Ropeginterferon Alfa-2b Yields Durable Responses in Essential Thrombocythemia

Results from the pivotal phase 3 SURPASS-ET trial (NCT04285086), first released in January 2025 and newly published in The Lancet Haematology, highlight durable responses by ropeginterferon alfa-2b-njft (Besremi) in patients with hydroxyurea-intolerant or -refractory essential thrombocythemia (ET) with leukocytosis.^1,2

Notably, the trial met its primary end point, yielding durable clinical responses per modified European Leukemia Net criteria. At months 9 and 12, ropeginterferon alfa-2b boasted superior responses to anagrelide (Agrylin), the standard second-line therapy in the event of intolerance or resistance to first-line hydroxyurea therapy (43% vs 6%). This difference of 36.5% was statistically significant (95% CI, 25.4%–47.7%; P =.0001).

The agent also demonstrated a tolerable safety profile that was largely favorable relative to anagrelide. Patients in the ropeginterferon alfa-2b group experienced a lower rate of grade 3 or worse treatment-emergent adverse events compared with those in the anagrelide group (23% vs 34%). No treatment-related deaths occurred in either group.

According to investigators, these results support the agent’s therapeutic potential in the second line for patients with ET and leukocytosis.

"The SURPASS-ET data are impressive and demonstrate not only durable clinical and symptomatic benefits with ropeginterferon alfa-2b, but also reductions in JAK2 V617F allele burden—an important marker associated with potential disease modification," Ruben Mesa, MD, Atrium Health and Wake Forest Baptist Comprehensive Cancer Center, said in a news release.¹ "ET remains a challenging chronic disease, and patients who are resistant or intolerant to hydroxyurea have had few alternatives for sustained disease control. After nearly [3] decades without new therapeutic options, these findings represent a promising step forward for patients and clinicians."

About Ropeginterferon Alfa-2b

Ropeginterferon alfa-2b is a next-generation interferon-based therapy. The agent, approved by the FDA in 2021, is indicated for the treatment of adults with polycythemia vera (PV) and is a recommended treatment for myeloproliferative neoplasms (MPNs) and, more specifically, first-line, low-risk PV under the National Comprehensive Cancer Network guidelines.

Although the agent has been included in treatment guidelines for PV, it has not been approved by the FDA for ET.

“Long-acting interferons are clearly active in treating ET, impacting MPN stem cell and mutant allele burden. Although long-acting interferons are in our guidelines, they are not yet FDA approved [for ET]. This crucial phase [3] trial is essential for confirming the efficacy and safety of ropeginterferon alfa-2b-njft for ET, and hopeful[ly] broaden[ing] availability for patients in ET as it has for PV," Mesa explained in a previous interview with Targeted Oncology.

With the positive results of the phase 3 trial, PharmaEssentia, trial sponsor, has begun to pursue label expansion to include ET with submission of a supplemental biologics license application to the FDA.

"Ropeginterferon alfa-2b-njft has already reshaped the treatment landscape for [PV], and the findings from this study further reinforce its potential to benefit patients across the MPN spectrum,” Ko-Chung Lin, PhD, CEO of PharmaEssentia, said in the news release.¹ “We look forward to advancing our regulatory efforts to bring this therapy to individuals living with ET, supporting the potential to expand our commercialization efforts in this new indication in 2026, pending FDA approval."

Trials of Ropeginterferon Alfa-2b in ET

The phase 3 SURPASS-ET trial is a randomized, open-label, multicenter study designed to evaluate the efficacy, safety, and tolerability of ropeginterferon alfa-2b vs anagrelide in second-line ET.^2,3 The study’s primary end points include peripheral blood count remission, improvement or nonprogression in disease-related signs; large symptoms improvement or maintenance of nonprogression; and absence of hemorrhagic or thrombotic events.

Here, 174 patients were randomly assigned to receive either 250 to 500 µg of ropeginterferon alfa-2b by subcutaneous injection once every 2 weeks (n = 91) or 0.5 mg of anagrelide daily (n = 83).

Parallel to the phase 3 trial, the safety of ropeginterferon alfa-2b in patients with ET is also being explored in the single-arm, phase 2b EXCEED-ET study (NCT05482971).

REFERENCES

1. PharmaEssentia announces publication of phase 3 SURPASS-ET results in The Lancet Haematology. News release. PharmaEssentia. November 24, 2025. Accessed November 25, 2025. https://tinyurl.com/3yrpkbae

2. 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;12(11):e862-e875. doi:10.1016/s2352-3026(25)00264-9

3. Ropeginterferon alfa-2b (P1101) vs. anagrelide in essential thrombocythemia patients with hydroxyurea resistance or intolerance (SURPASS-ET). ClinicalTrials.gov. Updated August 13, 2025. Accessed November 25, 2025. https://clinicaltrials.gov/study/NCT04285086