Ropeginterferon alfa-2b demonstrated superior efficacy and safety compared with anagrelide as second-line therapy for patients with essential thrombocythemia (ET) who were intolerant or resistant to hydroxyurea, according to data from the phase III SURPASS-ET trial presented at the European Hematology Association (EHA) 2025 Congress.
At 12 months, 42.9% of patients treated with ropeginterferon alfa-2b achieved the primary endpoint—a sustained response per Modified European LeukemiaNet (ELN) criteria—compared with 6.0% in the anagrelide group (P = .0001). The drug also demonstrated superior control in platelet and white blood cell counts, improvements in spleen size, symptom reduction, and significantly fewer thrombotic events (1.1% vs 8.8%) versus anagrelide.
"These compelling results support ropeginterferon as a promising new therapeutic option with disease-modifying potential in ET," said lead study author Harinder Gill, MD, PDipID, MBBS, Clinical Associate Professor in the Department of Medicine at the School of Clinical Medicine, University of Hong Kong.
Addressing Unmet Medical Need
Essential thrombocythemia is a chronic myeloproliferative neoplasm characterized by excessive platelet production, which increases the risk of thrombohemorrhagic events and potential progression to myelofibrosis or acute leukemia. Current first-line treatments primarily involve hydroxyurea and anagrelide; however, no new therapies have been approved in the United States for the condition since anagrelide in 1997.
Ropeginterferon alfa-2b, approved globally for polycythemia vera, offers cytoreductive and disease-modifying potential, warranting investigation in ET. The SURPASS-ET trial randomly assigned 174 participants across 59 sites globally, comparing ropeginterferon alfa-2b (n = 91) with anagrelide (n = 83). Eligible patients had high-risk ET, prior intolerance or resistance to hydroxyurea, and were interferon-naive or anti–ropeginterferon alfa-2b antibody–negative.
Significant Molecular and Clinical Responses
Ropeginterferon alfa-2b dosing began at 250 μg initially, escalating to a maintenance dose of 500 μg biweekly. The trial met its primary endpoint, with patients achieving significantly higher modified ELN response rates at 9 and 12 months with ropeginterferon alfa-2b compared with anagrelide. The drug demonstrated superior individual responses in platelet and white blood cell control, symptom improvement, and reduction in splenomegaly, alongside the absence of thrombotic complications.
Notably, ropeginterferon alfa-2b demonstrated substantial molecular responses, a critical secondary endpoint. Partial molecular responses were observed in 27.8% of patients, with complete molecular responses in 2.8%. Significant reductions in JAK2 V617F variant allele frequency and CALR mutations were recorded, with no molecular responses observed in the anagrelide group. Two patients with CALR mutations achieved complete molecular responses.
Superior Safety Profile
Ropeginterferon alfa-2b was associated with significant symptom reduction, with higher proportions of patients achieving more than 25% and 50% improvement compared with anagrelide. The drug also substantially lowered thromboembolic and cardiovascular event rates (1.1%) versus anagrelide (10%).
Regarding safety, fewer severe (grade ≥ 3) treatment-emergent adverse events occurred with ropeginterferon (23%) compared with anagrelide (34%). Treatment discontinuations from adverse events were also markedly lower with ropeginterferon (5.5%) versus anagrelide (20%). The most common adverse event in the ropeginterferon arm was transaminitis, which was predominantly mild, whereas anagrelide was frequently associated with palpitations and headaches.
Importantly, ropeginterferon alfa-2b treatment resulted in no cases of disease progression to myelofibrosis or acute leukemia, conditions observed in 3.6% of patients receiving anagrelide.
"Further investigation is warranted to expand on the efficacy and safety findings of ropeginterferon in patients with high-risk ET," Dr. Gill concluded.
