ACTH 1-39 Research

ACTH 1-39, also called corticotropin, is the full-length adrenocorticotropic hormone, a 39-residue peptide cleaved from proopiomelanocortin in the pituitary ^[22]. It is unusual among catalogue peptides, because corticotropin holds live FDA approvals in the United States ^[1][2]. That history is often read as proof of a strong evidence base. An independent scoping review found few randomized human trials supporting clinical benefit for most of those approved indications ^[3].

What ACTH 1-39 is

PubChem lists corticotropin as CID 16132265, formula C207H308N56O58S, molecular weight near 4541 ^[4]. Seractide, the synthetic human-sequence peptide, has its own record, CID 90488848, returning the identical formula, weight and structured human sequence ^[4]. Nothing structural separates the two records ^[4].

CAS 9002-60-2 resolves to CID 16132265, whose synonyms include porcine deamidated names and human ACTH 1-39 names alike ^[4]. Those are names, not a structural assignment, so the CAS does not pin down a species or variant ^[4]. Material sold as ACTH 1-39 is a research chemical whose variant the catalogue data does not state.

Molecules that are not ACTH 1-39

Cosyntropin, also called tetracosactide, is ACTH 1-24, a shorter fully synthetic peptide with separate US approvals ^[5]. Those are diagnostic only, for screening adrenocortical insufficiency, and cannot be read across to ACTH 1-39 ^[5]. The ICISS infantile spasms trial is a related source of confusion, because its hormonal arms used prednisolone or tetracosactide depot, so it contains no ACTH 1-39 ^[6].

How ACTH 1-39 acts

The Acthar Gel label states that corticotropin stimulates the adrenal cortex to secrete cortisol, corticosterone and aldosterone ^[1]. It says the product is also reported to bind melanocortin receptors ^[1]. That wording describes the finished gel, not the isolated peptide ^[1]. It states plainly that the mechanism of action in infantile spasms is unknown ^[1]. A narrative review argued that ACTH acts through melanocortin pathways on immune and glial cells, independently of corticosteroid output ^[7]. That is a hypothesis set out in a review, not a result from a controlled human trial ^[7].

A phase 1 study in healthy human volunteers compared the approved gel with a synthetic ACTH 1-24 depot ^[8]. A companion paper pooled data from two phase 1 studies and reported lower free cortisol and steroidogenic exposure from the approved gel ^[9]. That comparator exposure came from a population model and a simulated dose, not a head-to-head arm ^[9]. Both papers were sponsored and authored by the manufacturer of the approved product ^[8][9].

Regulatory status of ACTH 1-39 in the United States

Corticotropin is an approved active ingredient in the United States ^[1][2]. Two current FDA labels carry it, Acthar Gel under NDA008372 and Purified Cortrophin Gel under NDA008975 ^[1][2]. Counted by Drugs@FDA application instead, three sit in prescription marketing status, adding H.P. Acthar Gel under NDA022432 ^[23].

Approval does not extend to a synthetic ACTH 1-39 peptide ^[1][2][23]. A research vial more likely holds seractide, the synthetic human-sequence form, and a Drugs@FDA query on that ingredient returns no record ^[23]. Such a laboratory chemical is neither approved product, and is not for human use.

Neither approved product is a pure ACTH 1-39 peptide ^[1][2]. The Acthar Gel label describes a naturally sourced complex mixture of ACTH analogs and other pituitary peptides ^[1]. It names N-25 deamidated porcine ACTH 1-39 as a major component in gelatin ^[1]. The Cortrophin label likewise describes a porcine mixture of ACTH and related pituitary peptides in gelatin ^[2]. Any clinical result from either product therefore describes a gelatin depot mixture, not a synthetic single peptide ^[1][2].

The two products are not approved for the same conditions ^[1][2]. Acthar Gel alone is indicated for infantile spasms, and both labels cover acute exacerbations of multiple sclerosis ^[1][2]. Both also list rheumatic, collagen, dermatologic, allergic, ophthalmic, respiratory and edematous indications ^[1][2]. The specific conditions inside those shared categories differ, and Cortrophin names acute gouty arthritis, severe psoriasis, atopic dermatitis and allergic conjunctivitis, which Acthar Gel does not ^[1][2]. A bare openFDA substance-name search returns 66 records, only two with an application number, and the other 64 unapproved oral products ^[10].

Human research

An independent scoping review examined the clinical evidence behind corticotropin's FDA-approved indications ^[3]. It included 41 studies and 2235 participants, 19 of them single-arm or comparing only corticotropin regimens against each other ^[3]. It concluded that few randomized human trials support clinical benefit for most approved indications ^[3]. Most randomized human trials in it did not find corticotropin superior to corticosteroids for multiple sclerosis relapses or infantile spasms ^[3]. Blinded human trials showed similar or greater adverse effects than corticosteroids ^[3]. The original approval predates modern FDA efficacy review standards ^[3].

One human trial in infantile spasms found corticotropin superior to a corticosteroid comparator ^[11]. It was a prospective randomized single-blind trial in 29 enrolled infants ^[11]. Corticotropin beat prednisone on blinded clinical and EEG response, at 13 of 15 against 4 of 14 ^[11]. The scoping review identifies it as the only such trial in its infantile spasms set ^[3].

Modern human trials in other approved indications have mostly failed ^[12][13][14]. A randomized human trial in childhood nephrotic syndrome stopped at a planned interim analysis for lack of efficacy ^[12]. Relapse occurred in 14 of 15 children on corticotropin and 15 of 16 controls ^[12]. A phase 4 human trial in systemic lupus erythematosus missed its primary endpoint at p=0.5762, and its favorable findings were post hoc ^[13]. A randomized human trial in acute optic neuritis found no difference against methylprednisolone on its primary retinal outcome ^[14].

A human trial in rheumatoid arthritis drew its headline response rate from an uncontrolled open-label run-in, measured against baseline rather than placebo ^[15]. Only its randomized withdrawal phase was controlled, and the effect there was modest but statistically significant ^[15]. A phase 4 human trial in pulmonary sarcoidosis was terminated early for low enrollment ^[16]. Its authors state that this precluded statistical analysis, and the paper still reports favorable descriptive trends with no p-values ^[16].

A phase 2/3 human trial in amyotrophic lateral sclerosis was terminated on the recommendation of its independent data and safety monitoring board ^[17]. On the primary functional rating scale, the corticotropin arm declined further from baseline by week 36 than placebo did ^[17]. The double-blind arms were uneven, 95 on corticotropin and 47 on placebo ^[17]. Serious adverse events affected 13 and 6 of them, a similar proportion in each arm, and posted deaths were 2 and 3 ^[17]. Its results exist only as a registry posting, with no peer-reviewed publication ^[17].

Several other registered human studies of corticotropin were terminated or withdrawn, in multiple sclerosis, uveitis, ARDS, sarcoidosis and rheumatoid arthritis ^[24]. Where a reason is posted it is recruitment, logistics, funding or a company decision, not demonstrated futility ^[24]. One completed human fatigue study in relapsing multiple sclerosis posted scores worse on corticotropin than placebo, at 8 participants ^[24].

The older human multiple sclerosis literature is thin: a placebo-controlled cooperative study reported in 1970, and a 1989 comparison ^[18][19]. That 1989 study was a double-blind randomized trial in 61 patients with acute relapse ^[19]. It found no difference between ACTH and methylprednisolone on rate of recovery or final outcome ^[19]. The Acthar Gel label states that controlled trials showed the product speeds resolution of acute exacerbations ^[1]. The same section states there is no evidence it affects the ultimate outcome or natural history ^[1].

Preclinical research

One animal study reported that ACTH gel reduced toxic SOD1 protein in transgenic mice modeling amyotrophic lateral sclerosis ^[20]. That mouse finding did not carry over into people ^[17].

Conflicts of interest in this literature

The lupus, rheumatoid arthritis, sarcoidosis and phase 1 pharmacology papers all carry manufacturer sponsorship or manufacturer employees among their authors ^{[8][9][13][15][16]}. The lupus paper missed its primary endpoint and still concluded that the results support the product's utility ^[13]. The sarcoidosis paper concluded in favor of trends it had already said could not be analyzed statistically ^[16]. The melanocortin mechanism review also carries consulting and grant ties to the manufacturer ^[7].

Publication bias here is documented, not theoretical, as that unpublished ALS trial shows ^[17]. An analysis of US Medicare data found that 207 of 235 frequent prescribers received corticotropin-related payments from the manufacturer ^[21]. Every $10,000 in payments was associated with a 7.9% rise in Medicare corticotropin spending, and no such association appeared for synthetic corticosteroids ^[21]. The most deflationary sources here are the independent ones ^[3][12][14].

Current directions and limitations

The central limitation is a mismatch between what was studied and what a research vial contains ^[1][2][4]. The melanocortin argument also remains unconfirmed where it was tested most directly in people, the optic neuritis trial ^[7][14].

Conclusion

Corticotropin is a genuinely approved active ingredient resting on a weak modern evidence base ^[1][2][3]. Its clearest human result against a corticosteroid comparator is still a small infantile spasms trial published in 1996 ^[3][11]. Recent controlled human trials in other approved indications largely failed, stopped early, or went unpublished ^{[12][13][14][16][17]}.

Evidence and identity FAQ

Is ACTH 1-39 approved for human therapeutic use? Corticotropin is approved in the United States as the active ingredient of Acthar Gel and Purified Cortrophin Gel ^[1][2]. Neither is a pure ACTH 1-39 peptide, and both are porcine-derived gelatin mixtures ^[1][2]. The synthetic human-sequence form, seractide, holds no US approval ^[23]. A research-grade peptide supplied as a laboratory chemical is not for human use.

Is ACTH 1-39 the same as cosyntropin or tetracosactide? No, those are names for ACTH 1-24, a shorter fully synthetic peptide whose separate US approvals are diagnostic only ^[5].

Has the positive infantile spasms result been replicated? An independent scoping review identifies that 1996 trial as the only infantile spasms trial in its set that found corticotropin significantly superior to a corticosteroid ^[3][11].

References

1. 1

   FDA prescribing information, Acthar Gel (repository corticotropin injection), NDA008372, Mallinckrodt ARD LLC. Label effective 2026-07-15, retrieved live from the openFDA drug/label API.
2. 2

   FDA prescribing information, Purified Cortrophin Gel (repository corticotropin injection), NDA008975, ANI Pharmaceuticals. Label effective 2026-02-09, retrieved live from the openFDA drug/label API.
3. 3

   Tran KA, Harrod C, Bourdette DN, et al. Characterization of the Clinical Evidence Supporting Repository Corticotropin Injection for FDA-Approved Indications: A Scoping Review. JAMA Intern Med. 2022;182(2):206-217. PMID 34902005.
4. 4

   PubChem, National Library of Medicine. Compound records CID 16132265 (corticotropin, CAS 9002-60-2) and CID 90488848 (seractide, CAS 12279-41-3). Both return MolecularFormula C207H308N56O58S and MolecularWeight 4541 via PUG-REST, and both carry the same structured Sequence field, SYSMEHFRWGKPVGKKRRPVKVYPNGAEDESAEAFPLEF, in their PUG-View records. The porcine and human synonyms cited are from the PUG-View record for CID 16132265.
5. 5

   FDA prescribing information, Cortrosyn (cosyntropin) for injection, NDA016750, Amphastar, and cosyntropin for injection, ANDA202147, Sandoz. Retrieved live from the openFDA drug/label API.
6. 6

   O'Callaghan FJ, Edwards SW, Alber FD, et al. Safety and effectiveness of hormonal treatment versus hormonal treatment with vigabatrin for infantile spasms (ICISS). Lancet Neurol. 2017;16(1):33-42. PMID 27838190.
7. 7

   Arnason BG, Berkovich R, Catania A, Lisak RP, Zaidi M. Mechanisms of action of adrenocorticotropic hormone and other melanocortins relevant to the clinical management of patients with multiple sclerosis. Mult Scler. 2013;19(2):130-136. PMID 23034287.
8. 8

   Poola N, Due B, Wright D, Brooks LR, Zaman F. Pharmacokinetics and Pharmacodynamics of Repository Corticotropin Injection Compared With Synthetic ACTH(1-24) Depot and Methylprednisolone in Healthy Subjects. Clin Pharmacol Drug Dev. 2022;11(4):502-515. PMID 34528408.
9. 9

   Wang X, Pham L, Poola N, Brooks LR, Due B. Comparison of Steroidogenic Exposure Following the Administration of Repository Corticotropin Injection With a Synthetic ACTH(1-24) Depot and Methylprednisolone. Clin Pharmacol Drug Dev. 2021;10(7):777-788. PMID 33369276.
10. 10

    openFDA drug/label API, live query 2026-08-28. search=openfda.substance_name:"CORTICOTROPIN" returns 66 records; 2 carry an application_number (NDA008372, NDA008975) and the other 64 have route ORAL and no application number. Of those 64, 61 describe themselves as homeopathic; the remaining 3 are unapproved OTC oral products (GUNA-GERIATRICS, Thinnr BOOST, Thinnr PROTOCOL).
11. 11

    Baram TZ, Mitchell WG, Tournay A, Snead OC, Hanson RA, Horton EJ. High-dose corticotropin (ACTH) versus prednisone for infantile spasms: a prospective, randomized, blinded study. Pediatrics. 1996;97(3):375-379. PMID 8604274.
12. 12

    Wang CS, Travers C, McCracken C, et al. Adrenocorticotropic Hormone for Childhood Nephrotic Syndrome: The ATLANTIS Randomized Trial. Clin J Am Soc Nephrol. 2018;13(12):1859-1865. PMID 30442868.
13. 13

    Askanase AD, Zhao E, Zhu J, Bilyk R, Furie RA. Repository Corticotropin Injection for Persistently Active Systemic Lupus Erythematosus: Results from a Phase 4, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial. Rheumatol Ther. 2020;7(4):893-908. PMID 32996096. Erratum: Rheumatol Ther. 2021;8(4):1915. PMID 34460089.
14. 14

    Bennett JL, Grove NC, Johnson RK, et al. A Randomized Prospective Trial Comparing Repository Corticotropin Injection and Intravenous Methylprednisolone for Neuroprotection in Acute Optic Neuritis. J Neuroophthalmol. 2023;43(3):323-329. PMID 37261907.
15. 15

    Fleischmann R, Furst DE, Connolly-Strong E, Liu J, Zhu J, Brasington R. Repository Corticotropin Injection for Active Rheumatoid Arthritis Despite Aggressive Treatment: A Randomized Controlled Withdrawal Trial. Rheumatol Ther. 2020;7(2):327-344. PMID 32185745.
16. 16

    Mirsaeidi M, Baughman RP, Sahoo D, Tarau E. Results From a Phase 4, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Repository Corticotropin Injection for the Treatment of Pulmonary Sarcoidosis. Pulm Ther. 2023;9(2):237-253. PMID 37072607.
17. 17

    ClinicalTrials.gov, NCT03068754, retrieved live 2026-08-28. Status TERMINATED as recommended by the study's independent Data and Safety Monitoring Board; 143 enrolled; primary outcome ALSFRS-R at Baseline and Week 36. No PubMed publication of this trial was located.
18. 18

    Rose AS, Kuzma JW, Kurtzke JF, et al. Cooperative study in the evaluation of therapy in multiple sclerosis. ACTH vs. placebo, final report. Neurology. 1970;20(5):1-59. PMID 4314823.
19. 19

    Thompson AJ, Kennard C, Swash M, et al. Relative efficacy of intravenous methylprednisolone and ACTH in the treatment of acute relapse in MS. Neurology. 1989;39(7):969-971. PMID 2544829.
20. 20

    Arrat H, Lukas TJ, Siddique T. ACTH (Acthar Gel) Reduces Toxic SOD1 Protein Linked to Amyotrophic Lateral Sclerosis in Transgenic Mice: A Novel Observation. PLoS One. 2015;10(5):e0125638. PMID 25955410.
21. 21

    Hartung DM, Johnston KA, Cohen DM, Nguyen T, Deodhar AA, Bourdette DN. Industry Payments to Physician Specialists Who Prescribe Repository Corticotropin. JAMA Netw Open. 2018;1(2):e180482. PMID 30646086.
22. 22

    UniProt entry P01189, human pro-opiomelanocortin. The Corticotropin peptide feature is annotated at residues 138-176 of the precursor, a length of 39 residues. Retrieved live from rest.uniprot.org.
23. 23

    openFDA Drugs@FDA API, live query 2026-08-28. products.active_ingredients.name:"CORTICOTROPIN" returns NDA008372, NDA022432 and NDA008975 in marketing_status Prescription. The same query on "SERACTIDE" returns NOT_FOUND.
24. 24

    ClinicalTrials.gov, live queries 2026-08-28. Terminated or withdrawn corticotropin studies include NCT03126760 (multiple sclerosis), NCT03656692 (uveitis), NCT02113735 (ARDS), NCT01950234 (progressive multiple sclerosis), NCT02523092 (sarcoidosis) and NCT01984268 (rheumatoid arthritis). Posted whyStopped values are recruitment difficulties, logistical challenges, discontinued funding, a company decision or a sponsor closing the study; NCT01984268 posts no reason. NCT02315872 is COMPLETED with posted fatigue scores worse on ACTH than placebo, enrollment 8.