Besremi (Ropeginterferon alfa-2b) Safety & Uses | Rx4u

Introduction

Polycythemia vera (PV) is a type of blood cancer where the body makes too many blood cells. Most people with PV carry a change in the JAK2 gene (JAK2V617F), which drives the disease. Having too many blood cells increases the risk of dangerous complications like blood clots, bleeding problems, and, in the long term, progression to more serious conditions such as myelofibrosis or acute leukemia. Managing PV focuses on keeping blood levels under control and lowering the risk of these complications.¹

BESREMi® (ropeginterferon alfa-2b) is a newer treatment option designed to help people living with PV. Unlike older approaches, it works with a unique dosing schedule and has shown effectiveness and safety in studies across different patient groups. It is also the only interferon treatment approved by the US FDA for PV, and it can be used by patients no matter their risk level or previous treatment history. ¹

Background

Ropeginterferon alfa-2b is a new-generation form of interferon, a type of medicine that has been studied for many years in conditions like polycythemia vera (PV) and other related blood disorders. Interferons can help bring blood cell counts back to normal and reduce the risk of complications linked to PV.²

In the past, interferon treatments were difficult for patients because they needed frequent injections and often caused side effects. To make them easier to use, pegylated versions (PEG-interferons) were developed, which last longer in the body and require fewer doses. However, earlier PEG-interferons were not officially approved for treating PV. ²

Ropeginterferon alfa-2b was designed to improve on these earlier versions. It is a “mono-pegylated” interferon, meaning it has a unique structure that helps it stay in the body longer and be more tolerable. This allows it to be given less often while still being effective. Early studies have shown that it works well in patients with PV and is generally better tolerated, making it a promising long-term treatment option. Ropeginterferon alfa-2b has been given orphan drug status by regulators in both the United States and Europe, a recognition reserved for promising treatments for rare diseases like PV. ²

Approved Indications

Ropeginterferon alfa-2b (Besremi) is officially approved by the FDA in the United States for the treatment of adults with polycythemia vera (PV), regardless of their prior treatment or disease risk level. In Europe, the EMA has also approved Besremi for adults with PV, but specifically those without symptomatic splenomegaly (no enlarged spleen causing symptoms).^2,3

Beyond these approvals, ongoing studies are exploring its use for other blood disorders like essential thrombocythemia and myelofibrosis, although these are not yet approved indications.⁴

Mechanism of Action

Most people with polycythemia vera (PV), a chronic blood disorder, carry a change in their DNA known as the JAK2V617F mutation. This “driver mutation” plays a central role in the disease, and reducing its presence in the body is linked with better outcomes, including longer survival and a lower risk of blood clots. Ropeginterferon alfa-2b (BESREMi®), a long-acting form of interferon, has been approved for adults with PV and is now recommended as a preferred first choice for treatment in recent guidelines. Unlike other therapies that act directly on the JAK2 mutation, ropeginterferon works by targeting the abnormal blood cells more broadly, making it effective against the root of the disease process rather than just the mutation itself.⁵

Ropeginterferon attaches to receptors on diseased blood cells and triggers a chain of signals that slow their growth, activate natural tumor-suppressing proteins, and push them into a state where they stop multiplying. This reduces the number of cells carrying the JAK2V617F mutation over time, leading to a lower “allele burden.” Because its action is not limited to JAK2 alone, ropeginterferon may also reduce the impact of other gene changes seen in related conditions like essential thrombocythemia (ET) and primary myelofibrosis (PMF). In this way, it offers a broad and lasting approach to managing myeloproliferative neoplasms. ⁵

Dosing and Administration Overview

Before starting BESREMi, pregnancy testing is recommended for females who are able to become pregnant. For patients who have not previously been treated with hydroxyurea, the recommended starting dose of BESREMi is 100 micrograms, given as a subcutaneous injection every two weeks. The dose can then be increased by 50 micrograms every two weeks, as needed, until blood counts are stabilized.⁶

For patients transitioning from hydroxyurea, BESREMi treatment begins with 50 micrograms given every two weeks, in combination with hydroxyurea. Over the course of Weeks 3 to 12, hydroxyurea is gradually reduced by lowering the total biweekly dose by 20 to 40 percent every two weeks. During this same period, the BESREMi dose is increased by 50 micrograms every two weeks, up to a maximum of 500 micrograms, until blood counts are stabilized. Hydroxyurea should be fully discontinued by Week 13. ⁶

Once the patient reaches stable blood levels, BESREMi should continue at the same two-week interval for at least one year. After stability has been maintained for one year on a consistent dose, the interval may be extended to every four weeks. ⁶

Common Adverse Effects

In clinical studies of BESREMi, some side effects were reported more often than others. Among 178 patients treated for polycythemia vera, the most common reactions (seen in more than 10% of patients) included:⁶

- Increased liver enzymes (20%)

- Low white blood cell count, also called leukopenia (20%)

- Low platelet count, also called thrombocytopenia (19%)

- Joint pain (13%)

- Tiredness or fatigue (12%)

- Muscle pain (11%)

- Flu-like illness (11%)

In the PEGINVERA study with 51 patients, serious side effects were reported in 16% of participants. The most common serious reactions included: ⁶

- Urinary tract infection (8%)

- Transient ischemic attack, or a brief interruption of blood flow to the brain (6%)

- Depression (4%)

Serious Safety Considerations

BESREMi must not be used in people with severe psychiatric illness, allergy to interferons, moderate or severe liver disease, serious or untreated autoimmune disease, or in transplant patients on immunosuppressive therapy. ⁶

Patients may develop depression, thyroid or blood sugar problems, and heart issues. BESREMi can lower blood counts, increasing infection or bleeding risk, so regular tests are needed. Serious allergic reactions may occur. Other risks include pancreatitis, colitis, lung, eye, kidney, dental, and skin problems. The medicine may cause dizziness, so driving should be avoided until effects are known. BESREMi can harm an unborn baby; pregnancy testing and contraception are required.⁶

Close monitoring is essential during treatment. Complete blood counts should be performed every two weeks during the titration phase and then every three to six months once the optimal maintenance dose has been established. In some cases, phlebotomy may be required during the titration phase to manage increased blood thickness. If treatment is interrupted, dosing should be resumed at the previously reached level. In cases of drug-related side effects, the dose should be reduced to the next lower level or paused according to the provided guidance. If the lower dose does not provide sufficient benefit, an attempt may be made to return to a higher dose once side effects have improved.⁶

Clinical Evidence

Clinical evidence from the PROUD-PV and CONTINUATION-PV trials has shown that Ropeginterferon alfa-2b provides sustained and meaningful benefits for patients with polycythemia vera.⁷

Over long-term follow-up, Ropeginterferon alfa-2b demonstrated higher complete hematologic response rates (54.6% vs. 34.9%) and molecular responses (66.0% vs. 19.4%) compared to control treatment. After six years, patients receiving Ropeginterferon alfa-2b reported fewer symptoms (15.7% vs. 20.7%) and the majority, 81.4%, were able to maintain hematocrit levels below 45% without the need for phlebotomy, compared to 60.0% in the control group. Importantly, disease progression was slowed, with JAK2 V617F allele burden reduced to below 1% in 20.7% of patients treated with Ropeginterferon alfa-2b versus only 1.4% of those in the control arm, and event-free survival was significantly higher. ⁷

Ropeginterferon alfa-2b also showed good long-term tolerability, with only 10% of patients discontinuing due to drug-related events over at least five years, lower than with other interferons. Benefits were sustained both in hydroxyurea-naive patients and those previously treated, supporting the role of Ropeginterferon alfa-2b not only as an early therapy but also in second-line and later settings.

Overall, long-term data confirm that Ropeginterferon alfa-2b achieves the key goals of PV therapy, including durable response, improved quality of life, slowed disease progression, and favorable safety. ⁷

Conclusion

Besremi (Ropeginterferon alfa-2b) is an important treatment option for people living with polycythemia vera. With its unique dosing schedule and growing body of evidence, it offers a long-term approach that can help manage this rare blood condition.

Note:

The information provided is for education purpose only and is subjected to prescribing information of the drug and the guidance of your treating physician. Always consult your health care provider before making any medical decision for starting your treatment.

Disclaimer:

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References

- Suo SS, Fu RF, Qin A, et al. Effective Management of Polycythemia Vera With Ropeginterferon Alfa-2b Treatment. J Hematol. 2024;13(1-2):12-22. doi:10.14740/jh1245

- Gisslinger H, Zagrijtschuk O, Buxhofer-Ausch V, et al. Ropeginterferon alfa-2b, a novel IFNα-2b, induces high response rates with low toxicity in patients with polycythemia vera. Blood. 2015;126(15):1762-1769. doi:10.1182/blood-2015-04-637280

- European Medicines Agency. Besremi (ropeginterferon alfa-2b). EPAR – Public Assessment Report. EMA. Published May 8, 2019. Updated April 9, 2025. https://www.ema.europa.eu/en/medicines/human/EPAR/besremi

- 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