H.P. Acthar Gel (repository corticotropin injection) / Mallinckrodt - LARVOL DELTA

Corticotropin for Behçet's Disease: A Multicenter Randomized Controlled TrialAcronym. (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Peking University People's Hospital

New P2 trial

New insights into scleritis: comprehensive analysis of demographics, clinical features, treatment approaches, and complications in a Northern California tertiary referral center (ARVO 2025) - "Biologics (19.09%) included adalimumab (7.47%), rituximab (5.67%), and infliximab (2.58%). Other treatments included repository corticotropin injection (2.93%) and local steroids (e.g., dexamethasone or triamcinolone) (1.71%)...Eye specialists were pivotal in managing these cases, often prescribing complex treatments typically associated with rheumatology. Despite potential complications like cataracts and glaucoma, many patients experienced improved outcomes with modern therapies.This research underscores the importance of specialized care and advanced treatments in managing scleritis, highlighting promising strategies to reduce vision loss and improve quality of life for those with this challenging condition."

Clinical • Cataract • Glaucoma • Ocular Inflammation • Ophthalmology • Scleritis • Uveitis

Efficacy and tolerability of subcutaneous repository corticotropin injection in ocular inflammation (ARVO 2023) - "Concomitant IMTs included mycophenolate mofetil (23.5%) and methotrexate (23.5%) along with biologics such as adalimumab (23.5%). Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Clinical • Ocular Inflammation • Ophthalmology • Scleritis • Uveitis

Real-world 6-month outcomes of repository corticotropin injection in noninfectious posterior uveitis unresponsive to immunomodulatory therapy (ARVO 2025) - "Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Clinical • Immunomodulating • Real-world • Real-world evidence • Ocular Inflammation • Ophthalmology • Uveitis

Long-term efficacy and tolerability of subcutaneous repository corticotropin injection in patients with ocular inflammatory diseases (ARVO 2025) - "Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Clinical • Ocular Inflammation • Ophthalmology • Scleritis • Uveitis

Updated ocular pharmacology for noninfectious Uveitis: a comprehensive expert review. (PubMed, Expert Opin Pharmacother) - "Steroid-sparing approaches are discussed, including conventional immunomodulatory therapy, biologic agents such as tumor necrosis factor-α inhibitors, repository corticotropin injection, and emerging small-molecule therapies. The next decade of uveitis management will prioritize precision pharmacology aimed at sustained inflammation control while minimizing corticosteroid-associated toxicity. Advances in molecular targeting, novel sustained-release delivery systems, earlier biologic intervention, and improved diagnostic and imaging technologies will further enable individualized, mechanism-driven therapy."

Journal • Review • Inflammation • Ocular Inflammation • Oncology • Ophthalmology • Uveitis

Acthar Gel treatment in patients with rheumatoid arthritis, systemic lupus erythematosus, or dermatomyositis/polymyositis: analysis of physician-reported charts. (PubMed, J Comp Eff Res) - "The most common treatment goals achieved in patients with improved overall health status were improved overall symptoms, pain, physical function, and corticosteroid use in the RA cohort; overall symptoms, pain, corticosteroid use, and fatigue in the SLE cohort; and overall symptoms, strength, physical function, and corticosteroid use in the DM/PM cohort. These findings support the use of Acthar Gel as a potential treatment option for appropriate patients with RA, SLE, or DM/PM."

Journal • Dermatomyositis • Fatigue • Immunology • Inflammatory Arthritis • Lupus • Myositis • Pain • Rheumatoid Arthritis • Rheumatology • Systemic Lupus Erythematosus

Clinical Presentation of Membranous Nephropathy in Children (NKF-SCM 2026) - "CONCLUSION These cases demonstrate that alternative immunomodulatory therapies, such as rituximab and ACTH analogs, can induce sustained remission. Early recognition and individualized therapy are crucial for favorable long-term outcomes."

Clinical • Dyslipidemia • Glomerulonephritis • Hepatitis B • Hepatology • Human Immunodeficiency Virus • Immunology • Infectious Disease • Inflammation • Metabolic Disorders • Nephrology • Renal Disease

Use of CXCL9 as a Biomarker of Acthar Efficacy (clinicaltrials.gov) - P4 | N=2 | Terminated | Sponsor: University of California, San Francisco | N=14 ➔ 2 | Recruiting ➔ Terminated; sponsor closed study down

Biomarker • Enrollment change • Trial termination • Immunology • Sarcoidosis

Clinical Presentation of membranous nephropathy in Children: A single center experience. (PAS 2026) - "Hypercholesterolemia was observed in Patients 1 and 2; only Patient 1 required statin therapy and low-dose aspirin for thromboprophylaxis.Conclusion(s): Primary MN in adolescents, though rare, can present as isolated nephrotic syndrome with preserved renal function and negative serologies. Three adolescents (two females, one male), aged 16 and 17 years, presented with nephrotic-range proteinuria (4+), edema, and hypoalbuminemia (1.3-2.6 mg/dL). All had normal blood pressure and normal renal function, with unremarkable serum electrolytes, complement levels (C3 and C4), inflammatory markers (CRP, ESR), and hematologic profiles. Autoimmune and infectious serologies, including ANA, ASO, ANCA panel, RPR, HIV, Hepatitis B and C, and Quantiferon-TB, were negative."

Clinical • Dyslipidemia • Glomerulonephritis • Hepatitis B • Hepatology • Human Immunodeficiency Virus • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Lupus • Metabolic Disorders • Renal Disease • Systemic Lupus Erythematosus

Adherence to Acthar Gel (RCI) and Outcomes in Patients with Membranous Nephropathy: A Claims Database Analysis. (PubMed, Clinicoecon Outcomes Res) - "To describe real-world patient characteristics and outcomes after initiation of Acthar Gel (repository corticotropin injection, RCI) in the management of nephrotic syndrome (NS)...Despite similar baseline medical costs, all-cause ($131,306 vs $50,048) and NS-related costs ($111,743 vs $29,868) were noticeably higher at follow-up in the below-average adherence cohort than the above-average adherence cohort. This real-world study shows that greater adherence to RCI during treatment improves overall outcomes studied."

Journal • Glomerulonephritis • Nephrology • Renal Disease

Endocrine modulation of inflammation: the role of adrenocorticotropic hormone and cortisol. (PubMed, Endocr Pract) - "Adrenocorticotropic hormone (ACTH), via the hypothalamic-pituitary-adrenal axis and direct interaction with MCR2, stimulates both cortisol synthesis and mediates steroid-independent immunomodulation in extra-adrenal tissues. Recent preclinical studies of selective MCR agonists, including MCR1-targeted compounds like dersimelagon, highlight novel therapeutic possibilities for autoimmune and fibrotic disorders. Understanding the dual steroidogenic and non-steroidogenic actions of melanocortins provides a framework for developing targeted therapies with improved safety profiles compared with conventional glucocorticoids."

Journal • Review • Fibrosis • Immunology • Inflammation • POMC-null Obesity

Use of Acthar in Rheumatoid Arthritis (RA) Related Flares (clinicaltrials.gov) - P4 | N=40 | Completed | Sponsor: Veena Ranganath, MD, MS | Recruiting ➔ Completed | Trial completion date: Dec 2025 ➔ May 2025 | Trial primary completion date: Dec 2025 ➔ May 2025

Trial completion • Trial completion date • Trial primary completion date • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

Symptomatic Sarcoidosis Treated with Acthar® Gel: Insights from a Physician-Reported Chart Review. (PubMed, Pulm Ther) - "Based on this chart review, Acthar Gel may represent a potential treatment option for selected patients with symptomatic sarcoidosis. In this study, among patients with symptomatic sarcoidosis treated with Acthar Gel, physicians documented reduced overall symptoms, improved physical function, decreased pain, improved fatigue, reduced corticosteroid use, improved lung functioning, and improved strength using prespecified assessments."

Journal • Cardiovascular • Fatigue • Hypertension • Immunology • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Osteoarthritis • Pain • Rheumatology • Sarcoidosis

Acthar Gel versus standard of care for adults with proteinuria in nephrotic syndrome due to focal segmental glomerulosclerosis: cost-per-response analysis from the US healthcare perspective. (PubMed, J Comp Eff Res) - " Acthar Gel showed a lower cost-per-response ($469,735) versus cyclophosphamide ($2,140,400) and rituximab ($1,272,477) over 1 year... From a US healthcare payer perspective, Acthar Gel appears to be a cost-effective, value-based treatment option for adults with proteinuria in NS due to FSGS over 1 to 3 years. These findings may aid providers and payers in making informed treatment decisions when conventional therapies are ineffective for these patients."

Journal • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Nephrology • Renal Disease

Use of repository corticotropin injection for the prophylaxis of corneal graft rejection in high-risk patients: A case series. (PubMed, Int J Surg Case Rep) - "The use of RCI prophylactically in high-risk, post-keratoplasty patients demonstrated maintenance or improvement in VA in the majority of patients. The results of this study also showed that RCI was safe and well tolerated, which is consistent with the known safety profile of RCI."

Journal • Review • Inflammation • Ophthalmology • Transplant Rejection • Transplantation

ACTH as A Re-emerging theRapy for Uveitis (The ACTHAR Study) (clinicaltrials.gov) - P2 | N=28 | Completed | Sponsor: Quan Dong Nguyen | Unknown status ➔ Completed

Trial completion • Ocular Inflammation • Ophthalmology • Uveitis

Repository Corticotropin Therapy for Refractory Noninfectious Inflammatory Ocular Diseases. (PubMed, J Clin Med) - "Relative risk analysis (RR) showed a 40.0% risk reduction for cystoid macular edema (RR = 0.60, p = 0.054). RCI may be an alternative treatment for refractory noninfectious ocular inflammatory diseases in patients who have failed treatment with corticosteroids."

Journal • Cataract • Immunology • Inflammation • Macular Edema • Ocular Inflammation • Ophthalmology • Scleritis • Uveitis

Melanocortin Therapy Mitigates Glomerular Complement Activation and Podocyte Injury in Membranous Nephropathy via MC5R Signaling (KIDNEY WEEK 2025) - "Mechanistically, glomerular fixation of C5b-9 and C3 was reduced with melanocortin therapy in diseased WT mice but increased by MC5R KO, despite similar glomerular deposition of the nephritogenic antibody and activation of C4, suggesting that MC5R signaling exerts an anti-complement effect primarily through mitigating C3 amplification. In consistency, unbiased transcriptomic analysis of the publicly available renal transcriptome data from ACTH- and vehicle-treated mice indicated a marked suppression of renal expression of CFB and CFD following ACTH treatment. Conclusion MC5R signaling intercepts the complement amplification loop in podocytes, thereby mitigating glomerular injury in experimental MN."

Glomerulonephritis • Renal Disease • CFB

Repository Corticotropin Injection Reduces Inflammation and Bone Turnover Markers in the Murine CIA Model (ACR Convergence 2025) - "As monotherapy, RCI significantly reduced CIA-induced joint swelling in male mice. In addition, RCI treatment resulted in a reduction in inflammatory cytokine responses, but no disruption of IgG formation and less bone loss. These findings demonstrate significant reductions in systemic inflammation in the CIA arthritis model with RCI treatment."

Preclinical • Immunology • Inflammation • Osteoporosis • Rheumatology • CXCL1 • IL6

Polymorphism of Melanocortin Receptor Genes-Association with Inflammatory Traits and Diseases. (PubMed, Diseases) - "Among them, α-MSH analogs play a role in atopic dermatitis and scleroderma, and MC1R agonist Dersimelagon has shown effectiveness in systemic sclerosis. The FDA has recently approved the repository corticotropin injection (RCI) to treat sarcoidosis. The FDA has also approved various melanocortin agonists, i.e., Bremelanotide, Afamelanotide, and Setmelanotide, for the treatment of hypoactive sexual desire disorder, Erythropoietic protoporphyria, and obesity, due to pro-opiomelanocortin and leptin receptor deficiency, respectively. Therefore, this review aims to summarize the function and genetic polymorphism of melanocortin receptors, regulatory pathways involving MCRs, and the existing evidence of the prime effect of MCRs on inflammatory responses via different mechanisms and their potential therapeutic use in inflammatory diseases."

Journal • Review • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • Atopic Dermatitis • CNS Disorders • Depression • Dermatitis • Dermatology • Diabetes • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Immunology • Inflammation • Inflammatory Bowel Disease • Major Depressive Disorder • Melanoma • Metabolic Disorders • Multiple Sclerosis • Obesity • Ocular Inflammation • Oncology • Ophthalmology • POMC-null Obesity • Psychiatry • Reperfusion Injury • Respiratory Diseases • Rheumatology • Sarcoidosis • Scleroderma • Sexual Disorders • Solid Tumor • Systemic Sclerosis • Type 2 Diabetes Mellitus • Uveitis • LEP • LEPR

Efficacy of Acthar gel and Tacrolimus in DNA-JB9 Positive Fibrillary Glomerulopathy. (PubMed, Kidney Int Rep) - "The addition of tacrolimus was not additive with ACTH in reducing proteinuria or stabilization of eGFR. Acthar gel is an effective antiproteinuric therapy for DNA-JB9 positive FGN."

Journal • Chronic Kidney Disease • Glomerulonephritis • Nephrology • Renal Disease

Treatment Patterns and Outcomes of Acthar Gel in Ankylosing Spondylitis and Psoriatic Arthritis: A Physician-Reported Chart Review. (PubMed, Open Access Rheumatol) - "Based on chart review, Acthar Gel may represent a potential treatment option for appropriate patients with AS or PsA. In this study, among patients with AS or PsA treated with Acthar Gel, physicians documented a reduction in overall symptoms, decreased pain, improved physical function, reduced corticosteroid use, improved strength, and improved fatigue using prespecified assessments."

Journal • Ankylosing Spondylitis • Back Pain • Cardiovascular • Fatigue • Hypertension • Immunology • Inflammatory Arthritis • Musculoskeletal Pain • Osteoarthritis • Pain • Psoriatic Arthritis • Rheumatology • Seronegative Spondyloarthropathies

Cost per Response of Acthar® Gel vs Standard of Care for the Treatment of Proteinuria in Nephrotic Syndrome Due to Idiopathic Membranous Nephropathy Among Adults from the US Healthcare Perspective. (PubMed, J Health Econ Outcomes Res) - "Objective: The cost per response of Acthar® Gel vs standard of care (SoC; cyclophosphamide or rituximab) for treatment of proteinuria in NS due to iMN was evaluated among adults who had failed multiple treatments from a US payer perspective over a 1- to 3-year horizon... Based on current model assumptions and clinical inputs, Acthar® Gel may potentially be a cost-effective and value-based treatment strategy vs unapproved SoCs for adults with refractory proteinuria in NS due to iMN, particularly for those who have not responded to conventional therapies over a 1- to 3-year period within a US payer context. These results may inform clinical and payer decision-making in cases when other standard therapies fail to achieve desired outcomes for a specific population."

Journal • Glomerulonephritis • Nephrology • Renal Disease

A Narrative Review of the Immunomodulatory Effects of Acthar® Gel Beyond Its Steroidogenic Properties. (PubMed, Adv Ther) - "Preclinical and clinical studies have shown that the immunomodulatory effects of Acthar Gel are distinct from those of corticosteroids and other adrenocorticotropic hormone (ACTH)-class therapeutics...Receptor binding initiates an intracellular signal transduction cascade that ultimately regulates the expression of anti-inflammatory genes. Collectively, the experimental and clinical studies reviewed here suggest that Acthar Gel acts as an immunomodulator via melanocortin receptors and may be an effective anti-inflammatory therapeutic option for patients with IMIDs who are refractory or intolerant to corticosteroids.Graphical Abstract available for this article."

Journal • Review • CNS Disorders • Epilepsy • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Multiple Sclerosis • Ocular Inflammation • Rheumatoid Arthritis • Rheumatology • Systemic Lupus Erythematosus