zinpentraxin alfa (RG6354) / Roche - LARVOL DELTA

Serum amyloid P (PTX2) attenuates hepatic fibrosis in mice by inhibiting the activation of fibrocytes and HSCs. (PubMed, Hepatol Commun) - "Since HSCs serve as a major source of collagen type I-producing myofibroblasts and fibrocytes stimulate fibrosis, hSAP may become part of the therapy of liver fibrosis of different etiologies."

Journal • Preclinical • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • PTPRC

Quantitative analysis of bone marrow fibrosis highlights heterogeneity in myelofibrosis and augments histological assessment: An Insight from a phase II clinical study of zinpentraxin alfa. (PubMed, Hemasphere) - No abstract available

Heterogeneity • Journal • P2 data • Fibrosis • Immunology • Myelofibrosis

Zinpentraxin Alfa for Idiopathic Pulmonary Fibrosis: The Randomized Phase III STARSCAPE Trial (ATS 2024) - "There is no abstract associated with this presentation."

Clinical • P3 data • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Zinpentraxin Alfa in Patients With Idiopathic Pulmonary Fibrosis: Results and Learnings From the Phase III STARSCAPE Trial (ATS 2024) - P3 | "0% treated with pirfenidone or nintedanib) received zinpentraxin alfa (n=330) or placebo (n=330); [Table footnote]. Zinpentraxin alpha did not reduce the rate of FVC decline in patients with IPF. The different efficacy outcome in Phase II versus III could be explained by outliers in FVC decline occurring in placebo patients in Phase II, which impacted the calculated mean values and consequently the comparison of zinpentraxin alfa versus placebo. Understanding how outliers should be analyzed and what learnings can be taken forward is crucial to inform future IPF trials."

Clinical • P3 data • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Comparative Pharmacokinetics and Safety Assessment of 1st- and 2nd-Generation Zinpentraxin Alfa Drug Products in Healthy Volunteers: A Randomized Crossover Study. (PubMed, Clin Pharmacol Drug Dev) - "The study was stopped after stage 1 as the gating criteria were met based on the result of the blinded IA. Safety profiles were similar for the 1st- and 2nd-generation drug products, and antidrug antibody (ADA) was not observed in this study."

Clinical • Journal • PK/PD data • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

STARSCAPE: A Study to Evaluate the Efficacy and Safety of Recombinant Human Pentraxin-2 (rhPTX-2; PRM-151) in Participants With Idiopathic Pulmonary Fibrosis (clinicaltrials.gov) - P3 | N=665 | Terminated | Sponsor: Hoffmann-La Roche | Completed ➔ Terminated; The study was terminated by Sponsor as the futility analysis outcome indicated that the study was unlikely to meet the predefined primary objective of the study. No new safety concerns were identified.

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

Zinpentraxin alfa comparable to placebo in idiopathic pulmonary fibrosis (Healio) - "'Although well tolerated, no clinical benefit of zinpentraxin alfa over placebo was observed in the STARSCAPE trial in patients with IPF,' Luca Richeldi, MD, PhD..."

Media quote

Zinpentraxin Alfa for Idiopathic Pulmonary Fibrosis: The Randomized Phase III STARSCAPE Trial. (PubMed, Am J Respir Crit Care Med) - P3 | "Zinpentraxin alfa treatment did not benefit patients with idiopathic pulmonary fibrosis over placebo. Learnings from this program may help improve decision-making around trials in idiopathic pulmonary fibrosis. Clinical trial registration available at www."

Journal • P3 data • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases

A randomized, double-blind study of zinpentraxin alfa in patients with myelofibrosis who were previously treated with or ineligible for ruxolitinib: Stage 2 of a phase II trial. (PubMed, Haematologica) - "Not available."

Clinical • Journal • P2 data • Myelofibrosis

Successful Development of Nonclinical Anti-Drug Antibody Assays to Support Zinpentraxin Alfa Reproductive Toxicology Studies. (PubMed, AAPS J) - "Here, we share the final development/validation data and the immunogenicity study results. Our work highlights the need for the evaluation of alternate assay formats when evaluating novel drug modalities."

Journal • Developmental Disorders

Novel Selective Quantification of Zinpentraxin Alfa Biotherapeutic in the Presence of Endogenous Isomer in Plasma Samples of Idiopathic Pulmonary Fibrosis Patients Using Immunoaffinity LC-MS. (PubMed, AAPS J) - "The preliminary results suggest that endogenous SAP levels remained largely constant in IPF patients throughout the treatment with zinpentraxin alfa. Our novel approach provides a general bioanalytical strategy to selectively quantify α2,3-sialylated glycoproteins in the presence of their corresponding α2,6-linked isomers."

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

Repeat-Dose and Embryo-Fetal Developmental Toxicity of Zinpentraxin Alfa. (PubMed, Reprod Toxicol) - "The disparate effects of zinpentraxin alfa on embryo-fetal development between the two species suggests a potential unknown biological function of PTX-2 in pregnancy in the rabbit, which may be relevant to humans. Our findings warrant the consideration for highly effective contraceptive measures to avoid pregnancy in patients enrolled in clinical studies with zinpentraxin alfa."

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

Zinpentraxin Alfa Reduces Myelofibrosis in a JAK2-V617F Mouse Model of Myeloproliferative Neoplasms (ASH 2023) - P2 | "ZPN has also been investigated as monotherapy and in combination with ruxolitinib (RUX) in a phase 2 clinical study in patients with myelofibrosis (NCT01981850; Verstovsek S et al, Haematologica 2023). ZPN treatment in a JAK2-V617F mouse model of MPN with myelofibrosis was well tolerated as monotherapy and in combination with RUX. A reduction in the grade of myelofibrosis was observed in all ZPN treatment groups. ZPN showed promising trends in reducing platelet and monocyte counts, while the decrease in hemoglobin by RUX was in part prevented in combination with ZPN."

Preclinical • Hematological Disorders • Immunology • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Transplantation • CALR • JAK2

Treatment of anemia in myelofibrosis: focusing on Novel Therapeutic Options. (PubMed, Expert Opin Investig Drugs) - "This review summarizes novel and promising treatments for anemia in myelofibrosis including transforming growth factor-β inhibitors luspatercept and KER-050, JAK inhibitors momelotinib, pacritinib, and jaktinib, BET inhibitors pelabresib and ABBV-744, antifibrotic PRM-151, BCL2/BCL-XL inhibitor navitoclax, and telomerase inhibitor imetelstat. Standard approaches to treat myelofibrosis-related anemia have limited efficacy and are associated with toxicity. New drugs have shown positive results in myelofibrosis-associated anemia when used alone or in combination."

Journal • Review • Anemia • Hematological Disorders • Immunology • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • BCL2 • BCL2L1

Quantitative Analysis of Bone Marrow Features Highlights Heterogeneity in Myelofibrosis Patients Treated with Zinpentraxin Alfa in a Phase II Clinical Study (ASH 2023) - P2 | "ZPN is a recombinant form of human pentraxin-2 (PTX2) that has shown clinical activity as monotherapy and in combination with ruxolitinib (RUX) in a phase II trial in patients with Int-1/-2 or high risk MF (NCT01981850). This likely reflects poorly understood and under-recognised variation in morphological features encountered in patients with longstanding and/or pre-treated MF when compared to newly diagnosed patients. This highlights the potential of such variability to confound the evaluation of novel therapeutics in MPN, and emphasises the utility of robust quantitative methods to analyse and visualise morphological features in clinical study samples that can complement conventional manual assessment."

Clinical • Heterogeneity • P2 data • Hematological Malignancies • Immunology • Leukemia • Myelofibrosis • Myeloproliferative Neoplasm • Oncology

Weak to no correlation between quantitative high-resolution computed tomography metrics and lung function change in fibrotic diseases. (PubMed, ERJ Open Res) - "This retrospective study used data from patients who were not treated with investigational drugs with and without background antifibrotic therapies in tocilizumab phase 3 SSc, lebrikizumab phase 2 IPF, and zinpentraxin alfa phase 2 IPF studies conducted from 2015 to 2021. The incremental prognostic value of the baseline HRCT metrics was marginal after adjusting baseline characteristics and was inconsistent across study arms. Data from the SSc and IPF studies suggested weak to no and inconsistent correlation between quantitative HRCT metrics derived by the Imbio LTA tool and FVC slope in the studied SSc and IPF population."

Journal • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • Scleroderma • Systemic Sclerosis

Evaluation of multiple immunoassay formats for detection of anti-drug antibodies to zinpentraxin alfa. (PubMed, J Immunol Methods) - "Overall, the semi-homogenous ADA assay format with no sample pre-treatment was selected for the measurement of zinpentraxin alpha immunogenicity as it provided the desired sensitivity, drug tolerance, and reproducibility. Our study emphasizes the importance of assay format evaluation during drug development and the necessity to select the most suitable assay format and sample pre-treatment method by which to evaluate therapeutic drug immunogenicity."

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

Development of a Cell-based Neutralizing Antibody Assay for Zinpentraxin Alfa: Challenges and Mitigation Strategies. (PubMed, AAPS J) - "We also demonstrated that appropriate acidic buffers were critical in sample pretreatment to improve assay drug tolerance, which not only dissociated the drug/NAb immune complex but also effectively and irreversibly denatured the free drug. The final assay performed well with confirmed assay robustness and suitability for the clinical applications."

Journal

Safety and efficacy of zinpentraxin alfa as monotherapy or in combination with ruxolitinib in myelofibrosis: stage I of a phase II trial. (PubMed, Haematologica) - P2 | "Overall, zinpentraxin alfa showed evidence of clinical activity and tolerable safety as monotherapy and in combination with ruxolitinib in this open-label, non-randomized trial. ClinicalTrials.gov Identifier: NCT01981850."

Combination therapy • Journal • Monotherapy • P2 data • Fatigue • Hematological Disorders • Immunology • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Thrombocytopenia

[VIRTUAL] New Therapies in Development for Myelofibrosis (SOHO 2020) - P1/2, P1b, P2, P3 | "Ruxolitinib blocks excessive proliferation of hematopoietic stem cells and pro-inflammatory cytokine production, which leads to improvement in quality-of-life and spleen volume, thus prolonging survival in MF patients.2 In late 2019, another oral JAK2 inhibitor, fedratinib, was approved for intermediate-2 and high-risk MF...Interim data from the trial demonstrated reduction in spleen volume, BM fibrosis, anemia and blood transfusions, as well as total symptom score improvement in MF patients who were JAK-inhibitor naive7 or had a suboptimal response to ruxolitinib.8 Notably, preclinical studies manifested synergistic lethal activity of combined HSP90 (a chaperone of JAK2) and BET inhibitors in ruxolitinib-resistant post-MPN AML cells,6 and combination treatment of MPN cells with the HSP90 inhibitor PU-H71 and ruxolitinib synergistically reduced p-JAK2 and inhibited the JAK/STAT pathway.9 On the basis of the aforementioned preclinical findings, a phase..."

IO biomarker • Myelofibrosis • Oncology • Polycythemia Vera • BCL2 • BCL2L1 • FLT3 • JAK3 • NFKB1

"Vabysmo becomes @Roche’s top growth product in Q1 2023, though there are R&D setbacks for Tecentriq and former Promedior drug PRM-151 https://t.co/qDqHbZWC4N" (@pharmaphorum)

STARSCAPE-OLE: A Study to Evaluate Long Term Safety and Efficacy of Recombinant Human Pentraxin-2 (rhPTX-2; PRM-151) in Participants With Idiopathic Pulmonary Fibrosis (clinicaltrials.gov) - P3 | N=117 | Terminated | Sponsor: Hoffmann-La Roche | Trial completion date: Dec 2028 ➔ Feb 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: Dec 2028 ➔ Feb 2023; The study was terminated by Sponsor as the futility analysis outcome indicated that the study was unlikely to meet the predefined primary objective of the study. No new safety concerns were identified.

Trial completion date • Trial primary completion date • Trial termination • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

STARSCAPE: A Study to Evaluate the Efficacy and Safety of Recombinant Human Pentraxin-2 (rhPTX-2; PRM-151) in Participants With Idiopathic Pulmonary Fibrosis (clinicaltrials.gov) - P3 | N=665 | Completed | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Completed

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

STARSCAPE: A Study to Evaluate the Efficacy and Safety of Recombinant Human Pentraxin-2 (rhPTX-2; PRM-151) in Participants With Idiopathic Pulmonary Fibrosis (clinicaltrials.gov) - P3 | N=665 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Dec 2023 ➔ Feb 2023 | Trial primary completion date: Dec 2023 ➔ Feb 2023 | Recruiting ➔ Active, not recruiting

Enrollment closed • Trial completion date • Trial primary completion date • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Roche Abandons AKT Prostate Cancer Asset (BioSpace) - "Roche is also punting its early-stage candidate efmarodocokin alfa, which was in a Phase I trial for acute graft-versus-host disease, zinpentraxin alfa, a candidate for idiopathic pulmonary fibrosis, and its Alzheimer’s hopeful, gantenerumab."

Discontinued • Acute Graft versus Host Disease • Alzheimer's Disease • Graft versus Host Disease • Idiopathic Pulmonary Fibrosis