Corticotropin (Acthar Gel)

Written by The Peptide Record editorialClinical review not yet completedLast reviewed 12 September 2026

Acthar Gel is a real, and remarkably old, approved peptide drug — animal-pituitary-derived ACTH, on the market since 1952, still used for infantile spasms and MS relapse. It's also the full-length hormone this site's Semax page traces its ACTH(4-10) fragment back to. The modern evidence for Acthar's expensive, on-patent uses is thinner than its age suggests, and its manufacturer's business practices around it produced two of the largest pharmaceutical enforcement settlements in recent US history.

In brief

Should you care? Yes if you've read this site's Semax page — Semax is a fragment, ACTH(4-10), of the same full-length hormone Acthar Gel actually is.

The short version

Approved since 1952 — one of the oldest peptide drugs still on the US market.
MS-relapse evidence includes one real small placebo-controlled trial and a larger, non-randomized comparative registry — a genuinely mixed picture, not settled.
A real $260 million DOJ settlement and $100 million FTC settlement against its manufacturer, over kickbacks, Medicaid rebates and blocking a competing drug.

What it is, and its real 1952 approval

Acthar Gel (repository corticotropin injection) is a mixture of ACTH analogs derived from porcine pituitary glands — a real, full-length version of adrenocorticotropic hormone, formulated to release slowly after injection. FDA approved it in 1952 for a broad list of corticosteroid-responsive conditions: rheumatic, collagen, dermatologic, allergic, ophthalmic, respiratory and edematous states. An indication for acute MS relapse was added later. It has stayed on the US market, under different manufacturers (most recently Mallinckrodt), for over 70 years.

The MS-relapse evidence, specifically

The clearest randomized evidence for MS relapse is the OPTIONS trial, a Phase 4, placebo-controlled study in adults with relapsing-remitting MS who had already failed high-dose corticosteroids; participants given Acthar Gel showed greater improvement in disability scores than placebo. A separate, larger, non-randomized observational registry study (PMID 33414758) reported Acthar resolving relapses in a substantially higher share of cases than IV methylprednisolone, IVIG, or plasmapheresis — a striking comparison, but an observational one, vulnerable to confounding by indication (sicker or steroid-refractory patients may have been selected differently across arms), not a head-to-head randomized trial.

Infantile spasms: a real, more recent approval

FDA approved Acthar Gel as monotherapy for infantile spasms in infants and children under 2 in October 2010, after its advisory committee voted 22-1 (one abstention) that the manufacturer had shown substantial evidence of effectiveness. This is a real, comparatively modern, committee-reviewed approval for a serious pediatric epilepsy syndrome with few other options.

A real, serious enforcement record

In 2022, Mallinckrodt agreed to pay $260 million to settle DOJ allegations that it knowingly underpaid Medicaid drug rebates for Acthar — by claiming, starting in 2013, that Acthar was a "new drug" first marketed that year rather than one approved since 1952 — and used a charitable foundation (the Chronic Disease Fund, now Good Days) as a conduit to pay illegal co-pay kickbacks. Separately, Questcor (Mallinckrodt's predecessor) paid the FTC $100 million to settle allegations it illegally acquired the rights to a competing drug, Synacthen Depot, specifically to preserve Acthar's monopoly. These are real, adjudicated federal enforcement actions, not allegations we're relaying secondhand.

A real, serious regulatory-enforcement chapter

None of this means Acthar doesn't work for anything — the infantile-spasms approval and the OPTIONS trial are real, controlled evidence. But the price and marketing history around Acthar's broader, older indications is itself part of the honest story: a 70-year-old drug whose original-era evidence for many of its listed uses is thin by modern standards, priced at a multiple of a thousand times its historical cost, defended in part through conduct two separate federal agencies found unlawful.

References

FDA approval history, H.P. Acthar Gel (repository corticotropin injection): initial approval 1952; MS relapse indication added later.
FDA approval of Acthar Gel for infantile spasms monotherapy, October 2010, following a 22-1 (1 abstention) advisory committee vote.
"A Prospective Observational Registry of Repository Corticotropin Injection (Acthar Gel) for the Treatment of Multiple Sclerosis Relapse," PMID 33414758 — observational, non-randomized design.
US Department of Justice, "Mallinckrodt Agrees to Pay $260 Million to Settle Lawsuits Alleging Underpayments of Medicaid Drug Rebates and Payment of Illegal Kickbacks," 2022; FTC $100 million Synacthen Depot settlement.