pirfenidone / Generic mfg. - LARVOL DELTA

The emerging role of pancreatic exocrine fibrosis as a common aetiological driver of islet dysfunction and diabetes: opportunities for novel disease-modifying interventions. (PubMed, Diabetologia) - "The antifibrotic agents pirfenidone and nintedanib, thought to work primarily through suppression of TGF-β function, are used routinely in clinical practice for non-pancreatic indications, with a first trial in pancreatitis underway. Trials evaluating these licensed therapeutics that include primary diabetes-related endpoints and measures aiming to elucidate the underlying mechanisms of action merit consideration in type 3c diabetes and ultimately in type 2 diabetes and in combinatorial regimens in type 1 diabetes."

Journal • Review • Cystic Fibrosis • Diabetes • Fibrosis • Genetic Disorders • Immunology • Metabolic Disorders • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Pancreatitis • Pulmonary Disease • Respiratory Diseases • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus • TGFB1

Management of Progressive Disease in Idiopathic Pulmonary Fibrosis (clinicaltrials.gov) - P4 | N=279 | Completed | Sponsor: Hospices Civils de Lyon | Recruiting ➔ Completed

Trial completion • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Isoforskolin inhibits LUBAC/GSDMD/IL-1β cascades in pulmonary fibrosis. (PubMed, J Thorac Dis) - "ISOF (0.5 and 1.0 µmol/L) was administrated as treatment drug in cell model, while pirfenidone (PFD; 10 µmol/L) and dexamethasone (DXM; 25 µmol/L) were administrated as control drug...The PF model of mice was established by intratracheal instillation of bleomycin (BLM)...In addition, ISOF may ameliorate PF by inhibiting the LUBAC/GSDMD/IL-1β cascades. Accordingly, LUBAC may be a potential therapeutic target for PF."

Journal • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • Targeted Protein Degradation • GSDMD • IL1B • TGFB1

Pirfenidone ameliorates dexamethasone-induced steatohepatitis and vascular resistance in rats. (PubMed, Life Sci) - "PFD may provide hepato- and vasculo-protective effects via its insulin-sensitization, hypoglycemic, hypolipidemic, antioxidant and anti-inflammatory activities."

Journal • Preclinical • Hepatology • CD34 • NFKB1 • NOS3

Hydronidone Capsules in the Treatment of Radiation-induced Lung Injury With or Without Immune Pneumonia (clinicaltrials.gov) - P2/3 | N=298 | Not yet recruiting | Sponsor: Beijing Continent Pharmaceutical Co, Ltd.

New P2/3 trial • Infectious Disease • Pneumonia • Respiratory Diseases

"Beyond Corticosteroids: A Systematic Review and Meta-analysis of Novel Therapies for Hypersensitivity Pneumonitis". (PubMed, Respir Med) - "Due to heterogeneity and limited high-quality evidence, definitive conclusions about novel therapies in HP remain elusive. However, rituximab and MMF showed promising results. Long-term randomized trials with standardized endpoints are needed to guide therapeutic decisions."

Journal • Retrospective data • Fibrosis • Immunology • Inflammation • Interstitial Lung Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases

"FIBR-MET-PF": Fibrosis-Modulating Effects of Metformin and Pirfenidone in Oral Submucous Fibrosis (clinicaltrials.gov) - P1/2 | N=45 | Completed | Sponsor: Ziauddin University | Recruiting ➔ Completed

Trial completion • Fibrosis • Immunology

Collagen depletion by pirfenidone enhances antitumor effect of oncolytic adenovirus against peritoneal metastases of gastric cancer. (PubMed, Mol Ther Oncol) - "Cancer-associated fibroblasts (CAFs) play a crucial role in collagen accumulation, which develops and promotes peritoneal metastasis (PM) in gastric cancer (GC). PFD suppressed collagen production in PM and improved viral penetration into the tumors, which enhanced the antitumor effects of OBP-702 against PM of GC. Collagen depletion by PFD enhances the penetration of OBP-702 into PM of GC, in turn enhancing the antitumor effects of OBP-702 against PM of GC."

IO biomarker • Journal • Gastric Cancer • Oncology • Solid Tumor • CAFs

A randomized, controlled, phase II clinical study on the prophylactic use of pirfenidone capsules to reduce the incidence of capsular contracture after breast reconstruction and radiotherapy in breast cancer patients (ChiCTR) - P2 | N=154 | Not yet recruiting | Sponsor: Zhejiang Cancer Hospital; Zhejiang Cancer Hospital

New P2 trial • Breast Cancer • Oncology • Solid Tumor

Pirfenidone as a Pleiotropic Antifibrotic Agent in Metabolic Steatohepatitis: From Mechanisms to Clinical Evidence. (PubMed, Arch Med Res) - "These data suggest that pirfenidone acts on central fibrogenic biology and may contribute to histological regression in advanced disease. Larger and longer trials, as well as rational combinations with metabolic agents, are needed to define its therapeutic role in MASH."

Journal • Review • Fibrosis • Hepatology • Idiopathic Pulmonary Fibrosis • Immunology • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Pulmonary Disease • Respiratory Diseases • TGFB1

‌Clinical Observation of Oral Pirfenidone in the Treatment of Stiff skin syndrome (ChiCTR) - P=N/A | N=10 | Not yet recruiting | Sponsor: Beijing Childrens Hospital,Capital Medical University; Beijing Childrens Hospital,Capital Medical University

New trial

PlatinumIV Complex Enabling Multiple and Potent Tumor Microenvironment Remodeling for Cancer Chemo-Immunotherapy. (PubMed, J Med Chem) - "Herein, we report novel platinumIV prodrugs that integrate two clinically approved drugs with different but complementary mechanisms, where cisplatin provides tumor cytotoxicity while the pirfenidone analogue contributes to tumor microenvironment modulation. Notably, they triggered the release of damage-associated molecular patterns (DAMPs), promoted dendritic cell maturation, and induced strong immunogenic cell death despite that cisplatin is unable to induce an immunological response. In vivo studies further confirmed their antitumor activity (3.3-fold tumor inhibition compared to cisplatin) and favorable safety profile (64% weight loss by cisplatin, none with platinumIV complexes)."

Biomarker • IO biomarker • Journal • Oncology

Combination of Atezolizumab and Pirfenidone in Second-line and Beyond NSCLC (clinicaltrials.gov) - P1/2 | N=25 | Recruiting | Sponsor: University of Kansas Medical Center | Trial primary completion date: Apr 2024 ➔ Jan 2027

Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • ROS1

Efficacy and Safety of Pirfenidone in Patients with Progressive Pulmonary Fibrosis: A Retrospective Single-Center Study. (PubMed, Life (Basel)) - "The international guidelines recommended the use of nintedanib for PPF, while evidence supporting pirfenidone remains insufficient. All adverse events related to pirfenidone were mild. In conclusion, the use of pirfenidone in PPF can potentially reduce the rate of FVC decline in real clinical practice."

Journal • Retrospective data • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Inflammatory Arthritis • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology

Idiopathic Pulmonary Fibrosis: A Comprehensive Review of Risk Factors, Genetics, Diagnosis, and Therapeutic Approaches. (PubMed, Biomedicines) - "While antifibrotic therapies (Pirfenidone and Nintedanib) have revolutionized management by slowing the decline in lung function, the therapeutic landscape continues to evolve. Ongoing research efforts are focused on integrating clinical, radiological, genetic, and biomarker data to facilitate early diagnosis and develop personalized treatment strategies to improve patient outcomes."

Journal • Review • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • MMP7 • MUC5B

Magnesium, Zinc and Copper in Lung Fibrosis: A Narrative Review. (PubMed, Medicina (Kaunas)) - "There are no randomized clinical trials yet, but some clinical and experimental results suggest that the association of zinc and magnesium with pirfenidone and nintedanib could be beneficial and should be assessed as soon as possible after the onset of this disease. The correction of hypomagnesemia and hypozincemia, whenever they exist, must be performed as soon as possible after the diagnosis of fibrosis."

Clinical • Journal • Review • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • SIRT1

The Mechanism of Oxidative Stress in Pulmonary Fibrosis and Research Progress. (PubMed, Antioxidants (Basel)) - "Currently, the only two clinically approved therapeutic drugs (nintedanib and pirfenidone) can only partially slow disease progression without reversing fibrotic lesions, and are associated with varying degrees of adverse effects. We also specifically highlight the latest progress and challenges in therapeutic strategies targeting oxidative stress, and discuss next-generation therapies, including the modulation of endogenous antioxidant pathways, supplementation of exogenous antioxidants, as well as nanomaterials, exosomes, and combination therapies. We hope this review will deepen the understanding of oxidative stress and pulmonary fibrosis, and provide new directions for improving the clinical efficacy of oxidative stress-targeted therapies."

Journal • Review • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Comparison of the Efficacy of Pirfenidone and Nintedanib in the Treatment of Patients with Idiopathic Pulmonary Fibrosis-A Single-Center Experience. (PubMed, Medicina (Kaunas)) - "The absence of significant differences in functional decline, progression rates, and survival indicates that treatment choices should be guided by individual clinical profiles rather than efficacy alone, reinforcing antifibrotic therapy as the primary approach to alter the course of IPF. Importantly, disease progression was strongly associated with a probable UIP pattern on HRCT, supporting current guidelines suggesting that probable UIP has a natural history and prognosis similar to those of definite UIP."

Journal • Idiopathic Pulmonary Fibrosis • Immunology • Infectious Disease • Interstitial Lung Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases

Impact of Pirfenidone on Arrhythmic and Clinical Outcomes in Patients With Idiopathic Pulmonary Fibrosis. (PubMed, J Cardiovasc Electrophysiol) - "Pirfenidone use to treat IPF was associated with fewer arrhythmic events and less diastolic dysfunction compared to patients who did not use pirfenidone during long-term follow-up. Additionally, obesity is associated with a higher incidence of arrhythmic events in patients with IPF."

Clinical data • Journal • Atrial Fibrillation • Cardiovascular • Coronary Artery Disease • Fibrosis • Genetic Disorders • Heart Failure • Hypertension • Idiopathic Pulmonary Fibrosis • Immunology • Obesity • Pulmonary Disease • Respiratory Diseases

Study of Oral Epigallocatechin-3-gallate (EGCG) in IPF Patients (clinicaltrials.gov) - P1 | N=50 | Active, not recruiting | Sponsor: Hal Chapman | Recruiting ➔ Active, not recruiting

Biomarker • Enrollment closed • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • POSTN

Pterostilbene ameliorates pulmonary fibrogenesis and inflammation targeting IL-23/ATP6V0D2 pathway: remodel local microenvironment of alveolar epithelial cells and fibroblasts. (PubMed, Int Immunopharmacol) - "TGF-β-stimulated BEAS-2B or primary lung fibroblasts (LFs) were cultured with PTE or pirfenidone (PFD). Mice were received intratracheal instillation of bleomycin (BLM) and administered PTE or PFD...PTE also inhibited fibrogenesis, EMT, and inflammation in activated-primary LFs and blocked CM-triggered primary LFs activation by regulating IL-23-ATP6V0D2 axis. In conclusion, PTE ameliorated pulmonary fibrosis targeting IL-23/ATP6V0D2 pathway, especially remodeling the local microenvironment of alveolar epithelial cells and fibroblasts, which might be a novel therapeutic strategy against pulmonary fibrosis."

Journal • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • IL1B • IL23A • TGFB1 • VIM

Predictors of Disease Progression in Idiopathic Pulmonary Fibrosis Under Antifibrotic Therapy: A Retrospective Study. (PubMed, Cureus) - "Lower %PEF and %TLC may predict poorer response to antifibrotics in IPF. These readily available PFT indices could serve as practical markers for risk stratification and early intervention. Prospective, multicenter studies are warranted to confirm predictive value."

Journal • Retrospective data • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Infectious Disease • Interstitial Lung Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases

Advances in the research and application of stem cell therapies for idiopathic pulmonary fibrosis. (PubMed, Am J Clin Exp Immunol) - "Current treatments, such as pirfenidone and nintedanib, slow disease progression but do not halt it and are associated with side effects. Bioengineering advancements, including hydrogel scaffolds and 3D lung organoids, enhance stem cell retention and provide platforms for IPF research and drug screening. This review explores the therapeutic potential of stem cell therapies in IPF, integrating recent bioengineering developments and clinical prospects."

Journal • Review • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • Transplantation • CXCR4 • IL10 • TGFB1

Treatment Adherence and Persistence of Anti-Fibrotic Drugs in Real Life in Greece. (PubMed, Adv Respir Med) - "We have generated novel data concerning the factors that affect patients' outcomes under anti-fibrotic therapy. These findings may provide helpful insights for the therapeutic management of ILDs."

Journal • Retrospective data • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases

The role of free-fatty acid receptors FFA1 and FFA4 in organ fibrosis. (PubMed, Br J Pharmacol) - "Despite its clinical significance, antifibrotic therapy remains largely limited to pirfenidone and nintedanib for PF and resmetirom for MASH. Although these FFAR have been extensively investigated in the context of metabolic disorders, emerging evidence indicates that FFA1 and FFA4 also play critical roles in the pathophysiology of fibrosis across multiple organs. This review highlights the roles of FFA1 and FFA4 in mitigating fibrosis, either directly or indirectly, across various organs, including the liver, kidney, lung, heart, and peritoneum, as well as in disorders associated with fibrosis-related injuries."

Journal • Review • Chronic Kidney Disease • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Hepatology • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Inflammatory Bowel Disease • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Nephrology • Pulmonary Disease • Renal Disease • Respiratory Diseases • Scleroderma • Systemic Sclerosis