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FDA approves ropeginterferon alfa-2b for adult patients with essential thrombocythemia

On 30 August, 2026, the U.S. Food and Drug Administration (FDA) approved ropeginterferon alfa-2b-njft for adult patients with essential thrombocythemia (ET), expanding its use beyond its existing indication in polycythemia vera (PV).1 The FDA decision follows the submission of a supplemental Biologics License Application (sBLA) earlier this year, supported by data from the SURPASS-ET (NCT04285086) and EXCEED-ET (NCT05482971) clinical trials.2

ET is a chronic Philadelphia chromosome-negative myeloproliferative neoplasm (MPN) characterized by clonal overproduction of platelets, most commonly driven by mutations in JAK2, CALR, or MPL.3 Although many patients have an indolent disease course, ET is associated with potentially serious thrombotic and hemorrhagic complications, as well as constitutional symptoms and, over time, a risk of progression to myelofibrosis or acute myeloid leukemia (AML).3

For patients requiring cytoreduction, hydroxyurea and anagrelide have been the mainstay of treatment; however, a proportion of patients cannot tolerate or do not adequately respond to these therapies, highlighting a need for additional treatment options.4 Furthermore, conventional cytoreductive therapies primarily control hematologic parameters and thrombotic risk rather than directly targeting the underlying malignant clone and modifying the disease course.4 

Ropeginterferon alfa-2b (ropeg) is a monopegylated formulation of interferon alfa-2b designed to provide prolonged exposure and enable subcutaneous administration every 2–4 weeks.4 It has consistently demonstrated hematologic and molecular activity in PV, providing the biological rationale for its development in ET. 

The pivotal evidence for the approval of ropeg comes from SURPASS-ET, a global, open-label, randomized Phase III trial evaluating ropeg versus anagrelide in patients with second-line high-risk ET who are resistant or intolerant to hydroxyurea.5 A total of 174 patients were randomized to anagrelide (n=83) or ropeg (n=91), the latter of which was dosed subcutaneously every 2 weeks (starting at 250 μg, titrated to 350 μg at Week 2, and 500 μg from Week 4 onward).5 The study met its primary endpoint, with ropeg treatment leading to a significantly higher response rate at Months 9 and 12, as per modified European LeukemiaNet (ELN) criteria (42.9% versus 6.0% for anagrelide; 95% CI: 25.4-47.7; p<0.0001).5 Ropeg also demonstrated greater control of platelet and white blood cell counts, fewer major thrombotic events, and an improvement or stabilization of both symptoms and splenomegaly.6 Additionally, reductions were observed in the mean JAK2 V617F allelic burden from baseline to 12 months, pointing towards a potential disease-modifying effect of the therapy.6 The safety profile of ropeg was favorable relative to anagrelide; Grade ≥3 adverse events (AEs) occurred in 23.1% of patients receiving ropeg compared with 33.8% receiving anagrelide, while serious AEs occurred in 15.4% and 30.0% of patients, respectively.5 Treatment discontinuation due to AEs was also less frequent with ropeg (5.5% versus 20.0% in the anagrelide arm).5

Additional supportive evidence for the approval comes from the EXCEED-ET study, a North American, single-arm Phase IIb trial enrolling 91 patients, both treatment-naïve and those previously exposed to hydroxyurea. A durable modified ELN response rate at Months 10 and 13 was observed in 60.2% of patients (95% CI: 49.0–71.4), with a median time to hematologic response of 8.4 weeks (95% CI: 8.1–11.9).7 Responses were accompanied by improvement or stabilization of splenomegaly and symptoms in 98.9% and 78.0% of patients, respectively.7 Molecular responses were observed across JAK2, CALR, and MPL-mutated disease, supporting activity across different molecular subtypes.7 In general, the tolerability of treatment was favorable. Grade ≥3 treatment-emergent AEs were reported in 27.5% of patients, and ropeginterferon-related discontinuations occurred in 9.9% of patients.7

At the 31st Congress of the European Hematology Association (EHA 2026), we spoke with Lucia Masarova, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, who discussed how ropeginterferon alfa-2b could reshape the therapeutic landscape of ET and where it may fit in the treatment paradigm. Dr Masarova states: “So although SURPASS-ET showed great efficacy and superiority…of [ropeginterferon alfa-2b] over anagrelide…the EXCEED-ET study showed efficacy in frontline patients. So that could actually help establish where you use interferon in patients with ET, which actually, definitely, we see a second-line role… but we also see a role broadly in patients in need of therapies regardless of the lines.”

The label expansion of ropeginterferon alfa-2b represents the first new FDA-approved treatment for ET in almost three decades and provides a new cytoreductive option for a disease in which treatment has historically focused primarily on controlling blood counts and reducing thrombotic risk.6 Longer-term follow-up will be important to determine whether reductions in driver mutation burden translate into meaningful effects on disease progression and vascular events, and to clarify how this agent should be sequenced alongside established and emerging cytoreductive therapies.

References

  1. FDA Approves Treatment for Essential Thrombocythemia. Available here. (Last Accessed 03/09/2026).
  2. PharmaEssentia. FDA confirms a PDUFA goal date of August 30, 2026 for the sBLA submission of ropeginterferon alfa-2b-njft in essential thrombocythemia. Available here. (Last accessed 07/07/2026) 
  3. Kiladjian JJ, Marin FF, Al-Ali HK, et al. ROP-ET: a prospective phase III trial investigating the efficacy and safety of ropeginterferon alfa-2b in essential thrombocythemia patients with limited treatment options. Ann Hematol. 2024 Jul;103:2299-2310. 
  4. Mesa R, Gill H, Zhang L, et al. Ropeginterferon alfa-2b in hydroxyurea-intolerant or hydroxyurea-refractory essential thrombocythaemia (SURPASS ET): a multicentre, open-label, randomised, active-controlled, phase 3 study. Lancet Haematol. 2025 Nov;12:e862-e875. 
  5. Mesa R, Gill H, Xiao Z, et al. Ropeginterferon alfa-2b versus anagrelide for the treatment of essential thrombocythemia: Topline results of the phase 3 SURPASS-ET trial. Abstract 6500. Presented at the 2025 ASCO Annual Meeting; May 29–June 02, 2025; Chicago, IL. 
  6. Reeves B, El Chaer F, Foltz L, et al. Ropeginterferon alfa-2b-njft treatment in essential thrombocythemia across different driver mutations: results from a North American, single-arm, multicentre study (EXCEED-ET). Lancet Reg Health Am. 2026 Jun;61:101529.

Written by Natalie Markova

Reviewed by Anya Dragojlovic Kerkache