Panhematin (hemin) / Lundbeck, Recordati - LARVOL DELTA

Acute Porphyria Biomarkers for Disease Activity (clinicaltrials.gov) - P=N/A | N=50 | Active, not recruiting | Sponsor: The University of Texas Medical Branch, Galveston | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Dec 2025 ➔ Dec 2026

Trial completion date • Trial primary completion date • Genetic Disorders • Hematological Disorders • Metabolic Disorders

Teaching an old drug new tricks: Regulatory insights for the repurposing of hemin in cardiovascular disease. (PubMed, Pharmacol Res Perspect) - "However, requirements for the pre-clinical and clinical characterization of biologics approved under the U.S. FDA's Orphan Drug Act in 1983 (such as hemin) differed significantly from current standards, presenting fundamental gaps in our collective understanding of hemin pharmacology as well as knowledge barriers to clinical translation for future applications. Using information extracted from the primary and regulatory literature (including documents submitted to Health Canada in support of hemin's approval for the Canadian market in 2018), we present a comprehensive case study of current knowledge related to hemin's biopharmaceutical properties, pre-clinical/clinical pharmacokinetics, pharmacodynamics, dosing, and safety, focusing specifically on the drug's effects on heme regulation and in the context of acute myocardial infarction."

Journal • Review • Cardiovascular • Congestive Heart Failure • Genetic Disorders • Heart Failure • Hematological Disorders • Metabolic Disorders • Myocardial Infarction

Panhematin for Prevention of Acute Attacks of Porphyria (clinicaltrials.gov) - P2 | N=13 | Terminated | Sponsor: The University of Texas Medical Branch, Galveston | N=20 ➔ 13 | Trial completion date: Jan 2025 ➔ Dec 2023 | Recruiting ➔ Terminated; Low accrual

Enrollment change • Trial completion date • Trial termination • Genetic Disorders • Hematological Disorders • Metabolic Disorders

Acute Porphyria Biomarkers for Disease Activity (clinicaltrials.gov) - P=N/A | N=50 | Active, not recruiting | Sponsor: The University of Texas Medical Branch, Galveston | Trial completion date: Dec 2023 ➔ Dec 2025 | Trial primary completion date: Dec 2023 ➔ Dec 2025

Biomarker • Trial completion date • Trial primary completion date • Genetic Disorders • Hematological Disorders • Metabolic Disorders

Controlled Trial of Panhematin in Treatment of Acute Attacks of Porphyria (clinicaltrials.gov) - P2 | N=25 | Completed | Sponsor: The University of Texas Medical Branch, Galveston | Active, not recruiting ➔ Completed | N=40 ➔ 25

Enrollment change • Trial completion • Genetic Disorders • Hematological Disorders • Metabolic Disorders • CPOX

Acute Porphyria Biomarkers for Disease Activity (clinicaltrials.gov) - P=N/A | N=50 | Active, not recruiting | Sponsor: The University of Texas Medical Branch, Galveston | Trial completion date: Sep 2023 ➔ Dec 2023 | Trial primary completion date: Sep 2022 ➔ Dec 2023

Biomarker • Trial completion date • Trial primary completion date • Genetic Disorders • Hematological Disorders • Metabolic Disorders

Panhematin for Prevention of Acute Attacks of Porphyria (clinicaltrials.gov) - P2 | N=20 | Recruiting | Sponsor: The University of Texas Medical Branch, Galveston | Trial completion date: Sep 2023 ➔ Jan 2025 | Trial primary completion date: Sep 2022 ➔ Jan 2024

Trial completion date • Trial primary completion date • Genetic Disorders • Hematological Disorders • Metabolic Disorders

Histone Deacetylase 6 Inhibition Prevents Vaso-Occlusion and Pain in Sickle Cell Mice (ASH 2022) - "To initiate VO, panhematin (3.2 µmole/kg) was infused via tail vein, and at 1-4 hours post-infusion venules were reexamined for stasis...Furthermore, HDAC6 inhibition prevented hemin-mediated pro-inflammatory microglial activation and reduced hemin-mediated acute pain stimulation. Collectively, these studies suggest that selective HDAC6 inhibition may be a strategy to reduce acute inflammation and pain in SCD."

Epigenetic controller • IO biomarker • Preclinical • Genetic Disorders • Hematological Disorders • Immunology • Inflammation • Pain • Sickle Cell Disease • IL6 • MYD88 • NLRP3 • SELP • VCAM1

Therapy Follows Diagnosis: Old and New Approaches for the Treatment of Acute Porphyrias, What We Know and What We Should Know. (PubMed, Diagnostics (Basel)) - "Recently, siRNA technology has been introduced in order to downregulate 5-ALA-synthase 1, which contributes to the patho-physiology of these diseases. Moreover, other novel therapies using enzyme protein replacement, mRNA techniques or proteostasis regulators are being developed."

Journal • Review • Genetic Disorders • Hematological Disorders • Metabolic Disorders

Cost savings with hemin versus givosiran for the treatment of patients with acute intermittent porphyria (AIP). (PubMed, J Med Econ) - "Hemin is expected to provide cost savings compared to givosiran for all AIP patients and subpopulations. Lower annual total costs of care with hemin range from $311,950 to $545,219 less depending on whether the patient uses hemin prophylactically or for acute treatment attacks."

Clinical • HEOR • Journal • Hepatology

Controlled Trial of Panhematin in Treatment of Acute Attacks of Porphyria (clinicaltrials.gov) - P2; N=40; Active, not recruiting; Sponsor: The University of Texas Medical Branch, Galveston; Trial completion date: Aug 2020 ➔ Aug 2023; Trial primary completion date: Aug 2020 ➔ Aug 2022

Clinical • Trial completion date • Trial primary completion date

Acute Porphyria Biomarkers for Disease Activity (clinicaltrials.gov) - P=N/A; N=50; Active, not recruiting; Sponsor: The University of Texas Medical Branch, Galveston; Trial completion date: Dec 2021 ➔ Sep 2023; Trial primary completion date: Dec 2020 ➔ Sep 2022

Biomarker • Trial completion date • Trial primary completion date

Circular exponential amplification of photoinduced electron transfer using hairpin probes, G-quadruplex DNAzyme and silver nanocluster-labeled DNA for ultrasensitive fluorometric determination of pathogenic bacteria. (PubMed, Mikrochim Acta) - "...Probe H2 contains an aptamer against hemin and is used to form the G-quadruplex DNAzyme in the presence of hemin and potassium ion...Strand displacement amplification leads to photoinduced electron transfer (PET) between G-quadruplex DNAzyme and DNA/AgNCs. HAP-based circular exponential amplification of PET results in an ultrasensitive fluorometric assay."

Journal • Biosimilar

DEVELOPING AN ALGORITHM TO IDENTIFY PATIENTS WITH ACUTE INTERMITTENT PORPHYRIA IN AN ADMINISTRATIVE CLAIMS DATABASE (ISPOR 2018) - "CONCLUSIONS : Identifying rare diseases using claims is challenging with non-specific diagnosis codes. This is the first claims-based algorithm to identify AHP patients using ICD-9-CM in combination with symptoms and urinalysis."

Clinical • Biosimilar • Cardiovascular • CNS Disorders • Hypertension • Pain

The Heme-Oxygenase 1 Induction Prevents Senescence in COPD Lung Fibroblasts by Protecting Against Mitochondrial Dysfunction (ATS 2018) - "...Therefore, we investigated if pharmacological induction of HO-1 by chronic hemin treatment prevents senescence and protects cells against defective mitophagy... HO-1 prevents senescence in COPD fibroblasts by protecting, at least in part, against mitochondria dysfunction and restoring mitophagy. Moreover, these results set up the basis for the development of new therapeutic strategies in COPD aimed to restore defective mitophagy."

Biosimilar • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

Pharmacological versus genetic inhibition of heme oxygenase-1 - the comparison of metalloporphyrins, shRNA and CRISPR/Cas9 system. (PubMed, Acta Biochim Pol) - "...Most of the clones harboring mutations within HMOX1 locus did not express HO-1 protein and failed to increase bilirubin concentration after hemin stimulation...In summary, we have shown that not all technologies can be used for inhibition of HO activity in vitro with the same efficiency. In our hands, the most potent and comprehensible results can be obtained using genetic tools, especially CRISPR/Cas9 approach."

Journal • Biosimilar • Oncology

Electrochemical detection of sequence-specific DNA based on formation of G-quadruplex-hemin through continuous hybridization chain reaction. (PubMed, Anal Chim Acta) - "Moreover, the established DNA sensor was challenged by detection of HIV DNA in human serum samples, which showed the low detection limit of 6.3 fM. Thus it has great application prospect in the field of clinical diagnosis and environmental monitoring."

Journal • Biosimilar • Gene Therapies • Genetic Disorders

Real world annualized healthcare utilization and expenditures among insured US patients with acute intermittent porphyria (AIP) treated with hemin. (PubMed, J Med Econ) - "For AIP patients treated with hemin, patients treated for acute attacks may use a greater number of resources compared to patients treated prophylactically."

Clinical • HEOR • Journal • Real-World Evidence

"This patient is progressing quickly, hopefully we will get her panhematin soon." (@F_Edrees)

Clinical

Panhematin for Prevention of Acute Attacks of Porphyria (clinicaltrials.gov) - P2; N=20; Recruiting; Sponsor: The University of Texas Medical Branch, Galveston; Trial completion date: Sep 2021 ➔ Sep 2023; Trial primary completion date: Sep 2020 ➔ Sep 2022

Clinical • Trial completion date • Trial primary completion date

Acute Porphyria Biomarkers for Disease Activity (clinicaltrials.gov) - P=N/A; N=50; Active, not recruiting; Sponsor: The University of Texas Medical Branch, Galveston; Enrolling by invitation ➔ Active, not recruiting

Biomarker • Enrollment closed

Controlled Trial of Panhematin in Treatment of Acute Attacks of Porphyria (clinicaltrials.gov) - P2; N=40; Active, not recruiting; Sponsor: The University of Texas Medical Branch, Galveston; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

Development of DNAzyme-based PCR signal cascade amplification for visual detection of Listeria monocytogenes in food. (PubMed, Anal Biochem) - "Through 20 pork samples assay, visual detection assay had the same results as conventional detection methods, and had a good performance. This is a powerful demonstration of the ability of G-quadruplex DNAzyme to be used for PCR-based assay with significant advantages of high sensitivity, low cost and simple manipulation over existing approaches and offers the opportunity for application in pathogen detection."

Journal

Microprocessor depends on hemin to recognize the apical loop of primary microRNA. (PubMed, Nucleic Acids Res) - "Furthermore, by generating a DGCR8 mutant cell line and carrying out rescue experiments, we discover that hemin preferentially stimulates the expression of miRNAs possessing the UGU motif, thereby conferring differential regulation of miRNA maturation. Our findings reveal the molecular action mechanism of hemin in pri-miRNA processing and establish a novel function of hemin in inducing specific RNA-protein interaction."

Journal

Murine bone marrow mesenchymal stromal cells respond efficiently to oxidative stress despite the low level of heme oxygenases 1 and 2. (PubMed, Antioxid Redox Signal) - "However, murine MSC Hmox1-/- do not differ from wild type MSCs in phenotype and functions. MSC Hmox1-/- show better resistance to hemin than fibroblasts and BDMCs and rapidly react to the stress by upregulation of quintessential genes in antioxidant response."

Journal