Ropeginterferon alfa-2b (P1101) is under investigation as a potential second-line treatment for patients with high-risk Essential Thrombocythemia (ET) who have developed resistance or intolerance to hydroxyurea (HU). The Phase 3 SURPASS-ET trial is comparing P1101 to anagrelide (ANA), currently the only approved treatment option for this patient population. The study aims to assess the long-term safety and efficacy of P1101 over a 12-month treatment period.
The open-label, multicenter, randomized, active-controlled study involves 136 patients across 61 international sites. Participants include those diagnosed with high-risk ET according to WHO 2016 criteria, defined as either being >60 years and JAK2V617F-positive or having a history of thrombosis or hemorrhage. All patients had documented HU resistance or intolerance and were interferon-naïve. Key exclusion criteria included pregnant females, autoimmune disease, and a history of clinically significant depression.
Study Design and Treatment
P1101 is administered subcutaneously every two weeks, starting at 250 mcg (Week 0), escalating to 350 mcg (Week 2), and targeting an optimal dose of 500 mcg (Week 4) for the remainder of the treatment period. ANA is dosed according to local country label. All subjects receive low-dose aspirin unless contraindicated.
The primary endpoint of the SURPASS-ET trial is the durable modified European LeukemiaNet (ELN) composite response at 9 and 12 months from the start of dosing. This composite endpoint assesses hematological response and disease progression. Secondary endpoints include safety, tolerability, and other measures of disease control.
Current Treatment Landscape and Unmet Needs
Low-dose aspirin with hydroxyurea is often the preferred first-line therapy for high-risk ET. However, a significant proportion of patients develop intolerance or resistance to HU, necessitating alternative treatment options. While anagrelide and peginterferon alfa-2a are used, there remains a need for more effective and well-tolerated therapies. The SURPASS-ET trial seeks to address this unmet need by providing evidence for P1101 as a second-line treatment.
Interim Results and Ongoing Monitoring
To date, 136 patients have been randomized (64 men and 72 women) with a mean age of 58.5 years. The study is overseen by an independent Data and Safety Monitoring Board (DSMB), and no need for intervention has been identified. The results of the SURPASS-ET trial are expected to provide valuable insights into the potential of P1101 as a second-line treatment option for high-risk ET patients who are resistant or intolerant to hydroxyurea.
