Start With FIRST-LINE BESREMi Pen for Patients With PV Requiring Cytoreductive Therapy: From Clinical Results to Real-World Practice

Welcome. Today, we will explore long-term management of polycythemia vera with BESREMi, reviewing its clinical evidence and practical administration. 

I’m Beth Faiman. I’m a nurse practitioner from Cleveland, Ohio, and I’m proud to be here today.

During today’s session, we will first present an overview of PV and discuss BESREMi as a treatment option for PV and its mechanism of action. Then, we will delve into the clinical trial data for BESREMi and go over BESREMi’s new route of administration.

PV is a progressive and potentially life-threatening chronic blood cancer. PV is a chronic myeloproliferative neoplasm, presenting with significant symptom burden, thrombohemorrhagic complications, and reduced survival.

The prevalence of PV is ~50 cases per 100 000 people with an incidence of 1 to 3 cases per 100 000 annually.

The median age at diagnosis is 61 years, and the median survival is 15 years.

So, PV begins in the bone marrow, with a JAK2 mutation in hematopoietic stem cells (or HSCs).

Mutated HSCs drive overproduction of red blood cells, white blood cells, and platelets.

Symptoms include fatigue, pruritus, and symptomatic splenomegaly.

There’s an increased risk of thrombotic events, potentially an evolution to myelofibrosis, and acute myeloid leukemia (or AML).

The diagnosis of PV requires the integration of clinical and laboratory findings, bone marrow morphologic features, and JAK2 analysis.

The 2016 update to the World Health Organization diagnostic criteria for PV included the addition of characteristic bone marrow morphology as 1 in 3 major diagnostic criteria, which allowed reduced hemoglobin and hematocrit threshold for diagnosis.

PV begins with a mutated stem cell expressing JAK2 mutations in the bone marrow, often occurring years prior to a diagnosis of PV.

PV is characterized by the proliferation of mutated hematopoietic stem cells.

PV affects 3 main blood cell lines. Patients experience and clinically present with excessive levels of red blood cells, white blood cells, and platelets.

Because the disease is progressive, these mutated HSCs acquire a selective advantage that favors their proliferation over normal hematopoietic stem cells.

It is important to understand that PV starts in the bone marrow and that the mutated stem cell is the root cause of the disease.

The mutated stem cell undergoes clonal expansion, continuously giving rise to new clones that expand and crowd out healthy cells.

Over time, this leads to an inflamed bone marrow microenvironment that supports the proliferation of more mutated hematopoietic stem cells.

Patients remain at risk because this clonal activity in the bone marrow.

The short-and long-term consequences in PV extend beyond high hematocrit.

Clonal expansion of the HSCs affects 3 cell counts, fosters inflammation that contributes to further disease development, and contributes to a disordered bone marrow microenvironment.

These factors mean that patients have a 40% increased risk of cardiovascular disease, such as thrombosis, accelerated atherosclerosis, heart attack, stroke, or heart failure—short-term risks we are all familiar with.

PV is a long-term progressive disease, and patients also face long-terms risks of hematologic malignancies.

In the myeloproliferative neoplasms landmark patient study, patients reported that their most important treatment goal was to “slow or delay progression of the condition,” followed by prevention of vascular/thrombotic events, healthy blood counts, better quality of life, symptom improvement, and hematocrit levels of <45%.

Treatment considerations for patients with PV should focus on the long-term risks of the disease.

Boxed Warning

WARNING: RISK OF SERIOUS DISORDERS

Interferon alfa products may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations. Therapy should be withdrawn in patients with persistently severe or worsening signs or symptoms of these conditions. In many, but not all cases, these disorders resolve after stopping therapy.

BESREMi is an innovative and long-acting interferon alfa-2b that works in the bone marrow.

In nonclinical studies, BESREMi has been shown to specifically target interferon alfa receptors on mutant stem cells.

This provides prolonged release due to its novel pharmacokinetic properties, which results in BESREMi having a half-life and clearance of approximately 7 days. This allows for once-every-2-weeks dosing, which may be expanded to 1 dose every 4 weeks after hematologic parameters have been stable for at least 1 year.

BESREMi targets the source of PV in the bone marrow to address the underlying disease.

Next, let’s review the clinical trial data that supported BESREMi’s approval as a treatment option for PV. 

The PEGINVERA study was a prospective, open-label, single-arm, 2-stage study, conducted in 6 sites in Austria to determine the maximum tolerated dose with a cohort expansion to look at safety and efficacy in patients with PV.

PEGINVERA continued for a total of 7.5 years of follow-up and evaluated the maximum tolerated dose, efficacy and safety, and pharmacokinetic parameters of BESREMi in patients diagnosed with PV.

Patients who were diagnosed, pretreated with hydroxyurea (HU)/phlebotomy, and patients currently on HU but who were unable to control hematocrit or persistent PV symptoms were included in the study.

HU-pretreated patients were defined as patients treated with HU at the time of enrollment until switched to BESREMi.

Patients were excluded if they were diagnosed with another myeloproliferative disorder, were previously treated with another interferon alfa for PV, had concurrent treatment with cytoreductive agents other than HU or investigational agents of any type, had clinically significant history or known presence of psychiatric disorders, and/or had severe concomitant comorbidity, including autoimmune disease.

Doses in stage 1 varied from 50 mcg to 540 mcg, while patients in stage 2 started at 150 mcg and were titrated up appropriately. Because of formulation changes, the recommended starting dose, titration amounts, and maximum dose of BESREMi differ slightly from those used in the clinical trial.

The median duration of treatment exposure was 61 months.

BESREMi (ropeginterferon alfa-2b) was initiated in patients diagnosed with PV regardless of time from diagnosis, age, prior cytoreductive therapy, and cardiovascular history.

The mean age of patients in PEGINVERA was 56 years, with a range of 35 to 82 years and a median duration of PV from diagnosis of 2.2 years.

Seventeen, or 33% of patients, received prior treatment with HU. 

Eight, or 16% of patients, were newly diagnosed.

Two-thirds of patients with an n of 34 over 51 were HU-naïve.

Twenty-two percent of patients had a prior history of major cardiovascular events.

Cardiovascular events included pulmonary embolism, stroke, myocardial infarction, and portal vein thrombosis.

A robust hematologic response (based on hematocrit, leukocytes, and platelets) was achieved by a majority of patients taking BESREMi over 7.5 years, with an overall hematologic response rate of 80%. The median duration of this response was 20.8 months, with a 95% confidence interval of 13.0 to 43.8.

A comprehensive disease control (hematocrit level of <45% without phlebotomy in the past 2 months, leukocytes of ≤10 x 10⁹/L, and platelets of ≤400 x 10⁹/L, normal spleen size, and absence of thromboembolic events) was achieved by a majority of patients being treated with BESREMi over the study duration, with an overall response rate of 61%.

Patients on BESREMi may experience a response in as early as 10 weeks.

About 27% of patients in the PEGINVERA trial achieved comprehensive disease control at 10 weeks on BESREMi.

About 44% of patients in the trial achieved a partial response at 10 weeks on BESREMi, which is defined as hematocrit of <45% without phlebotomy but with persistent splenomegaly or elevated (>400x10⁹/L) platelet count, or reduction of phlebotomy requirements by at least 50%.

The median time to respond was 7.8 months for the 61% of patients who achieved a comprehensive disease control. As was done in the clinical trials, phlebotomies should be administered as needed during the dose-escalation phase to mitigate short-term risks.

The most common reported adverse events, defined as treatment-emergent adverse events throughout the treatment period of 7.5 years, were influenza-like illness, arthralgia, fatigue, and pruritus.

The majority of adverse reactions were grade 1/2, with a small percentage of grade 3/4 adverse reactions, including influenza-like illness, depression, diarrhea, and thrombocytopenia.

BESREMi-related adverse reactions were generally mild, transient, and declined over time.

In the 7.5-year PEGINVERA study, 95% of the BESREMi-related adverse reactions observed were grades 1 or 2.

Nearly 40% of the BESREMi-related adverse events occurred in the first 3 months of treatment on BESREMi.

Zero cases of AML and 1 case of myelofibrosis were observed in 7.5-year analysis of the PEGINVERA study.

There are additional robust data supporting BESREMi’s role as first-line treatment option for PV at besremihcp.com.

BESREMi Pen is now available for patients.

Designed for simpler self-administration, BESREMi Pen helps patients deliver the prescribed dose every time.

The pre-filled syringe will no longer be commercially available on October 1.

BESREMi should be titrated until hematologic parameters are stabilized.

BESREMi is administered as 1 subcutaneous injection every 2 weeks.

In patients not already on HU, the starting dose is 100 mcg every 2 weeks.

Increase the dose by 50 mcg every 2 weeks until all hematologic parameters (hematocrit, white blood cells, and platelets) are stabilized and up to a maximum dose of 500 mcg.

Patients should be titrated to the dose level at which hematologic parameters are stabilized (hematocrit <45%, leukocytes <10 x 10⁹/L, and platelets <400 x 10⁹/L).

During the PEGINVERA study, all eligible patients (n=28) switched to 1 dose every 4 weeks after hematologic stability had been achieved for at least 1 year on BESREMi. The mean dose of BESREMi was 237 mcg (±110) during the treatment period.

In patients transitioning from hydroxyurea, the starting dose is 50 mcg every 2 weeks.

Increase the dose by 50 mcg every 2 weeks until all hematologic parameters (hematocrit, white blood cells, and platelets) are stabilized and up to a maximum dose of 500 mcg.

Patients should be titrated to the dose level at which hematologic parameters are stabilized (hematocrit <45%, leukocytes <10 x 10⁹/L, and platelets <400 x 10⁹/L). Reduce the total biweekly dose of hydroxyurea by 20% to 40% during Weeks 3 to 12, to discontinue HU by Week 13.

During the PEGINVERA study, all eligible patients (n=28) switched to 1 dose every 4 weeks after hematologic stability has been achieved for at least 1 year on BESREMi. The mean dose of BESREMi was 237 mcg (±110) during the treatment period.

Hematologic stability is defined as hematocrit <45%, leukocytes <10 x 10⁹/L, and platelets <400 x 10⁹/L.

Monitor complete blood count every 2 weeks during the titration phase and dose modification phase, and every 3 to 6 months during the maintenance phase (after the patient’s optimal dose is established). Monitor complete blood count more frequently if clinically indicated.

Phlebotomy as a rescue treatment to normalize blood hyperviscosity may be necessary. If dose interruption occurs, resume dosing at previously attained levels. If drug-related toxicities arise, reduce the dose to the next lower level or interrupt in accordance with the prescribing information.

If there is insufficient efficacy at the decreased dose following dose modification, a dose increase attempt to the next higher dose level should be considered after recovery to grade 1 toxicity.

I’d now like to recap what was discussed:

BESREMi targets PV in the bone marrow to alter the course of the disease. Durable blood count control with 0 cases of AML and 1 case of MF were observed over the 7.5-year clinical trial.

In the 7.5-year clinical trial, BESREMi demonstrated a robust hematologic response rate of 80% and comprehensive disease control with 0 thromboembolic events. It showed a manageable safety profile with the vast majority of adverse reactions grade 1 or 2.

Ropeginterferon alfa-2b is also a preferred first-line cytoreductive therapy option for both symptomatic low-risk and high-risk PV in the NCCN Clinical Practice Guidelines in Oncology® for Myeloproliferative Neoplasms.

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21. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Myeloproliferative Neoplasms V.1.2026. © National Comprehensive Cancer Network, Inc. 2026. All rights reserved. Accessed May 21, 2026. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.