Pegasys (pegylated interferon α -2a) / Roche, Ascletis, Pharma& Schweiz - LARVOL DELTA

Bone marrow adipocytes (BMA) as a novel biomarker of molecular response in patients with essential thrombocythemia (ET) and polycythemia vera (PV) treated with pegylated interferon alfa-2A (ASH 2025) - "Treatment of MPN patients with IFN-α resulted in reproducible changes in BM cellularityincluding MK histo-topography, erythropoiesis, BMA number and distribution. Changes in BMA wereclosely associated with reduction in JAK2V617F VAF following PEG treatment."

Biomarker • Clinical • Essential Thrombocythemia • Hematological Disorders • Hematological Malignancies • Leukemia • Metabolic Disorders • Myeloproliferative Neoplasm • Obesity • Polycythemia Vera • Thrombocytosis • CALR • IFNA1 • STAT1

Persistent racial disparities in Sézary syndrome outcomes despite use of modern therapies: A single-center analysis (ASH 2025) - "With theincreasing use of modern systemic therapies (e.g., mogamulizumab, brentuximab vedotin, interferons,photopheresis) over the past decade, we sought to determine whether survival disparities by race persistin the current treatment era.MethodsWe retrospectively reviewed 75 patients with SS treated between January 2015 and June 2025 at MoffittCancer Center...Black patients were more likely toreceive ECP + Pegasys (69.2% vs. 26.8%), romidepsin (61.5% vs. 37.5%), brentuximab (38.5% vs. 14.3%),and combination chemotherapy (61.5% vs. 19.6%) compared to White patients, likely reflecting the moreaggressive nature of their disease.ConclusionOur cohort demonstrated better OS compared to historical studies, likely reflecting the impact of modernsystemic therapies and specialized care at a tertiary center...Black patients in our cohort had a markedly higher prevalence of large-celltransformation, earlier age at diagnosis, and more advanced clinical stage at presentation,..."

Clinical • Cutaneous T-cell Lymphoma • Dermatopathology • Hematological Malignancies • Lymphoma • Sezary Syndrome • T Cell Non-Hodgkin Lymphoma

Trial in progress: A phase I/ib dose-finding study of ropeginterferon alfa-2b (P1101) in patients with cutaneous T-cell lymphoma (CTCL) (ASH 2025) - P1 | "Whole blood, PBMC, and plasma samples will becollected at baseline, during therapy, and at progression. Gene expression and immune profiling willexplore predictors of response.This is the first prospective study of Ropeginterferon alfa-2b in CTCL in U.S. It aims to define a biologicallyactive, immunomodulatory dose with sufficient tolerability for extended administration."

Clinical • P1 data • Cutaneous T-cell Lymphoma • Dermatitis • Dermatology • Ewing Sarcoma • Immunology • Lymphoma • Mycosis Fungoides • Non-Hodgkin’s Lymphoma • Ocular Infections • Ophthalmology • Polycythemia Vera • Skin Cancer • T Cell Non-Hodgkin Lymphoma • IFNA1

P159 Use of Besremi® (pegylated interferon-alfa-2b) in the treatment of cutaneous T-cell lymphoma. (PubMed, Br J Dermatol) - "Four patients moved from Pegasys directly to other therapies due to disease progression or lack of control (two brentuximab, one bexarotene and one total skin electron beam)...However, we highlight that palpitations are reported as a common side-effect of Besremi in the product literature. We report ongoing results from the use of Besremi in MF/SS, discussing dosing, efficacy, safety and monitoring."

Journal • Cough • Cutaneous T-cell Lymphoma • Dermatology • Hematological Malignancies • Lymphoma • Mycosis Fungoides • Myeloproliferative Neoplasm • Oncology • Respiratory Diseases • Sezary Syndrome • T Cell Non-Hodgkin Lymphoma

Prospective Ropeginterferon Alfa-2b Therapy in PV & ET Influences Prothrombotic, Inflammatory and Hypoxia Inducible Factors Activities and Effect of Concomitant DNMT3A Mutation (ASH 2024) - "Ropeg starts as de novo treatment or after hydroxyurea (HU), Pegasys, and ruxolitinib...In our cohorts, 7 pts had concomitant DNMT3A; pt#1 could not tolerate Ropeg and 6 achieved CHR on Ropeg 50-400 mcg sc (mean 183.3±134.4) compared to Ropeg dose of CHR without DNMT3A (mean 203.2±131.8).We conclude that Ropeg improves expression of some HIF target genes, inflammatory genes, and prothrombotic genes (THBD and SELP) in neutrophils; also, HIF target genes and inflammatory gene expression in platelets compared to other PV & ET therapies. We also found that inflammation associated NFKB1 T haplotype is associated with decreased expression of inflammatory genes in neutrophils and that DNMT3A mutation does not preclude CHR by Ropeg therapy."

Clinical • Essential Thrombocythemia • Hematological Disorders • Inflammation • Myeloproliferative Neoplasm • Polycythemia Vera • Thrombocytosis • CXCL8 • DNMT3A • EDN1 • IL15 • IL1B • IL6 • LDHA • SELP • SERPINE1 • SLC2A1 • THBD

Interferon Synergizes with Inhibition of Pro-Apoptotic Proteins to Reduce Leukemia Burden in PDX Models of ML-DS (ASH 2024) - "Pegylated interferon alfa-2a (Pegasys, 24 μg/Kg, s.c.) dosing weekly for 6 weeks significantly prolonged survival of ML-DS PDX models in vivo...These data indicate that both Navitoclax and PRT1419 synergized with Pegasys to suppress leukemia burden in ML-DS PDX model. In summary, we showed that interferon signaling is suppressed in ML-DS blasts and interferon treatment reduced ML-DS cell viability in vitro and prolonged survival in vivo. Furthermore, interferon treatment in combination with Bcl-xL or MCL1 inhibition was superior in reducing leukemia burden compared to monotherapy."

Developmental Disorders • Genetic Disorders • Hematological Malignancies • Leukemia • Oncology • BCL2L1 • GATA1 • IFIH1 • PTPRC • STAG2 • STAT1

Real-World Experience of Ropeginterferon-Alfa Treatment of PV and ET - Two Centers Experience (ASH 2023) - "Prior to ropeginterferon-alfa, the participants were managed with therapeutic phlebotomies, or cytoreduced with either hydroxyurea, pegylated interferon-alpha 2a ( Pegasys), JAK2 inhibitors, or were newly diagnosed and previously untreated. Ropeginterferon-alfa is effective in PV and ET, however, the dose that achieves CHR is highly individualized, necessitating an incremental titration approach. The patients already in CHR from prior therapy needed relatively lower doses of ropeginterferon-alfa to maintain CHR. Clinical trials are ongoing with an alternate accelerated dosing scheme and results are awaited."

Clinical • Real-world • Real-world evidence • Cardiovascular • CNS Disorders • Depression • Dermatology • Essential Thrombocythemia • Fatigue • Genetic Disorders • Hematological Disorders • Mood Disorders • Myeloproliferative Neoplasm • Non-melanoma Skin Cancer • Oncology • Polycythemia Vera • Psychiatry • Skin Cancer • Squamous Cell Skin Cancer • Thrombocytosis • Thrombosis • CALR • DNMT3A • TET2

Ropeginterferon-alfa-2b (BESREMi) as a substitute for pegylated interferon-alfa-2a (Pegasys) in the management of mycosis fungoides and Sezary syndrome (EORTC-CLTG 2025) - No abstract available

Cutaneous T-cell Lymphoma • Mycosis Fungoides • Non-Hodgkin’s Lymphoma • Oncology • Sezary Syndrome

IB-001 IS A PARTIAL AGONIST OF THE TYPE I INTERFERON PATHWAY THAT EXHIBITS POTENT ANTI-HBV ACTIVITY WITH THE POTENTIAL FOR AN IMPROVED SAFETY PROFILE (AASLD 2025) - "Our data demonstrate that IB-001 confers potent antiviral activity against HBV and HDV in vitro and HBV in vivo with reduced inflammatory properties resulting in the potential for an improved tolerability and safety profile in the clinic."

Clinical • Hepatitis B • Hepatology • Infectious Disease • Inflammation • Respiratory Diseases • Respiratory Syncytial Virus Infections • IFNA1 • IFNAR1 • IFNAR2

PETALs: Nilotinib ± Peg-IFN for First Line Chronic Phase CML Patients (clinicaltrials.gov) - P3 | N=200 | Completed | Sponsor: Hospices Civils de Lyon | Unknown status ➔ Completed

Trial completion • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR

Peg-interferon for Inactive Chronic Hepatitis B Carriers (clinicaltrials.gov) - P2/3 | N=90 | Completed | Sponsor: Seng Gee Lim | Unknown status ➔ Completed

Trial completion • Hepatitis B • Infectious Disease • Inflammation

MHRA Approves pharmaand GmbH’s Pegasys (peginterferon alfa-2a) as a Treatment for Eligible Patients with the Myeloproliferative Neoplasms (MPNs) Blood Cancers Polycythemia Vera (PV) and Essential Thrombocythemia (ET) (pharma& Press Release) - "pharmaand GmbH (pharma&) announced today that the Medicines and Healthcare products Regulatory Agency (MHRA) has granted marketing authorization for Pegasys (peginterferon alfa-2a) as a monotherapy treatment for adults with polycythemia vera (PV) or essential thrombocythemia (ET)....The MHRA based its approval on a Phase 3 multicenter trial (MPD-RC 112, NCT01259856) and a Phase 2 multicenter trial (MPD-RC 111, NCT01259817) conducted by the Myeloproliferative Disorders Research Consortium (MPD-RC), both of which have been published in peer-reviewed journals in 2022 and 2019, respectively."

MHRA approval • Essential Thrombocythemia • Polycythemia Vera

DEEP MOLECULAR RESPONSES WITH LOW-FIXED DOSE OF ROPEGINTERFERON ALFA-2B IN A ROLLOVER COHORT OF THE LOW-PV TRIAL (EHA 2025) - "In this long-term follow-up of low-risk PV patients from the Low-PV trial, low-dose Ropeginterferon alfa-2b provided sustained hematologic control with no thrombotic events. Although the sample size was small, a significant proportion achieved deep molecular responses, comparable to dose-escalation strategies. These findings support the potential of tailored, lower-dose regimens to effectively suppress JAK2-mutant clones while optimizing efficacy, tolerability, and cost."

Acute Kidney Injury • Hematological Disorders • Infectious Disease • Polycythemia Vera • Renal Calculi • Renal Disease • Septic Shock • JAK2

pharma& Receives EMA approval for Pegasys manufacturing site variation (European Pharmaceutical Manufacturer) - "pharma& has announced that the European Medicines Agency (EMA) has granted a variation to the Marketing Authorisation for Pegasys (peginterferon alfa-2a), allowing Loba biotech, a wholly owned manufacturing subsidiary of pharma&, to be included as an approved site for the production of the active pharmaceutical ingredient (API), peginterferon alfa-2a...The approval enables pharma& to begin Pegasys product replenishment across Europe and bolsters enduring supply chain resilience. pharma& anticipates eligible European patients should start to experience improved Pegasys availability in the coming weeks."

Commercial • Essential Thrombocythemia • Hepatitis B • Hepatitis C • Polycythemia Vera

Targeted optimized interferon alpha demonstrates improved safety and efficacy in tumors with low PD-L1 expression (AACR 2025) - "REMD-456 was selected for its efficacy and safety profile in vitro and in vivo and manufacturability. It showed enhanced IFN activity only on PD-L1+ cells, resulting in an improved therapeutic window. In vivo, REMD-456 demonstrated superior anti-tumor efficacy in human tumor xenografts."

Clinical • IO biomarker • Oncology • IFNA1 • IFNAR1 • PD-L1

Safety, tolerability, pharmacokinetics, and pharmacodynamics of RO7565020, a novel monoclonal antibody that targets the hepatitis B surface antigen: results from a phase 1 single ascending dose study in healthy volunteers and participants with chronic hepatitis B (EASL 2025) - P1 | "Background and Aims: RO7565020 (RG6449) is a neutralizing human IgG1 monoclonal antibody (mAb) targeting the antigenic loop present in all forms of hepatitis B surface antigen (HBsAg). RO7565020 administered as a single dose was generally safe and well-tolerated. It demonstrated proof-of-mechanism with rapid reductions in serum HBsAg in participants with CHB who had baseline HBsAg ≤ 3000 IU/mL."

Clinical • P1 data • PK/PD data • Hepatitis B • Hepatitis C • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Inflammation

A Phase 1b/2a, Open-label,Randomized, Safety, Tolerability, Dose Finding, PK/PD, and Preliminary Efficacy Study of SC Hanferon™ in Combination With Ribavirin in Treatment-naïve Subjects With Genotype 1 Hepatitis C (clinicaltrials.gov) - P1/2 | N=30 | Completed | Sponsor: HanAll BioPharma Co., Ltd. | Phase classification: P1b/2a ➔ P1/2

Phase classification • Hepatitis C • Hepatology • Infectious Disease • Inflammation

SWITCH-1: Switching Regimen in Treating Cirrhotic HCV GT1b Subjects (clinicaltrials.gov) - P2 | N=138 | Completed | Sponsor: Humanity and Health Research Centre | Recruiting ➔ Completed | Trial completion date: Dec 2022 ➔ Oct 2024 | Trial primary completion date: Oct 2022 ➔ Oct 2024

Trial completion • Trial completion date • Trial primary completion date • Hepatitis C • Hepatology • Infectious Disease • Inflammation

HBsAg loss in Inactive Chronic Hepatitis B Carriers is Dependent on Level of qHBsAg and Interferon Response: A Randomised Control Trial (APASL 2025) - P2/3 | "HBsAg loss with PEG in inactive carriers leads to 16.7% HBsAg loss with low baseline qHBsAg and interferon responsiveness driving HBsAg loss but not HBV DNA. A novel neutrophil enriched pathway was found in responders based on transcriptome analysis Table and Figure:Figure 1. Figure 2."

Clinical • Fibrosis • Hepatitis B • Hepatitis C • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Inflammation • MMP8

Clinical aspects of Hepatitis Delta - a retrospective analysis of patients' data from 2004 to 2024 (APASL 2025) - "Dual HBV/HDV infection is one of the most rapidly progressive causes of advanced liver disease that can end up with dangerous complications such as cirrhosis and HCC. The prevalence of HDV infection is 13,4 % in HBsAg-positive individuals. The results of our study suggest that co-infection with hepatitis B and D viruses could represent an important cause of liver disease in certain populations."

Retrospective data • Fibrosis • Hepatitis B • Hepatocellular Cancer • Hepatology • Infectious Disease • Inflammation • Liver Cirrhosis • Oncology • Solid Tumor

MORPHEUS BC: A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Participants With Breast Cancer (clinicaltrials.gov) - P1/2 | N=510 | Recruiting | Sponsor: Hoffmann-La Roche | Trial primary completion date: Apr 2026 ➔ Nov 2027

Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER

MORPHEUS BC: A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Participants With Breast Cancer (clinicaltrials.gov) - P1/2 | N=316 | Recruiting | Sponsor: Hoffmann-La Roche | N=510 ➔ 316

Enrollment change • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER

PharmaEssentia Highlights Availability of BESREMi (ropeginterferon alfa-2b-njft) for Patients Affected by Pegasys (peginterferon alfa-2a) Drug Shortage (Businesswire) - "PharmaEssentia USA Corporation...today announced that the latest National Comprehensive Cancer Network (NCCN) Guidelines (Version 1.2025, January 21, 2025) now highlight the substitution of ropeginterferon alfa-2b-njft (BESREMi) for treating polycythemia vera (PV) in the event that peginterferon alfa-2a (Pegasys) is unavailable....The updated NCCN Guidelines come at a crucial time, as an ongoing Pegasys shortage poses challenges in treatment continuity."

NCCN guideline • Polycythemia Vera

NCCN has published updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) and the NCCN Imaging Appropriate Use Criteria (NCCN Imaging AUC) for Systemic Mastocytosis, Version 1.2025. (NCCN)

NCCN guideline • Aggressive Systemic Mastocytosis

A Study to Evaluate the Safety, Tolerability, Drug Levels, Food, Formulation, and pH Effects on Relative Absorption of BMS-986465 and Its Active Derivative BMS-986464 in Healthy Participants (clinicaltrials.gov) - P1 | N=267 | Terminated | Sponsor: Bristol-Myers Squibb | N=132 ➔ 267 | Trial completion date: Mar 2025 ➔ Oct 2024 | Active, not recruiting ➔ Terminated | Trial primary completion date: Mar 2025 ➔ Oct 2024; Business objectives have changed

Enrollment change • Trial completion date • Trial primary completion date • Trial termination