Myelofibrosis is a rare type of myeloproliferative neoplasm characterized by bone marrow fibrosis and disrupted blood cell production, affecting approximately 19,492 cases in the US. Currently, there is no established standard of care for managing primary myelofibrosis (PMF) in its pre- or early fibrotic stages, or for patients with low to intermediate-1 risk according to DIPSS. 

At the EHA 2025 Congress, findings from the Phase II trial of ropeginterferon alfa-2b in myelofibrosis patients were presented. It demonstrated good tolerability and showed clinical, hematologic, and molecular efficacy in patients with pre-fibrotic and low to intermediate-1 risk myelofibrosis. 

As of the data cut-off on June 30, 2024, a total of 71 patients with a median age of 60 years were enrolled. At a median follow-up of 119 weeks, clinical response rates for hemoglobin, white blood cells, and platelets at Week 24 were 73.9%, 82.6%, and 100%, respectively, and remained consistent at Week 52 (76.2%, 79.4%, and 100%). A reduction in JAK2V617F variant allele frequency (VAF) was observed in 34% of evaluable patients (16/47) at Week 24 and 44% (20/41) at Week 52. For patients with CALR mutations, VAF reductions were noted in 53% (10/19) at Week 24 and 43% (6/14) at Week 52. Spleen size reduction was seen in 47% (9/19) at Week 24 and 53% (9/17) at Week 52. Additionally, a ≥50% reduction in symptom burden (MPNSAF-TSS) was achieved in 42.9% (27/63) of patients at Week 24 and 42.1% (23/57) at Week 52.

The most common non-hematologic AEs included transaminitis (Grade 1–2, 49.2%); malaise (Grade 1–2: 40.8%; Grade 3–4: 1.4%), and hair loss (Grade 1–2: 33.8%). The most common hematologic AEs were anemia (Grade 1–4: 21.1%; Grade 3-4: 8.5%), neutropenia (Grade 1–2: 21.1%; Grade 3–4: 5.6%) and thrombocytopenia (Grade 1–2: 11.2%; Grade 3–4: 4.2%). Thrombohemorrhagic events or progression to blast-phase myelofibrosis were not observed during the study.

KOL insights

“There is currently no approved therapy for patients with prefibrotic or low/intermediate-1 risk myelofibrosis per DIPSS; most are observed or receive cytoreductive oral chemotherapy, with limited benefit from JAK inhibitors unless symptomatic splenomegaly is present. These patients, especially younger ones, are still at risk for vascular events and disease progression, highlighting the urgent need for treatments that not only manage blood counts but also offer true disease modification.” – Expert Opinion

Conclusion

The myelofibrosis treatment landscape is rapidly advancing, with four key JAK inhibitors—JAKAFI (ruxolitinib), OJJAARA (momelotinib), VONJO (pacritinib), and INREBIC (fedratinib)—currently approved. While JAKAFI has long dominated the market, its position may be increasingly challenged by BESREMi, which offers a novel, disease-modifying approach. Unlike traditional JAK inhibitors, BESREMi exerts its effects indirectly via IFNAR-mediated activation of the JAK/STAT pathway, contributing to reduced mutation burden and sustained hematologic control. Its long-acting profile and potential for early intervention make it particularly well-suited for patients with early-stage or lower-risk myeloproliferative neoplasms, positioning it as a differentiated and competitive alternative in an evolving therapeutic landscape. 

Ropeginterferon alfa-2b, a next-generation mono-pegylated interferon specifically developed for myeloproliferative neoplasms (MPNs), is being explored as a potential treatment option in these settings. It is a long-acting mono-pegylated interferon designed for extended activity and flexible dosing—administered biweekly or monthly in stable cases. Already approved for polycythemia vera, it is currently being evaluated in clinical trials for additional indications, including essential thrombocythemia, early-stage myelofibrosis, adult T-cell leukemia, and CML. Its potential to modify the course of disease—along with a well-tolerated safety profile—reinforces its value as a therapeutic option. These advantages, combined with its differentiated approach, suggest that ropeginterferon alfa-2b could meaningfully compete with established JAK inhibitors, particularly in early-stage or lower-risk patients seeking long-term disease control.

Increasing competition in the myelofibrosis market, ropeginterferon alfa-2b is emerging as a strong alternative to JAK inhibitors, particularly JAKAFI, which has long dominated the space. Its prior approval in polycythemia vera, along with encouraging real-world evidence and a positive Phase III readout in essential thrombocythemia, strengthens its regulatory prospects in myelofibrosis. Combined with growing physician confidence in its safety, efficacy, and long-acting profile, ropeginterferon alfa-2b is well-positioned to shift treatment paradigms and capture meaningful market share.