How Will Ropeginterferon Alfa’s Approval Impact Essential Thrombocythemia?

In a conversation with CancerNetwork®, Ruben Mesa, MD, FACP, president of Advocate Health’s Cancer National Service Line and executive director of the Atrium Health Wake Forest Baptist Comprehensive Cancer Center, spoke about the FDA’s approval of ropeginterferon alfa-2b-njft (BESREMi) for adults with essential thrombocythemia (ET), the first new FDA-approved treatment for the disease in nearly 30 years.¹ The approval was supported by findings from the phase 3 SURPASS-ET trial (NCT04285086), in which ropeginterferon alfa-2b achieved superior durable response rates and reduced thromboembolic events compared with anagrelide (Agrylin) in patients with ET who had progressed on or were intolerant to hydroxyurea.² Ropeginterferon alfa-2b was previously approved for polycythemia vera (PV) in November 2021.³

Mesa, principal investigator of the SURPASS-ET trial, discussed what the approval means for patients, how ropeginterferon and anagrelide compared in the trial, and how ET and PV relate mechanistically. Additionally, he highlighted how he counsels patients on the drug’s safety profile and whether disease-modifying or curative strategies are within reach in the field. He framed the approval as both an immediate win for patients with ET and a foundation for future combination and earlier-line approaches in the disease.

CancerNetwork: What does the FDA approval of ropeginterferon alfa mean for adult patients with ET?

Mesa: The approval of ropeginterferon alfa for these patients is a very important milestone. ET is a chronic leukemia. In the short term, it can carry a risk of blood clots, bleeding, and difficult symptoms, and it can be a progressive disease that can progress on to myelofibrosis, acute leukemia, or, sadly, even patients [dying] if the disease were to really progress. Up to this point, we’ve only had one FDA-approved therapy: anagrelide, which is an isolated platelet-lowering therapy. Ropeginterferon is a major addition. One, it’s the second FDA-approved drug, so there have been limited options. Two, it’s been beneficial in helping to control the [blood] counts in an effective way and having an impact on the underlying clonal disease measured by the impact on the genetics of the disease. We hope this will lead to longer and better outcomes for these patients.

It’s been nearly 30 years since the last new treatment approval for ET. Why has this space moved so slowly compared with other myeloproliferative neoplasms (MPNs), and what changed to finally get a new option across the finish line?

ET is one of the most common MPNs; we estimate maybe 150,000 to 200,000 patients in the US. I think the delay has been, firstly, [due to] a lack of engagement in the development of new therapy for these individuals, which has been unfortunate. Secondly, there’s been a needed advancement in terms of options that were lacking. The JAK inhibitors that have been a major addition for MPNs, overall, had not been very effective at helping to control the significant thrombocytosis that comes with ET. That class, which has been the major class of drugs approved over the past decade, wasn’t overly effective in this scenario.

This approval very much draws off our prior work, showing the impact of long-acting interferons for PV and the FDA approval of ropeginterferon alfa for patients with PV. In many ways, it builds off that experience in a very related disease.

Why was anagrelide chosen as the comparator to ropeginterferon alfa in the SURPASS-ET trial, and how did the 2 agents compare regarding durable response and thromboembolic events?

The current NCCN guidelines, which undoubtedly will be updated after this approval, have hydroxyurea as the approved first-line therapy for patients with ET because, compared with placebo or aspirin, it’s been shown to be superior to doing nothing in the past.⁴ There was also a head-to-head hydroxyurea and anagrelide study in the past, in which hydroxyurea was superior, so that was considered the frontline therapy [while] anagrelide was the second-line therapy. Anagrelide is the only 1 of those 2 that is approved; hydroxyurea is not approved, but is still used in this disease, having been used for a long time in the past. Anagrelide was the natural comparator for the [SURPASS-ET] study population, which was patients with ET who had [progressed on] frontline therapy with hydroxyurea and were then randomly [assigned] to either anagrelide, the current standard of care for second-line therapy, or ropeginterferon alfa, the candidate second-line therapy for these patients.²

What the study demonstrated was that, looking at the overall response, which is control of not only the platelet count but elevated white [blood cell] count if present, [ropeginterferon alfa] was superior for controlling the counts. Additionally, the data favored ropeginterferon alfa as it related to vascular events—blood clotting or bleeding—and as it related to toxicity. It was also superior for molecular impact of the therapy on the disease, as measured by the variant allele frequency of both the JAK2 mutation, which is the most common driver mutation, as well as for calreticulin.

Ropeginterferon already carries an approval in PV. How do its performance and role in ET compare with what you’ve seen in PV? Does that shared mechanism suggest anything about how interferon therapy could unify treatment approaches across MPNs?

In many ways, it does. PV and ET are very much cousins of one another. They overlap extensively for those individuals who have the JAK2 mutation, with some slight differences for those with the calreticulin mutation or the MPL mutation, which are more specific to ET. The long-standing data in PV made us very hopeful that the SURPASS-ET study, the phase 2 EXCEED-ET study [NCT05482971],⁵ and others would be positive, based on the tolerability of the agent, known areas of dosing of the therapy, and the impact on both being able to control counts and decrease the likelihood of vascular events, which is one of the major reasons we treat the disease. [There is also] the improvement of disease-associated symptoms, which were favored with the ropeginterferon arm, as well as its impact on the molecular biology of the disease, the underlying clone.

I use the analogy that both these diseases are treated by therapies that work against the core aspect of the disease itself. These are bone marrow stem cell diseases, and interferon has an impact on that, whereas therapies such as hydroxyurea and anagrelide help diminish the elevation in the blood counts but don’t change the underlying biology of the disease. We’re pleased with the results of the study, but we were very hopeful that these would be exactly the results we’d see based on the experience with the related disease of PV.

How do you counsel patients through ropeginterferon’s safety or risk profile, especially those who may already be wary of a long treatment history with limited options?

One, we have good, long-standing safety data, both from these studies but also from the experience with PV, [and] because these conditions are so similar in many ways. We have a very robust safety profile going into this FDA approval, more so than you might have with a drug that’s first-in-class for a group of disorders. Overall, it’s a well-tolerated drug. The major things we monitor for are rare elevations in liver function tests, rare autoimmune effects that can occur secondarily, and the on-target effect of lowering the blood counts. We clearly adjust the dose accordingly and try to make sure we don’t overshoot in terms of the dose, monitoring the neutrophil count, and others.

Our sweet spot is to try to have individuals with blood counts still in the normal range but adequately controlled to the maximal impact against the disease or the variant allele frequency. What I share with patients is that we monitor [adverse] effects based on regular visits and communication with their healthcare team, and we monitor their blood counts, typically [with] a complete metabolic panel to look at their liver function tests, for any unexpected toxicities.

Looking ahead, do you see a path toward disease-modifying or potentially curative strategies in essential thrombocythemia building on what’s been learned here, or is durable hematologic and thromboembolic control still the realistic ceiling for this disease?

Patients having a good response to ropeginterferon alfa will probably have some degree of disease modification. I think our ability to measure that is still partial. I think there are some individuals who have had tremendous responses to ropeginterferon that we’ll see over time, as we’ve learned in polycythemia vera, where their variant allele frequency might vanish, and there’s evidence of deep disease control. We will achieve some of that, and the more we learn how to best monitor disease progression and disease modification, [the more] we’ll be able to quantify that to a greater degree.

I envision that ropeginterferon may also play an important role in future combination approaches. There are a variety of different approaches [that are] still investigational in essential thrombocythemia, [like] specific agents targeting mutated calreticulin, for example. There’s evolution of JAK inhibitors that could potentially play a role. There’s good reason to think there could be combination approaches; there have been combination approaches in investigational settings of long-acting interferons with JAK inhibitors that have shown some synergistic properties. I suspect that, already, ropeginterferon can be partially disease-modifying, realizing that impact on an individual patient is still a little difficult to exactly quantify. I envision that will build even further over time as we get [a better] understanding of the biology of the disease, as well as the potential approach with different combinations. The approval right now is in this second-line setting, but I think over time we’ll find whether there’s a role for use in earlier phases of the disease, and if so, whether you alter the trajectory even more by using it that early in the disease course.

What do you hope your colleagues take away from this conversation and approval?

I think it’s a big advance to have this therapy now approved for ET. We were very hopeful that these data and these studies would help to broaden the availability of this important therapy for patients with ET and have the impact that we’ve really seen with PV. I think they should be heartened by the fact that there’s been both the time and energy to develop more therapies for this group of patients, as well as how this can be used as a building block for even further approaches in the future that can hopefully aim toward either a truly curative approach, or even further evidence of significant disease modification.

References

1. FDA approves PharmaEssentia’s BESREMi® (ropeginterferon alfa-2b-njft) for adults with essential thrombocythemia, a rare blood cancer. News release. PharmaEssentia USA Corporation. August 31, 2026. Accessed September 2, 2026. https://tinyurl.com/bdnt65xx
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. U.S. FDA approves BESREMi (ropeginterferon alfa-2b-njft) as the only interferon for adults with polycythemia vera. News release. PharmaEssentia Corporation. November 12, 2021. Accessed September 2, 2026. https://bwnews.pr/2YHruCT
4. NCCN. Clinical Practice Guidelines in Oncology. Myeloproliferative neoplasms, Version 2.2026. Accessed September 2, 2026. https://tinyurl.com/3rfmv4np
5. Reeves BN, 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;61:101529. doi:10.1016/j.lana.2026.101529