Besremi (ropeginterferon alfa-2b-njft) / PharmaEssentia, AOP Orphan Pharma, Pint Pharma - LARVOL DELTA

Clinical features and outcomes of myeloproliferative neoplasm patients with MPL mutations and concurrent JAK2/calr mutations (ASH 2025) - "ET treatments included hydroxyurea and off-label Ropeginterferon alfa-2b. Among those with MF, 7 patients received ruxolitinib, 2 required anemia-related therapies, including darbepoetin alfa and Luspatercept...However, further work is required to investigate this hypothesis. Limited follow-up and the predominance of White populations in our cohort underscore the need for studies involving larger and more diverse populations with extended longitudinal data to better understand the prognostic significance and therapeutic implications of the co-mutations."

Clinical • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Myelofibrosis • Myeloproliferative Neoplasm • Thrombocytosis • ASXL1 • CALR • JAK2 • NOTCH1 • SF3B1 • SH2B3 • SRSF2 • TET2

Long term outcomes of ET and PV patients after clinical trial treatment with interferon alfa (ASH 2025) - "Hydroxyurea (HU) is the most frequently utilized first-line cytoreductive agent, however pegylated interferon alpha-2a (PEG) and the more recently approved, ropeginterferon alfa-2b (ropeg-IFN), have demonstrated a potential to induce molecular responses and improve event free survival (EFS) (Gisslinger Leukemia 2023). This analysis also demonstrated high rates of PEG-related toxicities, although definitive causality was often difficult to determine. Additional clinical and molecular data will be available at the time of the meeting."

Clinical • Bone Marrow Transplantation • Chronic Eosinophilic Leukemia • CNS Disorders • Depression • Endocrine Disorders • Essential Thrombocythemia • Hematological Malignancies • Hepatology • Immunology • Infectious Disease • Leukemia • Liver Failure • Mood Disorders • Myelofibrosis • Myeloproliferative Neoplasm • Polycythemia Vera • Septic Shock • Thrombocytosis • Thrombosis • CALR • JAK2

Interferon therapy achieves potent reduction in JAK2 allele burden in patients with myeloproliferative neoplasms: A real-world analysis (ASH 2025) - " This single center, retrospective study evaluated consecutive pts treated with pegylated interferon alfa-2a (peg-IFN) or ropeginterferon alfa-2b (ropeg), regardless of line of therapy...Prior therapy included hydroxyurea, anagrelide, and ruxolitinib in 36 (43.9%), 2 (2.4%), and 8 (9.8%) pts, respectively; 44 had not received prior cytoreductive therapy... This real-world analysis demonstrates the feasibility and efficacy of IFN therapy in clinical practice. Most pts achieved sustained CHR with low treatment discontinuation rate; thrombotic and disease progression events were rare. Importantly, we demonstrate the substantial impact of IFN on reducing JAK2 allele burden."

Clinical • Real-world • Real-world evidence • Acute Myelogenous Leukemia • Essential Thrombocythemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelofibrosis • Myeloproliferative Neoplasm • Polycythemia Vera • Thrombocytosis • Thrombosis • JAK2 • NPM1

Real-world hematologic response and treatment patterns among patients with polycythemia vera (PV) treated with ropeginterferon alfa-2b (ropeg) (ASH 2025) - "While cytoreductive therapy, particularly hydroxyurea (HU), has been a mainstay treatment, ropeg has emerged as a promising new treatment approach based on recent trial results, subsequent FDA approval, and inclusion as a NCCN Guideline preferred treatment...Among 2L+ patients, prior therapies included HU (71%), ruxolitinib (25%), peginterferon alfa-2a (6%), and interferon alfa-2b (1%)...These findings support the effectiveness of ropeg in community practice populations and provide benchmarks for future studies. Further research, including abstraction of unstructured data, is warranted to explore more details on dosing, duration of therapy, adverse effects, driver mutations, allele burden declines, and long-term outcomes."

Clinical • Real-world • Real-world evidence • Chronic Eosinophilic Leukemia • Hematological Disorders • Myeloproliferative Neoplasm • Polycythemia Vera

Retrospective real-world analysis of ropeginterferon ALFA-2B use in patients with polycythemia vera and essential thrombocythemia: Practice patterns, tolerance, and outcomes (ASH 2025) - "Forty-two percent (n=36/85) received concurrent hydroxyurea (median overlap 11 weeks; range 1–97 weeks) when starting ropeg. The most common starting dose of ropeg was 100 mcg every 2 weeks (73%, n=62; range 50–300 mcg q2 weeks). We present the latest real-world data on ropeginterferon use confirming its efficacy in achieving CHR and reducing JAK2 allele burden. At 6 months 44% had achieved a CHR. Seventy percent of patients experienced a decline in JAK2 VAF."

Real-world • Real-world evidence • Retrospective data • CNS Disorders • Depression • Dermatology • Essential Thrombocythemia • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Mental Retardation • Mood Disorders • Myelofibrosis • Myeloproliferative Neoplasm • Polycythemia Vera • Pruritus • Thrombocytosis • JAK2

Changes in neutrophil-to-lymphocyte ratio (NLR) in patients with polycythemia vera treated with ruxolitinib reflect changes of JAK2 variant allele frequency (VAF) (ASH 2025) - "Forty pts with PV who received ruxo, 10 mg BID for a median of 8.7y (4.7-9.8) as second linetherapy because of intolerance (44.2%) or resistance (55.8%) to hydroxyurea, were included. Findings are reminiscent of observations in PV pts treated with ropeg-interferon inthe LOW-PV and PROU-PV/CONTINUATION-PV study (Barbui T, EHA 2024). These findings deserveconfirmation in other cohorts of ruxo-treated PV pts."

Clinical • Polycythemia Vera • Thrombosis • JAK2

Clinical significance of earlier CHR achievement and long-term CHR maintenance in polycythemia vera patients treated with ropeginterferon alfa-2b (ASH 2025) - "This study demonstrates that a rapid dose-escalation strategy of ropeginterferon alfa-2bachieved high rates of both CHR and MR with durable maintenance in patients with PV who requiredcytoreductive therapy. Notably, earlier achievement of CHR was significantly associated with sustainedlong-term CHR maintenance, highlighting the importance of prompt therapeutic response from theperspective of the timely treatment optimization. These results underscore the need for treatmentstrategies that prioritize earlier CHR achievement to ensure durable long-term remission."

Clinical • Myeloproliferative Neoplasm • Polycythemia Vera

Ropeginterferon alfa-2b in 248 patients with polycythemia vera: Results from the italian cohort of a prospective, non-interventional, post-authorization study (ROPEG-PV) (ASH 2025) - P | "In Italy, use isrestricted to patients intolerant to hydroxyurea (HU), women of childbearing who intend to becomepregnant, and individuals with a history of skin cancer...Prior treatments included HU (82%), PHL (71%), and ruxolitinib(18%)... Among 248 patients with JAK2 V617F or exon 12-mutation (VAF 38% to 59%), 238 started thetreatment; 10 of them are in screening. Median follow-up was 12 months.A. Patient Characteristics:(i) HU-intolerant patients (N=152)Mostly male (66%), median age 60, 20% had splenomegaly."

Clinical • CNS Disorders • Endocrine Disorders • Genetic Disorders • Infectious Disease • Macular Degeneration • Myelofibrosis • Non-melanoma Skin Cancer • Obstetrics • Polycythemia Vera • Renal Disease • Retinal Disorders • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Thrombosis • JAK2

Ruxolitinib and interferon alfa induce superior rates of complete peripheral blood count remission compared to anagrelide in hydroxyurea-exposed essential thrombocythemia (ASH 2025) - "Introduction: Essential thrombocythemia is a myeloproliferative neoplasm characterized by elevatedplatelets and a predilection for thrombotic events. Here, we present the largest known comparison of cytoreductive agents in HU-exposedET patients revealing that though ANA is a commonly prescribed 2nd-line cytoreductive agent, ANA mayinduce inferior rates of CPBCR at 1 year of therapy compared to either RUX or IFN. Furthermore, wereveal that IFN, which includes both PEG and ROPEG, may have superior CPBCR rates compared to RUXwhen matched for age, sex, race, and baseline blood counts. Analyses regarding rates of thrombosis andtransformation to myelofibrosis are ongoing and will be presented at the conference."

Clinical • Essential Thrombocythemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelofibrosis • Thrombocytosis • Thrombosis

Rapid JAK2 V617F decline predicts response durability: Kinetics of JAK2 V617F in ropeginterferon alfa-2b treated polycythemia vera (ASH 2025) - "This study provides new information on JAK2 kinetics during ropeginterferon alfa-2btreatment with rapid dose escalation. JAK2 declines a mono-exponentially in many patients onropeginterferon alfa-2b, with population-level reduction below 10% requiring approximately 486.1 days.These results suggest maintaining ropeginterferon alfa-2b treatment for at least 1.3 years to monitor thedecline in JAK2. In addition, rapid JAK2 reduction may have a lower tendency for CHR loss and MR loss,suggesting that a treatment strategy that induces a rapid decrease in JAK2 may be important for long-term remission."

Cardiovascular • Coronary Artery Disease • Hematological Disorders • Myelofibrosis • Polycythemia Vera • Thrombosis • JAK2 • KIT

A randomized study of ropeginterferon in combination with bosutinib in newly diagnosed chronic myeloid leukemia (CML) patients in chronic Phase. the bosupeg trial from the Nordic CML study group (ASH 2025) - "Introduction: Prior studies combining pegylated interferon-α to Imatinib and Nilotinib in newly diagnosedCML patients have indicated an additive effect with faster and deeper molecular responses (SPIRIT,TIGER, NordCML002, NiloPEG). In this trial we used a bosutinib (BOS) backbone combined with low-doseropeginterferon alfa-2b (BESREMi, AOP Health), which in contrast to previously tested interferons has alonger half-life and a more favorable tolerability profile...Most switched patients received 1st and 2nd generation TKIs, butsome were transplanted or received ponatinib... The step-up dosing strategy for BOS reduced GI toxicity, but not transaminitis. Efficacy wasexcellent in comparison with the registration study (BFORE). The combination of ropeginterferon andBOS was safe and efficacious."

Clinical • Combination therapy • Chronic Myeloid Leukemia • CNS Disorders • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Mental Retardation

Fedora preliminary analysis of a Phase II study evaluating the tolerability, safety and activity of fedratinib combined with ropeginterferon alfa-2b in patients with myelofibrosis. (ASH 2025) - "The combination of the JAK2 inhibitor fedratinib and ropeg interferon alfa-2b appearstolerable and safe. Symptom score responses and spleen reductions were observed and encouragingreductions in JAK2 allele burden seen in a proportion."

Clinical • P2 data • Myelofibrosis • Myeloproliferative Neoplasm • Ocular Inflammation • Ophthalmology • Uveitis

Ropeginterferon alfa-2b in essential thrombocythemia of all risk levels ineligible for standard cytoreduction: 12-month primary endpoint analysis from the ROP-ET phase 3 study (ASH 2025) - P3 | "Moreover, these treatments are often limited by intolerance, resistance orcontraindications, leaving a substantial proportion of patients without satisfactory therapeutic options.Ropeginterferon alfa-2b (BESREMi®), a mono-pegylated, next-generation interferon alfa, approvedglobally for polycythemia vera with the potential to modify disease course, is being studied to addressthis unmet need.MethodsThis fully recruited, ongoing, phase 3, prospective, multicenter, single-arm study (ROP-ET; NCT06514807)enrolled adults with ET according to WHO 2016 criteria requiring cytoreduction, who were intolerant orresistant and/or ineligible for all locally approved cytoreductive therapies including hydroxyurea (HU),anagrelide (ANA), busulfan (BUS) and pipobroman (PB). In this last-linepopulation, treatment with ropeginterferon alfa-2b was well tolerated, with few discontinuations due toadverse events. The planned primary endpoint analysis will provide data on the efficacy..."

P3 data • Essential Thrombocythemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelofibrosis • Myeloproliferative Neoplasm • Polycythemia Vera • Thrombocytosis • Thrombosis • CALR • JAK2

634. Myeloproliferative Syndromes: Clinical and Epidemiological: Between a Rock and a Ropeg - Innovative Therapies for MPNs (ASH 2025) - No abstract available

Clinical • Myelodysplastic Syndrome

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

Impact of early dose escalation and treatment duration on hematologic response in ropeginterferon alfa-2b treatment for polycythemia vera (ASH 2025) - "The analysis was conducted on a longitudinal dataset, including repeated observationsfor each patient.ResultsAmong the 133 patients analyzed (median age 53.4 years, range 19-85; 69.9% male), most (78.2%, n=104)had previously been treated with hydroxyurea; of these, two had also received ruxolitinib. Additionally, recent evidence suggests thatstarting with a higher dose and implementing a more rapid titration schedule (e.g., 250-350-500 mcg)may result in faster hematologic remission, with CHR rates at six months comparable to those typicallyseen at twelve months using conventional low-dose, slow-escalation regimens. Though directcomparisons are lacking, these data point to the potential value of more proactive, individualized doseadjustments."

Hematological Disorders • Polycythemia Vera • Pruritus

Interferon alfa treatment of early primary myelofibrosis is associated with improved overall survival (ASH 2025) - "In the NoIFN group, 17(37%) were on observation only, and others received one or more cytoreductive therapy includingruxolitinib (26%), hydroxyurea (28%), or other (30%). In our retrospective analysis of 92 pts with early PMF, treatment with IFN yielded superior OS.MVA confirmed that this survival benefit was independent of age and DIPSS+ lab parameters, supportingthe use of IFN for early PMF. Randomized controlled trials are needed to validate and further assess theadvantages of IFN on both short and long-term outcomes. The upcoming HOPE-PMF phase 3 trialevaluating ropeginterferon alfa-2b vs observation in early PMF pts (Abu-Zeinah et al."

Clinical • Bone Marrow Transplantation • Hematological Disorders • Myelofibrosis • CALR • JAK2

Transcriptomic signatures associated with deep molecular response to ropeginterferon alfa-2b in polycythemia vera (ASH 2025) - "DMR, defined by an absoluteJAK2 V617F allele burden <2%, may serve as a more robust surrogate marker. Transcriptomic profilingsupports DMR as a biologically distinct state, highlighting the potential role of immune-related molecularsignatures in future response assessments."

Hematological Malignancies • Leukemia • Polycythemia Vera • JAK2

Long-term efficacy and safety of ropeginterferon alfa-2b under its hidat regimen for the treatment of polycythemia vera (ASH 2025) - "Nopatients developed disease progression to secondary myelofibrosis or acute myeloid leukemia on thestudy, and only one major thrombosis and two bleeding events occurred.In conclusion, long-term ropeg administration under an optimized HIDAT regimen effectively sustainsCHRs, induces profound molecular responses, and exhibits favorable safety in hydroxyurea-intolerant PVpatients. Achieving CMR correlated with improved EFS, highlighting its prognostic significance."

Clinical • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelofibrosis • Myeloproliferative Neoplasm • Polycythemia Vera • Thrombosis • ABL1

Final results from a prospective, multicenter, non-interventional study (BESREMi-PASS) on the safety of ropeginterferon alfa-2b in 229 patients with polycythemia vera (ASH 2025) - "Despite pre-existing liver disease in 17% of patients, hepatoxicity on ropeg occurred at a low overall rate, consistentwith registration trials and prescribing information. In contrast to trial populations, substantial co-morbidity was observed, with more cardiovascular events in patients with history of cardiovascular risk.Our prospective investigation of a large PV cohort confirms the safety of ropeginterferon alfa-2b in a real-world setting."

Clinical • Observational data • Cardiovascular • CNS Disorders • Depression • Dermatology • Endocrine Disorders • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Myocardial Infarction • Polycythemia Vera • Pruritus • Psychiatry

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

Towards New Therapy Endpoints in Polycythemia Vera: Targeting Clonal and Inflammatory Pathways. (PubMed, Blood Adv) - "Although phlebotomy and hydroxyurea (HU) are standard first-line therapies for polycythaemia vera (PV), they do not adequately address clonal expansion and chronic inflammation - key drivers of thrombosis, myelofibrosis and mortality...Ropeginterferon alfa-2b has been shown to reduce both JAK2 VAF and NLR, improving event-free survival as demonstrated in the Low-PV and PROUD-PV/CONTINUATION-PV trials...Although no data on NLR dynamics with ruxolitinib have been published, the anti-inflammatory effects of ruxolitinib and its suppression of JAK2 VAF suggest it may exert similar biological activity. These findings support a shift towards biology-guided treatment in PV, recognising that inflammation and JAK2 VAF could serve as surrogate endpoints in future clinical trials."

Journal • Cardiovascular • Hematological Disorders • Inflammation • Myelofibrosis • Polycythemia Vera • Thrombosis

Phase II Study Assessing the Safety and Efficacy of Dasatinib in Combination With Ropeginterferon in Patients With Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (clinicaltrials.gov) - P2 | N=40 | Not yet recruiting | Sponsor: M.D. Anderson Cancer Center

New P2 trial • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Hemato-Oncology Trials: AOP Health Presents New Results at Top Congress ASH (Businesswire) - "The company, specialized in rare diseases, presented the results of two scientific investigations....One of the clinical studies, ROP-ET, examined the use of ropeginterferon alfa-2b in people with essential thrombocythemia (ET)....The trial, a prospective, multicenter, single-arm phase III study, investigated the safety and efficacy of ropeginterferon alfa-2b in ET patients unable to receive available cytoreductive therapies. The other investigation, the BESREMi-PASS study, looked at how the medicine performs in everyday clinical practice among people with polycythemia vera (PV)."

Clinical data • Essential Thrombocythemia • Polycythemia Vera

Evaluating the feasibility of a network meta-analysis comparing treatment options in polycythemia vera. (PubMed, J Comp Eff Res) - "A targeted literature review and feasibility assessment for an indirect comparison of ropeginterferon alfa-2b-njft versus peginterferon alfa-2a or ruxolitinib, using standard of care comprising hydroxyurea (HU) as a common comparator was conducted. An NMA for PV treatments was not feasible due to significant clinical and methodological heterogeneity across studies, including differences in patient characteristics, treatments, outcome definitions and follow-up times. These findings highlight the importance of standardized clinical trial designs and outcome definitions to enable robust comparative evidence generation for rare conditions like PV."

Journal • Retrospective data • Chronic Eosinophilic Leukemia • Hematological Disorders • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera