"In polycythemia vera, 10–20% of patients develop resistance or intolerance to hydroxyurea treatment. Since no other treatment option is available, reimbursement for the new treatment option must be considered."

Although the average survival for polycythemia vera is around 14.1 years, typically considered a comparatively lower mortality risk than other blood cancers, the abnormal overproduction of blood cells in the bone marrow can lead to severe cardiovascular complications such as thrombosis and embolism.

Currently, the disease cannot be completely cured, and long-term management of complications is of utmost importance. However, treating the disease with the standard therapy hydroxyurea is limited because of its non-responsiveness or intolerance.

Dr. Seong Yoon Yi, Professor of the Division of Hematology-Oncology in the Department of Internal Medicinea at Inje University Ilsan Paik Hospital, emphasized the critical need to secure reimbursement for new treatment options that target the underlying pathology of polycythemia vera.

Polycythemia vera is caused by somatic mutations in the bone marrow that abnormally activate hematopoiesis, resulting in excessive production of red blood cells, white blood cells, and platelets. Approximately 90% of patients with polycythemia vera have been found to harbor a mutation in the JAK2 gene.

Dr. Lee explained, "Because polycythemia vera is a rare blood cancer, it is uncommon for patients to seek medical attention in its early stages. Most patients are diagnosed only after presenting with vague symptoms, followed by blood tests, bone marrow examinations, and genetic tests."

Dr. Lee said treatment strategies are typically divided into low-risk and high-risk groups. Patients aged 60 or older or those with a history of thrombosis are classified as high-risk.

Low-risk patients are generally treated with aspirin and phlebotomy, whereas high-risk patients receive these interventions in combination with hydroxyurea to help control excessive blood cell production.

The problem with polycythemia vera, being an incurable condition requiring prolonged treatment, is the emergence of drug tolerance and adverse effects.

Dr. Lee explained, "Polycythemia vera, like diabetes and hypertension, is a chronic condition that requires lifelong management, which means treatment lasts indefinitely," adding, "Over the long term, there are instances when blood counts are not stably controlled with hydroxyurea, and the disease can progress rapidly."

"In some cases, patients develop tolerance to hydroxyurea so that it no longer provides therapeutic benefits, or they experience intolerable side effects that force them to discontinue treatment," He added. "Typical side effects include skin ulcers, a decrease in white blood cell counts leading to compromised immunity, and a decline in cardiac function, especially in older patients."

Patient Lee Deok-hee, who joined the meeting with Dr. Lee, shared, "Since my diagnosis in 2010, I have been receiving both hydroxyurea and phlebotomy for 13 years. Initially, having hydroxyurea prescribed every three months was enough to maintain stable blood counts. However, since 2023, as I've developed resistance, I've had to visit the emergency room more frequently, and my daily life has become so restricted that I can no longer maintain my work."

"Polycythemia vera's second-line treatment option poses a cost problem"

According to research from the Myeloproliferative Neoplasms Research Group under the Korean Society of Hematology, approximately 10–20% of polycythemia vera patients develop resistance or intolerance to hydroxyurea treatment.

Regarding this, Dr. Lee emphasized, "Although polycythemia vera is considered a rare blood cancer and may appear to affect only a small patient population, the number of cases continues to accumulate over time. As the disease progresses, low-risk patients often transition to a high-risk category, thereby increasing the likelihood of developing resistance or intolerance, presenting a challenge that cannot be overlooked."

Following hydroxyurea treatment, two treatment options are considered: Besremi (ropeginterferon alfa-2b) and Jakavi (ruxolitinib).

Besremi is a next-generation interferon that selectively targets and eliminates the JAK2 mutation, the primary cause of polycythemia vera. It was developed to improve the purity and tolerability compared to existing interferons, allowing for administration every two weeks for the initial 1.5 years and once every four weeks thereafter.

Currently, Besremi is recommended as a polycythemia vera treatment in the National Comprehensive Cancer Network (NCCN) and European Leukemia Network (ELN) guidelines, regardless of a patient's prior treatment history.

"Notably, the extent to which the allelic burden, which is the fundamental driver of the disease, is reduced," Dr. Lee said. "Clinical trials have demonstrated that Besremi significantly lowers the JAK2 mutation allelic burden. This means that Besremi alleviates symptoms and addresses the underlying cause of polycythemia vera."

However, Besremi and Jakavi are currently not reimbursed, posing substantial cost hurdles. In practical terms, hydroxyurea remains the only treatment that patients can use without an economic burden.

Consequently, there is growing attention on Besremi's multiple attempts to be considered for the Economic Evaluation Committee of Health Insurance Review and Assessment Service (HIRA).

Given the apparent demand for new treatment options in clinical practice, industry observers are closely watching whether Besremi can pass through the subcommittee review and ultimately reach the final stage at the Drug Reimbursement Evaluation Committee (DREC).

Dr. Lee said, "We know that patients with polycythemia vera want new treatment options to be reimbursed. In particular, Besremi has shown stable clinical data across risk groups and offers the potential for a fundamentally transformative approach, which has greatly raised patient expectations."

He added, "While it would be ideal for every patient to access treatment without any economic burden, the realities of the National Health Insurance budget mean that securing reimbursement is especially urgent for patients who develop resistance or intolerance to hydroxyurea. These patients have no other treatment options once hydroxyurea becomes ineffective."

Finally, Dr. Lee stressed that, given the unique characteristics of polycythemia vera as a rare blood cancer, reimbursement reviews should consider not only the number of patients and drug costs but also the broader societal burden.

"Costs related to treating side effects of hydroxyurea, such as myocardial infarction or stroke, and the social costs when caregivers have to quit their jobs for patient care are often overlooked. I hope these factors will be partially reflected in the drug reimbursement decision-making process," Dr. Lee added.