Ropeginterferon Alfa-2b (P1101) vs. Anagrelide in Essential Thrombocythemia Patients With Hydroxyurea Resistance or Intolerance

Inclusion Criteria: 1. Male or female subjects ≥18 years old 2. Subjects diagnosed with high-risk ET (either older than 60 years and JAK2V617-positive at screening, or having disease-related thrombosis or hemorrhage in the past), diagnosed according to the World Health Organization (WHO) 2016 criteria 3. Subjects have received prior HU for ET, while the washout between the last dose of HU and randomization should not be shorter than 7 days 4. Interferon treatment-naïve, or anti-P1101 binding antibody negative at screening and the washout between last dose of interferon and randomization should not be shorter than 14 days. 5. Documented resistance/intolerance to prior HU for ET, referencing modified ELN criteria (Barosi, et al, 2007), whereby at least one of the following criteria is met: Platelet count \>600 x 10\^9/L at ≥2 g/day (or ≥2.5 g/day if subject body weight \>80 kg) or maximally tolerated dose if \<2 g/day after at least 3 months of HU, or Platelet count \>400 x 10\^9/L and WBC count \<2.5 x 10\^9/L at any dose and any duration of HU, or Platelet count \>400 x 10\^9/L and hemoglobin (HGB) \<10 g/dL at any dose and any duration of HU, or Presence of HU-related toxicities at any dose and any duration of therapy (e.g., leg ulcers, mucocutaneous manifestations, pneumonitis, or HU-related fever), or Platelet count \>450 x 10\^9/L at any dose and any duration of HU. The actual dose and duration of HU must be recorded on the eCRF. Moreover, if patient received one dose of HU, the reason why subject was judged to be HU resistance/intolerance must be recorded on the eCRF. 6. Platelets \>450 x 10\^9/L at screening 7. WBC \>10 x 10\^9/L at screening 8. HGB ≥11 g/dL at screening for males and 10 g/dL at screening for females 9. Neutrophil count ≥1.0 x 10\^9/L at screening 10. Adequate hepatic function defined as bilirubin ≤1.5 x upper limit normal (ULN), prothrombin time (PT) (international normalized ratio, INR) ≤1.5 x ULN, albumin \>3.5 g/dL, alanine aminotransferase ≤2.0 x ULN, aspartate aminotransferase ≤2.0 x ULN at screening 11. Creatinine clearance ≥40 mL/min (by Cockcroft-Gault equation) 12. Males and females of childbearing potential, as well as all women \<2 years after the onset of menopause, must agree to use an acceptable form of birth control until 28 days following the last dose of the study drug, and females must agree to not breastfeed during the study 13. Written informed consent obtained from the subject and ability for the subject to comply with the requirements of the study Exclusion Criteria: 1. Any subject requiring a legally authorized representative 2. Any contraindications or hypersensitivity to IFN-α or ANA and their excipients 3. Known risk factors for QT-prolongation (e.g., congenital long QT, known history of acquired QT-prolongations). Medications that can prolong QTc and induce hypokalemia will not be allowed in the study. 4. Co-morbidity with severe or serious condition that, in the Investigator's opinion, would jeopardize the safety of the subject or their compliance with the protocol, including significant cardiac disease (including New York Heart Association Class III-IV congestive heart failure and clinically significant arrhythmias) and pulmonary hypertension 5. History of major organ transplantation 6. Pregnant or lactating females 7. Subjects with any other significant medical conditions that, in the opinion of the Investigator, would compromise the results of the study or may impair compliance with the requirements of the protocol, including but not limited to: 1. Documented autoimmune disease at screening or in the history (e.g., thyroid dysfunction, hepatitis, idiopathic thrombocytopenic purpura, scleroderma, psoriasis, or any arthritis of autoimmune origin) 2. Clinically relevant pulmonary infiltrates, pneumonia, and pneumonitis at screening that, in the Investigator's opinion, would jeopardize the safety of the subject or their compliance with the protocol 3. Infections with systemic manifestations (e.g., bacterial, fungal, or human immunodeficiency virus \[HIV\], except hepatitis B \[HBV\] and/or hepatitis C \[HCV\], at screening) 4. Evidence of severe retinopathy (e.g., cytomegalovirus retinitis, macular degeneration) or clinically relevant ophthalmological disorder (due to diabetes mellitus or hypertension) 5. History or presence of clinically relevant depression 6. Previous suicide attempts or at any risk of suicide at screening, in the judgement of the Investigator 7. History or presence of clinically significant neurologic diseases 8. History of any malignancy within 5 years (except Stage 0 chronic lymphocytic leukemia, basal cell, squamous cell, and superficial melanoma) 9. History of alcohol or drug abuse within the last year 10. History or evidence of any other MPN 11. History of splenectomy 8. Use of any investigational drug \<4 weeks prior to the first dose of study drug or not recovered from effects of prior administration of any investigational agent 9. Subjects with documented ANA resistance or intolerance (see Appendix 8 for definition).