GDF-8 Research

GDF-8 research describes a protein that restrains skeletal muscle growth rather than one that builds it. GDF-8 is myostatin, a negative regulator of skeletal muscle mass ^[1]. GDF-8 is a research compound and it is not for human consumption. No published or registered human study has administered myostatin protein to a person ^[26]. Almost the whole therapeutic literature on this pathway is about blocking myostatin rather than supplying it ^[11][14][20].

What GDF-8 is

GDF-8 is a protein rather than a small molecule, and no CAS number for it can be confirmed against PubChem ^[26]. PubChem returns no compound record for either the name myostatin or the name GDF-8, and holds the molecule only as a protein target entry ^[26]. That entry is a database record about a gene product, not a chemical registration and not an approval ^[26]. Any vendor listing that prints a CAS number for GDF-8 is printing an identifier that PubChem cannot tie to this protein ^[26].

The human precursor is 375 amino acids long, with residues 24 to 266 forming the propeptide and residues 267 to 375 the mature growth-factor chain ^[25]. The active molecule is a disulfide-linked homodimer of two mature chains ^[25].

In adult mice, circulating myostatin is not that mature dimer on its own. It circulates in a latent form that acid treatment can activate, which is an animal and in vitro finding ^[5]. That latent form is how the ligand is held inactive in the circulation of those mice ^[5]. Whether a supplied recombinant dimer behaves like the native latent complex is unstudied. That question is unresolved rather than settled in either direction.

What GDF-8 research shows about the direction of the biology

The founding animal study deleted the myostatin gene in mice and produced two to three fold increases in skeletal muscle mass ^[1]. In that mouse model, less myostatin gave more muscle. The same direction appears in cattle, where mutations in the myostatin gene explain the double-muscled Belgian Blue and Piedmontese breeds ^[2]. It appears in dogs, where a myostatin mutation increases muscle mass in whippets and enhances racing performance in heterozygotes ^[3]. In humans, a published case report describes a child with a myostatin mutation and gross muscle hypertrophy ^[4]. That report covers one child, so it establishes direction rather than effect size across people.

Myostatin-deficient mice are also leaner, with reduced fat accumulation as they age and partly suppressed fat gain in two genetic obesity models ^[8].

What happens when myostatin is raised

Systemic overexpression of myostatin in adult mice induced profound loss of both muscle and fat, which the authors described as analogous to human cachexia syndromes ^[5]. That experiment used implanted cells secreting myostatin, so it is sustained systemic elevation and not a single injection of purified protein ^[5]. The transgenic mouse models that followed are also overexpression designs and not injection studies ^[6][7].

Muscle-specific transgenic overexpression of myostatin produced lower skeletal muscle mass than wild type in male mice ^[6]. Cardiac-specific overexpression raised circulating myostatin several fold in mice and reduced the weight of the quadriceps, gastrocnemius, soleus and the heart itself ^[7].

Human evidence on administered GDF-8

There is no human evidence on administered GDF-8. A ClinicalTrials.gov query on myostatin as an intervention returned 34 registered studies on 2026-08-28 ^[26]. Every one of them either blocks the pathway or measures myostatin as a biomarker, and not one administers the protein ^[26]. Parallel PubMed searching surfaced no human administration report ^[26]. There is therefore no human pharmacokinetic, safety or tolerability record for administered myostatin ^[26]. A universal negative cannot be proven outright, and what these searches establish is an absence from the registered and published record ^[26].

Identity in this product class is a second problem. Analytical work on 14 black-market ACE-031 products found only 12 containing any protein reactive to the expected receptor antibody ^[23]. Mass spectrometry showed that all 12 held a different protein from the one they were sold as ^[23]. That study examined ACE-031 rather than GDF-8, so it is evidence about labeling accuracy in this class and not about GDF-8 itself ^[23].

Myostatin inhibitors are a separate literature

Every human trial of a myostatin-pathway drug tested a molecule that blocks myostatin or its receptor ^[26]. Those results describe the inhibitors and they do not describe GDF-8. Presenting them as GDF-8 findings would invert their meaning.

A single-dose Phase 1 study tested the receptor decoy ACE-031 in 48 healthy postmenopausal women ^[10]. In its highest dose group, total-body lean mass rose by 3.3% and thigh muscle volume by 5.1% ^[10]. A Phase 2 sarcopenia trial of the receptor antibody bimagrumab increased lean body mass by 6% over placebo and missed its primary physical-function endpoint at p=0.13 ^[11]. Its walking-distance and gait-speed secondaries also failed to separate ^[11]. A Phase 2 trial of the anti-myostatin antibody LY2495655 raised appendicular lean mass by 0.43 kg over placebo in 201 older weak fallers ^[13]. That trial pre-specified a two-sided alpha of 0.1 for its performance tests, and four performance differences fell below that threshold ^[13]. No effect was detected on the other performance measures ^[13].

The class has produced failed trials across eighteen years. Bimagrumab missed its primary endpoint at all three doses in a 251-participant inclusion body myositis trial, the largest randomized trial in that disease ^[17]. Its long-term extension found no improvement in mobility and was terminated early because the core study did not meet its primary endpoint ^[18]. Domagrozumab missed its primary endpoint in 120 boys with Duchenne muscular dystrophy, with no significant difference on any secondary clinical endpoint ^[19]. An open-label Phase Ib/IIa trial of domagrozumab in 19 patients with limb-girdle muscular dystrophy found no clear evidence supporting its efficacy in improving muscle strength or function ^[21]. That trial had no placebo arm ^[21]. The earliest trial in this class tested the antibody MYO-029 in 116 adults with muscular dystrophy in 2008 ^[20]. It showed no improvement on exploratory end points of muscle strength or function ^[20]. That trial was not powered to look for efficacy ^[20]. The taldefgrobep alfa program in patients with Duchenne muscular dystrophy was terminated after a pre-planned futility analysis indicated lack of efficacy ^[29]. That was a futility stop and not a safety stop ^[29]. Two registered bimagrumab trials were withdrawn rather than terminated, one with no documented reason and one for stated strategic business reasons ^[29].

Two trials in the class stopped early over safety findings. An ACE-031 trial in ambulatory boys with Duchenne muscular dystrophy was stopped after the second dosing regimen over epistaxis and telangiectasias, with only non-significant efficacy trends ^[15]. A pancreatic cancer trial of LY2495655 terminated its higher-exposure arm in 2014 over an imbalance in death rates, with an overall survival hazard ratio of 1.70 against placebo ^[16]. The lower-exposure arm was terminated later for futility, with a hazard ratio of 1.3 ^[16]. The authors concluded that the antibody did not confer clinical benefit in pancreatic cancer ^[16]. Among possibly drug-related adverse events in that trial, fatigue, diarrhea and anorexia were more common on LY2495655 than on placebo ^[16]. MYO-029 showed dose-limiting cutaneous hypersensitivity in its two highest cohorts ^[20]. In the older weak fallers trial, injection-site reactions occurred in 30% of the LY2495655 group and in 9% of placebo ^[13]. In the inclusion body myositis trial, muscle spasms were markedly more frequent on bimagrumab than on placebo, and diarrhea was more frequent as well ^[17]. A trial in 68 healthy older adults found no clinically relevant change in cardiac structure or function after six months of bimagrumab ^[22].

One late result is positive. Apitegromab met its primary endpoint in a Phase 3 spinal muscular atrophy trial, improving motor function by 1.8 points over placebo for the combined dose groups ^[14]. The comparison of the higher dose alone against placebo was not significant ^[14]. The significant result came from pooling the two dose groups ^[14].

Why the mass gains did not become function gains

An animal study of two independent myostatin-deficient mouse lines found larger muscles with no increase in maximum tetanic force ^[9]. Expressed per unit of muscle size, those muscles were weaker than wild type, with mitochondrial depletion and a shift in fiber type ^[9]. Lean mass rose reliably in the trials that measured it ^[10][11][13]. Function did not follow in the sarcopenia, inclusion body myositis, Duchenne or adult muscular dystrophy trials ^{[11][17][19][20]}.

Conflicts of interest in this literature

Sponsorship dominates the field, and both ACE-031 reports carry Acceleron Pharma employees as authors ^[10][15]. The bimagrumab series is Novartis-sponsored with overlapping author teams across five reports ^{[11][12][17][18][22]}. The LY2495655 trials are Eli Lilly ^[13][16], the domagrozumab trials are Pfizer ^[19][21], and the apitegromab Phase 3 was funded by Scholar Rock with sponsor employees among its authors ^[14]. The report of the halted ACE-031 trial closes by calling myostatin inhibition promising, an upbeat gloss on a study stopped early over a vascular safety signal ^[15].

The asymmetry matters more than the individual disclosures. Every commercial program in the myostatin pathway aims to block myostatin or its receptor, and none has ever developed myostatin itself as a therapeutic. The absence of human administration data is therefore not a funding gap waiting to be filled.

Regulatory status

No myostatin-selective agent is approved for any indication anywhere. openFDA returned no United States drug label for myostatin and none for apitegromab on 2026-08-28 ^[26]. Apitegromab remains under FDA review after a Complete Response Letter issued in September 2025 ^[28]. That letter cited inspection findings at a third-party fill-finish facility, and no efficacy or safety concern about the drug ^[28]. Fast Track, Orphan Drug and similar designations are not approvals.

Two ligand traps built from activin type II receptor domains hold United States approvals, and myostatin signals through that receptor family ^[24][27]. Luspatercept is a fusion of a modified activin receptor type IIB domain with a human IgG1 Fc, approved for anemia in beta thalassemia and in myelodysplastic syndromes ^[27]. Its label states that it is not indicated as a substitute for red blood cell transfusions in patients who require immediate correction of anemia ^[27]. Sotatercept is an activin receptor type IIA-Fc fusion protein approved for pulmonary arterial hypertension in adults ^[27]. Neither label names myostatin and neither drug is approved for a muscle indication ^[27]. Both trap ligands rather than supply one, so neither is GDF-8 ^[27].

GDF-8 is not named on the 2026 WADA Prohibited List ^[28]. Myostatin inhibitors appear there under the section covering agents that prevent activin receptor IIB activation ^[23][28]. The list's non-approved substances section sets two conditions together ^[28]. It covers a substance that no other section of the list addresses, and that no governmental regulatory health authority has approved for human therapeutic use ^[28]. A substance meeting both is prohibited at all times ^[28]. Recombinant GDF-8 meets both, because no other section names it and no authority has approved it, so it is prohibited at all times ^[28].

Conclusion

Myostatin restrains muscle growth in mice, in cattle, in dogs and in a published human case report ^[1][2][3][4]. Raising it in mice reduced muscle mass, and in one study reduced fat as well ^[5][6][7]. The human trial record for drugs in this pathway belongs to molecules that block myostatin or its receptor, most of which failed on function ^{[11][17][19][20]}. GDF-8 has no human evidence base of its own for administration ^[26].

Frequently Asked Questions

Has GDF-8 been given to a person in a study? No published or registered human study has administered myostatin protein to a person ^[26]. A ClinicalTrials.gov query returned 34 registered myostatin-intervention studies, and every one either blocks the pathway or measures myostatin as a biomarker ^[26]. There is no human pharmacokinetic, safety or tolerability record for administered myostatin ^[26].

Do myostatin-inhibitor trial results apply to GDF-8? They do not, and presenting them as GDF-8 findings would invert their meaning. Every human trial of a myostatin-pathway drug tested a molecule that blocks myostatin or its receptor rather than supplying it ^[26]. The lean-mass gains in those trials came from blocking myostatin or the receptor it signals through ^[10][11][13].

Is anything in the myostatin pathway approved? No myostatin-selective agent is approved for any indication anywhere, and openFDA returned no United States label for myostatin or apitegromab on 2026-08-28 ^[26]. Two ligand traps aimed at the same receptor family hold United States approvals ^[27]. Luspatercept is approved for anemia in beta thalassemia and in myelodysplastic syndromes, and sotatercept for pulmonary arterial hypertension in adults ^[27]. Neither label names myostatin ^[27].

References

1. 1

   McPherron AC, Lawler AM, Lee SJ. Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature. 1997 May 1;387(6628):83-90. PMID 9139826. DOI: 10.1038/387083a0 (esummary re-run live 2026-08-28)
2. 2

   McPherron AC, Lee SJ. Double muscling in cattle due to mutations in the myostatin gene. Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12457-61. PMID 9356471. DOI: 10.1073/pnas.94.23.12457
3. 3

   Mosher DS, Quignon P, Bustamante CD, et al. A mutation in the myostatin gene increases muscle mass and enhances racing performance in heterozygote dogs. PLoS Genet. 2007 May 25;3(5):e79. PMID 17530926. DOI: 10.1371/journal.pgen.0030079
4. 4

   Schuelke M, Wagner KR, Stolz LE, et al. Myostatin mutation associated with gross muscle hypertrophy in a child. N Engl J Med. 2004 Jun 24;350(26):2682-8. PMID 15215484. DOI: 10.1056/NEJMoa040933 (the PubMed record carries no abstract, so only the title claim of gross muscle hypertrophy in a child is used; senior author Se-Jin Lee)
5. 5

   Zimmers TA, Davies MV, Koniaris LG, et al. Induction of cachexia in mice by systemically administered myostatin. Science. 2002 May 24;296(5572):1486-8. PMID 12029139. DOI: 10.1126/science.1069525 (abstract read live 2026-08-28: "myostatin circulates in the blood of adult mice in a latent form that can be activated by acid treatment" and systemic overexpression "induce[d] profound muscle and fat loss analogous to that seen in human cachexia syndromes"; senior author Se-Jin Lee)
6. 6

   Reisz-Porszasz S, Bhasin S, Artaza JN, et al. Lower skeletal muscle mass in male transgenic mice with muscle-specific overexpression of myostatin. Am J Physiol Endocrinol Metab. 2003 Oct;285(4):E876-88. PMID 12824080. DOI: 10.1152/ajpendo.00107.2003
7. 7

   Heineke J, Auger-Messier M, Xu J, et al. Genetic deletion of myostatin from the heart prevents skeletal muscle atrophy in heart failure. Circulation. 2010 Jan 26;121(3):419-25. PMID 20065166. DOI: 10.1161/CIRCULATIONAHA.109.882068 (abstract read live: cardiac-specific overexpression raised circulating myostatin 3- to 4-fold and reduced the weight of quadriceps, gastrocnemius, soleus and the heart)
8. 8

   McPherron AC, Lee SJ. Suppression of body fat accumulation in myostatin-deficient mice. J Clin Invest. 2002 Mar;109(5):595-601. PMID 11877467. DOI: 10.1172/JCI13562 (the two obesity models are agouti lethal yellow and Lep ob/ob)
9. 9

   Amthor H, Macharia R, Navarrete R, et al. Lack of myostatin results in excessive muscle growth but impaired force generation. Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):1835-40. PMID 17267614. DOI: 10.1073/pnas.0604893104 (carries an erratum at Proc Natl Acad Sci U S A 2007 Mar 6;104(10):4240; the two lines are constitutive Mstn-null and the Berlin High Line compact mutant)
10. 10

    Attie KM, Borgstein NG, Yang Y, et al. A single ascending-dose study of muscle regulator ACE-031 in healthy volunteers. Muscle Nerve. 2013 Mar;47(3):416-23. PMID 23169607. DOI: 10.1002/mus.23539 (Acceleron Pharma employee authors; the 3.3% and 5.1% figures are from the highest dose group at day 29)
11. 11

    Rooks D, Swan T, Goswami B, et al. Bimagrumab vs optimized standard of care for treatment of sarcopenia in community-dwelling older adults: a randomized clinical trial. JAMA Netw Open. 2020 Oct 1;3(10):e2020836. PMID 33074327. DOI: 10.1001/jamanetworkopen.2020.20836 (SPPB P=.13, 6-minute walk P=.16, gait speed P=.16, lean body mass difference 6%, P<.001; conflict statement lists 14 Novartis employees and multiple bimagrumab patents)
12. 12

    Heymsfield SB, Coleman LA, Miller R, et al. 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. 2021 Jan 4;4(1):e2033457. PMID 33439265. DOI: 10.1001/jamanetworkopen.2020.33457 (cited here only for Novartis sponsorship; carries two published errata, PMID 33576812. and PMID 33646308.; all intervals in the paper are 80% confidence intervals)
13. 13

    Becker C, Lord SR, Studenski SA, et al. Myostatin antibody (LY2495655) in older weak fallers: a proof-of-concept, randomised, phase 2 trial. Lancet Diabetes Endocrinol. 2015 Dec;3(12):948-57. PMID 26516121. DOI: 10.1016/S2213-8587(15)00298-3 (aLBM difference 0.43 kg, 95% CI 0.192 to 0.660, p<0.0001; performance tests were pre-specified at a two-sided alpha of 0.1, and the four differences below it were four-step stair climb p=0.093, 12-step stair climb p=0.011, chair rise with arms p=0.054 and fast gait speed p=0.088; "No effect was detected for other performance-based measures"; injection-site reactions 30% on LY2495655 vs 9% on placebo, p<0.0001; funding Eli Lilly and Company)
14. 14

    Crawford TO, Servais L, Mercuri E, et al. 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. 2025 Sep;24(9):727-739. PMID 40818473. DOI: 10.1016/S1474-4422(25)00225-X (combined-dose HFMSE difference 1.8, 95% CI 0.30 to 3.32, p=0.019; higher dose alone 1.4, 95% CI -0.34 to 3.13, p=0.11; funding Scholar Rock; six Scholar Rock employees among the authors and the first author is lead principal investigator of the sponsor's phase 2 TOPAZ trial)
15. 15

    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 Apr;55(4):458-464. PMID 27462804. DOI: 10.1002/mus.25268 (abstract read live: "The study was stopped after the second dosing regimen due to potential safety concerns of epistaxis and telangiectasias"; its closing sentence is "Myostatin inhibition is a promising therapeutic approach for DMD"; four Acceleron authors including Attie and Sherman)
16. 16

    Golan T, Geva R, Richards D, et al. LY2495655, an antimyostatin antibody, in pancreatic cancer: a randomized, phase 2 trial. J Cachexia Sarcopenia Muscle. 2018 Oct;9(5):871-879. PMID 30051975. DOI: 10.1002/jcsm.12331 (125 randomized; higher-exposure arm terminated August 2014 for an imbalance in death rates, lower-exposure arm terminated January 2015 for futility; overall survival hazard ratios 1.70, 90% CI 1.1 to 2.7, and 1.3, 90% CI 0.82 to 2.1; abstract read live 2026-08-28: "Among possibly drug-related adverse events, fatigue, diarrhoea, and anorexia were more common in LY2495655-treated than in placebo-treated patients"; three Eli Lilly authors)
17. 17

    Hanna MG, Badrising UA, Benveniste O, et al. Safety and efficacy of intravenous bimagrumab in inclusion body myositis (RESILIENT): a randomised, double-blind, placebo-controlled phase 2b trial. Lancet Neurol. 2019 Sep;18(9):834-844. PMID 31397289. DOI: 10.1016/S1474-4422(19)30200-5 (251 participants; week 52 6-minute walk differences 17.6 m p=0.22, 18.6 m p=0.19 and -1.3 m p=0.93, reported with 99% confidence intervals; the authors call it the largest randomised controlled trial done in people with inclusion body myositis; muscle spasms 51%, 68% and 40% across the three dose groups vs 21% on placebo, and diarrhoea also markedly more frequent on drug; funding Novartis Pharma)
18. 18

    Amato AA, Hanna MG, Machado PM, et al. Efficacy and safety of bimagrumab in sporadic inclusion body myositis: long-term extension of RESILIENT. Neurology. 2021 Mar 23;96(12):e1595-e1607. PMID 33597289. DOI: 10.1212/WNL.0000000000011626 (abstract read live: extended treatment "did not provide clinical benefits in terms of improvement in mobility" and "The extension study was terminated early due to core study not meeting its primary endpoint")
19. 19

    Wagner KR, Abdel-Hamid HZ, Mah JK, et al. Randomized phase 2 trial and open-label extension of domagrozumab in Duchenne muscular dystrophy. Neuromuscul Disord. 2020 Jun;30(6):492-502. PMID 32522498. DOI: 10.1016/j.nmd.2020.05.002 (120 boys; 4-stair-climb difference 0.27 s, 95% CI -7.4 to 7.9, p=0.94; "There were no significant between-group differences in any secondary clinical endpoints"; carries a corrigendum, PMID 33451933.; Pfizer authors)
20. 20

    Wagner KR, Fleckenstein JL, Amato AA, et al. A phase I/II trial of MYO-029 in adult subjects with muscular dystrophy. Ann Neurol. 2008 May;63(5):561-71. PMID 18335515. DOI: 10.1002/ana.21338 (116 subjects; "There were no improvements noted in exploratory end points of muscle strength or function, but the study was not powered to look for efficacy"; dose-limiting cutaneous hypersensitivity occurred in the two highest cohorts)
21. 21

    Leung DG, Bocchieri AE, Ahlawat S, et al. A phase Ib/IIa, open-label, multiple ascending-dose trial of domagrozumab in fukutin-related protein limb-girdle muscular dystrophy. Muscle Nerve. 2021 Aug;64(2):172-179. PMID 33961310. DOI: 10.1002/mus.27259 (19 patients; open-label multiple-ascending-dose phase Ib/IIa design with no placebo arm; abstract read live 2026-08-28: "there was no clear evidence supporting its efficacy in improving muscle strength or function". The previous version of this annotation quoted "There were no significant between-group differences in the strength, functional, or imaging outcomes studied", which is not the wording the live abstract carries and which implied a controlled comparison this trial did not run; see reviewer flag 28. Pfizer authors)
22. 22

    Rooks D, Yates DP, Neelakantham S, et al. Cardiac safety of chronic inhibition of the myostatin-activin pathway with bimagrumab in healthy older adults. J Clin Endocrinol Metab. 2026 Aug 13;111(9):2573-2582. PMID 41873146. DOI: 10.1210/clinem/dgag091 (68 healthy adults aged 60 to 86; LVMI 1.6 g/m2, 90% CI -0.2 to 3.4, P=.148; "no effect on cardiac structure or function"; Novartis authors)
23. 23

    Reichel C, Filip T, Gmeiner G, Thevis M. Gel electrophoretic detection of black market ACE-031. Drug Test Anal. 2025 Oct;17(10):1934-1946. PMID 40312924. DOI: 10.1002/dta.3898 (abstract read live: "Of 14 tested products, only 12 contained an ACVR2B-immunoreactive protein" and those 12 "contained the full-length human activin receptor IIB instead of ACE-031"; the paper states ACE-031 "is banned according to chapter S4.3" of the WADA list; the animal arm was in rats because dosing humans with black market product was judged unethical)
24. 24

    Tsuchida K. Clinical applications of ligand traps targeting activin type II receptors. Antiinflamm Antiallergy Agents Med Chem. 2026 Jan 2. PMID 41487000. DOI record confirmed by esummary on 2026-08-28; volume and pages not yet assigned in the PubMed record (states that luspatercept and sotatercept are the two approved ligand traps in this class)
25. 25

    UniProt entry O14793, Growth/differentiation factor 8, Homo sapiens, retrieved live 2026-08-28. Sequence length 375. Feature table: propeptide residues 24 to 266; chain residues 267 to 375, "Growth/differentiation factor 8". Subunit comment: "Homodimer; disulfide-linked". Gene MSTN, NCBI Gene 2660.
26. 26

    Database and registry sweep, run live for this draft on 2026-08-28. PubChem PUG-REST compound-name lookups for "myostatin" and for "GDF-8" both return PUGREST.NotFound, "No CID found"; the only PubChem holding is a protein target record for UniProt O14793, which is a target entry and not a compound record. ClinicalTrials.gov API v2 with countTotal=true and query.intr=myostatin returns totalCount 34; the intervention names across all 34 were retrieved and inspected, and every study either administers an inhibitor (apitegromab, SRK-015, RO7239361 taldefgrobep alfa, PF-06252616 domagrozumab, LY2495655, PINTA 745, trevogrumab, AAV9-follistatin, IBIO-600) or measures myostatin as an outcome or biomarker alongside exercise, nutrition, surgery or metformin. None administers myostatin protein. openFDA drug/label queries field-qualified against openfda.substance_name for "myostatin" and against openfda.generic_name for "apitegromab" both return NOT_FOUND. PubMed E-utilities searches for human administration of recombinant myostatin surfaced no administration study.
27. 27

    openFDA drug/label records retrieved live 2026-08-28. REBLOZYL (luspatercept-aamt), Celgene Corporation: description field reads "a receptor fusion protein consisting of a modified extracellular domain of the human activin receptor type IIB linked to a human IgG1 Fc domain"; mechanism field reads "binds several endogenous TGF-beta superfamily ligands, thereby diminishing Smad2/3 signaling"; indications cover anemia in beta thalassemia and in myelodysplastic syndromes; Limitations of Use read "REBLOZYL is not indicated for use as a substitute for RBC transfusions in patients who require immediate correction of anemia". WINREVAIR (sotatercept-csrk), Merck Sharp & Dohme LLC: mechanism field reads "a recombinant activin receptor type IIA-Fc (ActRIIA-Fc) fusion protein"; indicated for adults with pulmonary arterial hypertension. Neither label mentions myostatin anywhere, and neither carries a muscle indication.
28. 28

    Regulatory and prohibited-list record. WADA 2026 Prohibited List: the heading "S4.3. AGENTS PREVENTING ACTIVIN RECEPTOR IIB ACTIVATION" covers follistatin, myostatin propeptide, apitegromab, domagrozumab, landogrozumab, stamulumab, ACE-031 and bimagrumab, and section S0 NON-APPROVED SUBSTANCES covers "Any pharmacological substance which is not addressed by any of the subsequent sections of the List and with no current approval by any governmental regulatory health authority for human therapeutic use", prohibited at all times. The S4.3 placement is independently corroborated by reference 23, whose text was read live. See reviewer flag 6 on the provenance of the S0 wording. Apitegromab regulatory sequence: FDA Complete Response Letter dated 2025-09-23, stated to relate solely to inspection observations at a third-party fill-finish facility and citing no efficacy or safety concern; Type C meeting 2026-03-03; resubmission with a second US fill-finish site; PDUFA action date 2026-09-30. See reviewer flag 7 on the provenance of that sequence and on its expiry date.
29. 29

    ClinicalTrials.gov registry records for program terminations and withdrawals in this class, carried from the dossier, which marks all three VERIFIED via API v2 on 2026-08-28. They were not independently re-queried for this draft; see reviewer flag 28. Taldefgrobep alfa NCT02515669, status TERMINATED, WhyStopped "A pre-planned futility analysis indicated lack of efficacy in study NCT03039686 and led to discontinuation of both ongoing studies in DMD." Bimagrumab in mechanically ventilated patients NCT01868685, status WITHDRAWN, no reason documented. Bimagrumab with tirzepatide NCT06901349, status WITHDRAWN, WhyStopped "Study terminated for strategic business reasons." The taldefgrobep alfa spinal muscular atrophy Phase 3 result is a sponsor investor announcement and is not carried on this page; see reviewer flag 13.