A Phase 3 clinical trial is underway to assess the long-term safety and efficacy of Ropeginterferon alfa-2b (P1101) compared to anagrelide (ANA) as a second-line treatment for patients with high-risk essential thrombocythemia (ET) who have shown intolerance or resistance to hydroxyurea (HU). The open-label, multicenter, randomized, active-controlled study, known as SURPASS-ET, aims to evaluate the efficacy, safety, and tolerability of P1101 over 12 months of treatment, including a 28-day screening and follow-up period, for a total trial duration of 14 months.
Study Design and Patient Population
The trial involves 58 sites worldwide and has randomized 101 patients to date (45 men and 56 women). The mean age at recruitment was 58.9 years, with a median age of 62 years (range 21 to 80 years). Participants are patients diagnosed with high-risk ET, defined as either being older than 60 years and JAK2V617F-positive at screening or having a history of thrombosis or hemorrhage, according to WHO 2016 criteria. All patients had documented resistance or intolerance to HU and were interferon-naive. Key exclusion criteria included pregnant females, autoimmune disease, and a history or presence of clinically significant depression.
Treatment Regimen
P1101 is administered subcutaneously every two weeks, starting with a dose of 250 mcg (Week 0), escalating to 350 mcg (Week 2), and reaching a target 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.
Primary Outcome
The primary endpoint of the study is durable modified European LeukemiaNet (ELN) composite response at 9 and 12 months from the start of dosing. This composite endpoint assesses the overall treatment response based on hematological and clinical parameters.
Current Treatment Landscape and Unmet Needs
Low-dose aspirin with hydroxyurea (HU) is the current first-line therapy for high-risk ET. However, a significant number of patients develop intolerance or resistance to HU, necessitating second-line treatment options. Anagrelide and peginterferon alfa-2a are currently used as second-line options. This trial seeks to provide evidence comparing P1101 with anagrelide, the only approved treatment option in this setting, addressing a critical unmet need for effective and well-tolerated therapies.
Interim Findings and Monitoring
Seventy-nine subjects had a TSS <20. The study is overseen by a Data and Safety Monitoring Board (DSMB), which has not identified any need to intervene, indicating the trial is proceeding as planned. The results of this study are expected to provide valuable insights into the management of high-risk ET patients who have failed first-line therapy.
