Mallinckrodt Pharmaceuticals is an American-Irish domiciled manufacturer of specialty pharmaceuticals (namely, adrenocorticotropic hormone), generic drugs and imaging agents. In 2017 it generated 90% of its sales from the U.S. healthcare system. While Mallinckrodt is headquartered in Ireland for tax purposes, its operational headquarters are in the U.S. Mallinckrodt's 2013 tax inversion to Ireland drew controversy when it was shown Acthar was Medicaid's most expensive drug.Mallinckrodt acquires (for repricing), manufactures, and distributes products used in diagnostic procedures and in the treatment of pain and related conditions. This includes the acquisition, manufacture, and distribution of specialty pharmaceuticals, active pharmaceutical ingredients, contrast products, and radiopharmaceuticals. The company employed 5,500 and had net sales of $3.2 billion in 2017; of which $2.9 billion was from the U.S. healthcare system.The company has been implicated as a major contributor to the prescription opioid scandal around the over-prescription of oxycodone in the United States.S.S.S.S.S.S.S.S.S.
Real-world data on evolving treatment patterns of Acthar Gel, a Food and Drug Administration-approved therapy for patients with symptomatic sarcoidosis, have remained limited. This study described the characteristics of patients with symptomatic sarcoidosis treated with Acthar Gel, medication utilization patterns, and physicians’ assessments of the effects of Acthar Gel on patients’ health status. A prospectively designed medical chart review study with a predefined protocol and analysis plan was conducted in November 2024, with data abstracted from patient records between April 2022 and November 2024. Eligible patients were aged ≥ 18 years, had symptomatic sarcoidosis, and had received Acthar Gel within ≤ 24 months. On average, patients with symptomatic sarcoidosis were 47 years old; most were men (56
Persistent pruritus (itch) affects the quality of life, and many itch syndromes remain untreatable. Previously, we identified the gastrin-releasing peptide receptor (GRPR) playing a critical role in mediating histamine-independent itch signaling. In this study, we aimed to identify small-molecule GRPR antagonists to treat histamine-independent itch. Starting with the known small-molecule GRPR antagonist PD 176,252, we conducted systematical structure-activity relationship studies. This effort led to the discovery of antagonists that exhibit up to an 11-fold increase in binding affinity compared to PD 176,252. Compound 45 (MP-4222), a GRPR antagonist with a four-fold increased binding affinity and equal selectivity over the neuromedin B receptor (NMBR), significantly inhibited itch behavior in the chloroquine (CQ)-induced acute itch mouse model. Additionally, we attempted to reconcile the discrepancy between our in vitro experimental data and the computational docking outcome using the recently reported GRPR-PD176252 cryo-EM structure. Our studies also suggested several potential modifications to improve potency, as well as identified functional groups that have the potential in radiolabeling for targeted GRPR imaging.
Aim: To examine the characteristics, treatment patterns, and physicians' assessments of outcomes for patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or dermatomyositis/polymyositis (DM/PM) who received Acthar Gel. Materials & methods: This survey-based medical chart review study asked rheumatologists who met specific inclusion criteria to abstract data from patient records covering the period from April 2022 to November 2024. Eligible patients were adults ≥18 years diagnosed with RA, SLE, or DM/PM, treated with Acthar Gel for ≤24 months. An online questionnaire screened and identified contributing physicians and collected anonymized patient data (baseline demographic, medical history, concomitant medications, Acthar Gel treatment history, and physicians' assessment of health status, symptom severity, treatment outcomes with Acthar Gel). Results: The study population comprised 73 patients with RA (average age 50 years; 49 [67%] female; 44 [60%] White/non-Hispanic), 56 with SLE (average age 42 years; 47 [84%] female; 28 [50%] African-American), and 104 with DM/PM (average age 52 years; 69 [66%] female; 62 [60%] White/non-Hispanic). Patients had received Acthar Gel for an average of 9 (RA) or 8 months (SLE, DM/PM), with most receiving treatment at the time of the study. Per physicians' assessment, health status improved in 68 (93%) patients with RA, 50 (89%) patients with SLE, and 100 (96%) patients with DM/PM after starting treatment with Acthar Gel. 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. Conclusion: These findings support the use of Acthar Gel as a potential treatment option for appropriate patients with RA, SLE, or DM/PM.
Aim: Proteinuria poses a significant challenge in focal segmental glomerulosclerosis (FSGS), particularly when resistant to standard treatments. Acthar R Gel, a Food and Drug Administration (FDA)-approved treatment, may be a potential option for proteinuria in nephrotic syndrome (NS) due to FSGS, particularly given the limited alternative therapies. This study assessed the cost-per-response of Acthar Gel versus standard of care (SoC) for the treatment of refractory proteinuria in NS due to FSGS among adults from a US healthcare payer perspective over a 1- to 3-year horizon. Materials & methods: A probabilistic, cohort-based state-transition model tracked adults with nephrotic-range proteinuria due to FSGS through clinically relevant health states in 6-month cycles. All patients entered in relapse and received either Acthar Gel or SoC. At each cycle, individuals could transition to response or remain uncontrolled, progress to renal failure, or continue in relapse; death was permitted from any state. Responders were allowed to either sustain response or experience relapse in subsequent cycles. Model inputs for clinical event rates, healthcare utilization and medical costs were sourced from the published literature, and drug costs were valued using wholesale acquisition cost. Cost-per-response was defined as total healthcare costs (drug and nondrug medical costs) per patient divided by the response rate. Results: Acthar Gel showed a lower costper- response ($469,735) versus cyclophosphamide ($2,140,400) and rituximab ($1,272,477) over 1 year. This advantage for Acthar Gel was sustained for 2 and 3 years. Acthar Gel was potentially a dominant treatment option at 2 and 3 years, with a lower overall cost of care and higher response rates than SoC. Conclusion: 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.
INTRODUCTION:Evidence on the comparative real-world effectiveness of terlipressin vs midodrine plus octreotide (MO) for hepatorenal syndrome-acute kidney injury (HRS-AKI) in the United Kingdom and the United States is limited. METHODS:Using individual-level chart review data for patients across the United Kingdom (2013-2017) and the United States (2016-2019), an indirect treatment comparison was conducted comparing the efficacy of terlipressin (UK cohort) with MO (US cohort). Covariate balancing propensity scoring matched the cohorts on baseline serum creatinine (SCr), presence of encephalopathy and/or ascites, albumin use and duration, age, and sex. The primary endpoint was HRS reversal, defined as achieving SCr ≤1.5 mg/dL by the last day of treatment. RESULTS:At treatment initiation, 90.2% of UK patients received terlipressin (194/215), while 89.2% of US patients received MO (140/157). Concomitant albumin was administered in 67.9% of UK and 98.7% of US patients. In a covariate balancing propensity score-adjusted cohort, HRS reversal was achieved in 53.2% of terlipressin-treated patients (the United Kingdom, weighted effective sample size of 75) compared with 16.9% of MO-treated patients (the United States, n = 89) (adjusted mean difference (95% CI) 36.3% (22.4, 50.2), P < 0.0001). In adjusted analysis, individuals treated with terlipressin experienced an overall reduction in SCr at completion of treatment (SCr decrease 1.00 mg/dL vs increase of 0.08 mg/dL for MO-treated patients, P < 0.0001). DISCUSSION:HRS-AKI treatment and outcomes differ between the United Kingdom and the United States, attributed to the historical standard of care MO in the United States. In adjusted analyses, real-world use of terlipressin was more effective than MO at improving kidney function and achieving HRS-AKI reversal.
