there an approved myostatin inhibitor?

Yes, as of September 11, 2026: apitegromab (Isembyld) is FDA-approved for spinal muscular atrophy in people aged 2 and older who are receiving an SMN2-targeted treatment.

Does follistatin 344 work?

It has been tested in people only as gene therapy, in six men with Becker muscular dystrophy. Injectable follistatin products have no human studies, and only 9 of 17 black-market products tested contained follistatin.

Can myostatin blockers prevent muscle loss on Ozempic?

That is being tested. In a phase 2 trial, bimagrumab with semaglutide produced more weight loss than either alone, and earlier work showed bimagrumab raised lean mass, but long-term effects on strength and function are unknown.

Related on Grey Peptides

• Apitegromab
• Bimagrumab
• Follistatin 344

Sources

1. Campbell, C., et al. (2017). Myostatin inhibitor ACE-031 treatment of ambulatory boys with Duchenne muscular dystrophy: Results of a randomized, placebo-controlled clinical trial. Muscle Nerve, 55(4), 458-464. PMID: 27462804
2. Grey Peptides encyclopedia entries for ACE-031 (development suspension and attributed mechanism) and apitegromab (FDA approval as Isembyld, BLA 761463, September 11, 2026). Read October 3, 2026.
3. Wagner, K. R., et al. (2020). Randomized phase 2 trial and open-label extension of domagrozumab in Duchenne muscular dystrophy. Neuromuscul Disord, 30(6), 492-502. PMID: 32522498
4. Golan, T., et al. (2018). LY2495655, an antimyostatin antibody, in pancreatic cancer: a randomized, phase 2 trial. J Cachexia Sarcopenia Muscle, 9(5), 871-879. PMID: 30051975
5. Rooks, D., et al. (2017). Treatment of Sarcopenia with Bimagrumab: Results from a Phase II, Randomized, Controlled, Proof-of-Concept Study. J Am Geriatr Soc, 65(9), 1988-1995. PMID: 28653345
6. Hanna, M. G., et al. (2019). Safety and efficacy of intravenous bimagrumab in inclusion body myositis (RESILIENT): a randomised, double-blind, placebo-controlled phase 2b trial. Lancet Neurol, 18(9), 834-844. PMID: 31397289
7. Heymsfield, S. B., et al. (2021). Effect of Bimagrumab vs Placebo on Body Fat Mass Among Adults With Type 2 Diabetes and Obesity: A Phase 2 Randomized Clinical Trial. JAMA Netw Open, 4(1), e2033457. PMID: 33439265
8. Heymsfield, S. B., et al. (2026). Bimagrumab plus semaglutide alone or in combination for the treatment of obesity: a randomized phase 2 trial. Nat Med, 32(3), 869-882. PMID: 41772149
9. Barrett, D., et al. (2021). A Randomized Phase 1 Safety, Pharmacokinetic and Pharmacodynamic Study of the Novel Myostatin Inhibitor Apitegromab (SRK-015): A Potential Treatment for Spinal Muscular Atrophy. Adv Ther, 38(6), 3203-3222. PMID: 33963971
10. Crawford, T. O., et al. (2024). Safety and Efficacy of Apitegromab in Patients With Spinal Muscular Atrophy Types 2 and 3: The Phase 2 TOPAZ Study. Neurology, 102(5), e209151. PMID: 38330285
11. Crawford, T. O., et al. (2025). 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. Lancet Neurol, 24(9), 727-739. PMID: 40818473
12. Mendell, J. R., et al. (2015). A phase 1/2a follistatin gene therapy trial for becker muscular dystrophy. Mol Ther, 23(1), 192-201. PMID: 25322757
13. Reichel, C., et al. (2019). Detection of black market follistatin 344. Drug Test Anal, 11(11-12), 1675-1697. PMID: 31758732
14. World Anti-Doping Agency. The 2026 Prohibited List, S4.3 Agents preventing activin receptor IIB activation (names ACE-031, bimagrumab, follistatin, apitegromab, domagrozumab and landogrozumab), in force January 1 to December 31, 2026. Read in full July 16, 2026.

Educational information, not medical advice. Each dose in this guide names its source, an approved label or a published study. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose.