FDA Approves Ropeginterferon Alfa-2b for Essential Thrombocythemia

The FDA has approved ropeginterferon alfa-2b-njft (Besremi) for the treatment of adult patients with essential thrombocythemia (ET).¹

The decision makes the monopegylated interferon the first new agent approved for the management of ET in the United States since anagrelide (Agrylin) in 1997. The label expansion also follows the November 2021 FDA approval of ropeginterferon alfa-2b for the treatment of adult patients with polycythemia vera.²

The regulatory decision for the ET indication was supported by the phase 3 SURPASS-ET trial (NCT04285086), in which ropeginterferon alfa-2b elicited a modified European LeukemiaNet (ELN) response rate of 42.9% at months 9 and 12 compared with 6.0% for anagrelide (P = .0001) among patients with high-risk ET and resistance or intolerance to hydroxyurea (Hydrea).³ The application was additionally supported by the phase 2b EXCEED-ET trial (NCT05482971), a North American confirmatory study.

What is the mechanism of action of ropeginterferon alfa-2b?

Ropeginterferon alfa-2b is a novel, long-acting, monopegylated interferon-based therapy that achieves cytoreduction alongside a direct anticlonal effect on the malignant clone.² The agent is already approved for the treatment of PV in more than 40 countries worldwide,³ including a recent Health Canada authorization.⁴

ET is a BCR::ABL1-negative myeloproliferative neoplasm frequently associated with mutations in JAK2, CALR, and/or MPL, and is characterized by overproduction of platelets, an increased risk of thrombosis and bleeding, and the potential to progress to myelofibrosis and secondary acute myeloid leukemia.² Standard cytoreductive options have been limited to nonspecific agents, principally hydroxyurea in the first line and anagrelide.²

How was the SURPASS-ET trial designed?

SURPASS-ET was a randomized, phase 3, multicenter, active-controlled, open-label study that enrolled 174 participants across 59 study sites in 8 regions (Canada, China, Hong Kong, Japan, Singapore, South Korea, Taiwan, and the United States).² Eligible patients were 18 years of age or older with a diagnosis of high-risk ET per WHO 2016 criteria, resistance or intolerance to hydroxyurea, and were interferon alfa treatment–naive or anti–ropeginterferon alfa-2b antibody–negative.²

Patients were randomly assigned 1:1 to ropeginterferon alfa-2b administered subcutaneously once every 2 weeks (n = 91) or to oral anagrelide (n = 83), and were stratified by baseline platelet count (at least 800 × 10⁹/L vs less than 800 × 10⁹/L), baseline total symptom score, and country.² Ropeginterferon alfa-2b was titrated from 250 µg at weeks 0 to 2 and 350 µg at weeks 2 to 4 to a fixed dose of 500 µg, while anagrelide was started at its labeled dose and adjusted to maintain optimal blood count control at acceptable toxicity.² The median dose of ropeginterferon alfa-2b over 12 months was 448.6 µg (range, 225-487) once every 2 weeks, and the median dose of anagrelide was 2.0 mg (range, 0.3-4.6) daily.²

The primary end point was the modified ELN response rate at months 9 and 12, a composite requiring a platelet count of 400 × 10⁹/L or less and a white blood cell (WBC) count of less than 9.5 × 10⁹/L, improvement or no progression in disease-related signs such as splenomegaly, improvement or no progression in symptoms by the MPN-SAF total symptom score, and the absence of hemorrhagic or thrombotic events.² Secondary end points included JAK2V617F and CALR allele burden, symptomatic improvement, occurrence of thromboembolic events, and safety.²

At baseline, the median age was 61.0 years (range, 21-80) in the ropeginterferon alfa-2b arm and 64.0 years (range, 20-83) in the anagrelide arm; 51.6% and 53.0% of patients, respectively, were female, and most patients were Asian (94.5% vs 97.6%).² JAK2V617F mutations were present in 79.1% of the ropeginterferon alfa-2b arm and 84.3% of the anagrelide arm, and CALR mutations were present in 12.1% and 12.0%, respectively.²

What additional efficacy data were reported?

Response rates favored ropeginterferon alfa-2b across each individual modified ELN component (P < .0001 for all), including platelet count response (56.0% vs 21.7%), WBC count response (73.6% vs 13.3%), peripheral blood count remission (56.0% vs 6.0%), improvement or non-progression of splenomegaly (87.9% vs 54.2%), symptom response by total symptom score (71.4% vs 33.7%), and absence of hemorrhagic or thrombotic events (84.6% vs 51.8%).²

Reductions in mutational burden also favored the interferon. Mean JAK2V617F allele burden decreased from 33.7% at baseline to 25.3% at 12 months with ropeginterferon alfa-2b (mean change, –8.06) compared with a change from 37.3% to 39.7% with anagrelide (mean change, +3.21).² Mean CALR allele burden changed by –5.32 with ropeginterferon alfa-2b vs –1.45 with anagrelide at 12 months.²

For patient-reported symptoms, a reduction of at least 25% in total symptom score at month 12 was observed in 58.4% of patients treated with ropeginterferon alfa-2b vs 46.5% of those given anagrelide, and a reduction of at least 50% occurred in 53.2% vs 39.5%, respectively.² Major ET-related thrombotic events by month 12 occurred in 1 patient (1.1%) in the ropeginterferon alfa-2b arm vs 8 patients (10.0%) in the anagrelide arm, and major ET-related cardiovascular events occurred in 0 vs 6 patients (7.5%), respectively.²

What is the safety profile of ropeginterferon alfa-2b?

In the safety population, treatment-emergent adverse effects (TEAEs) of any grade occurred in 98.9% of patients who received ropeginterferon alfa-2b (n = 91) and 96.3% of those who received anagrelide (n = 80).² Grade 3 or higher TEAEs were reported in 23.1% vs 33.8% of patients, treatment-emergent serious adverse effects in 14.3% vs 30.0%, and adverse effects of special interest in 27.5% vs 43.8%, respectively.² TEAEs led to dose reductions in 45.1% vs 32.5% of patients and to treatment discontinuation in 5.5% vs 20.0%.² No fatal adverse effects occurred in the ropeginterferon alfa-2b arm, whereas 3 fatal events (3.8%) were reported with anagrelide, comprising 1 case each of acute myocardial infarction, pneumonia, and COVID-19–associated pneumonia.²

The most common any-grade TEAEs with ropeginterferon alfa-2b were increased alanine aminotransferase (31.9%), increased aspartate aminotransferase (31.9%), anemia (27.5%), pyrexia (26.4%), increased beta-2 microglobulin in urine (25.3%), pruritus (22.0%), and decreased weight (20.9%); grade 3 or higher events in these categories were infrequent, each occurring in no more than 1.1% of patients.² The most common any-grade TEAEs with anagrelide were palpitations (32.5%), headache (31.3%), anemia (30.0%), peripheral edema (27.5%), and diarrhea (23.8%).²

Investigators concluded that ropeginterferon alfa-2b demonstrated superior efficacy and a favorable safety profile relative to anagrelide as a second-line treatment for patients with high-risk ET, representing a potential new therapeutic option in a disease with few approved therapies.² [PREWRITE: Add approved-label dosing and any boxed warning or class warnings from the ET prescribing information upon approval.]

References

1. FDA Approves PharmaEssentia’s Besremi (ropeginterferon alfa-2b-njft) for adults with essential thrombocythemia, a rare blood cancer. PharmaEssentia. August 31, 2026. Accessed August 31, 2026. https://www.businesswire.com/news/home/20260831907028/en/FDA-Approves-PharmaEssentias-BESREMi-ropeginterferon-alfa-2b-njft-for-Adults-with-Essential-Thrombocythemia-A-Rare-Blood-Cancer
2. Besremi. Prescribing information. Updated June 2026. Accessed August 18, 2026. https://us.pharmaessentia.com/downloads/Besremi_USPI_ENG.pdf
3. 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. Presented at: 2025 ASCO Annual Meeting; May 30-June 3, 2025; Chicago, IL. Abstract [NOT REPORTED].