Ropeginterferon alfa-2b (BESREMi) is a novel, mono-pegylated, long-acting interferon alfa-2b that is FDA-approved for the treatment of adults with polycythemia vera (PV), regardless of thrombotic risk level or treatment history.
It is an innovative interferon that targets the source of the disease, modifying its progression rather than just treating symptoms.
Primary: Polycythemia vera (PV)—a slow-growing blood cancer that causes the bone marrow to make too many red blood cells.
It is approved for PV regardless of its risk level or prior treatment history.
It is also emerging as a disease-modifying therapy for other myeloproliferative neoplasms (MPNs), including essential thrombocythemia (ET) and early myelofibrosis.
Subcutaneous injection.
Dosing
Treatment-naive patients: Starting dose 100 mcg subcutaneously every 2 weeks, increased by 50 mcg increments every 2 weeks (maximum 500 mcg) until hematological stabilization.
Transitioning from hydroxyurea: Starting dose 50 mcg every 2 weeks.
After at least 1 year of stable dosing every 2 weeks, the interval may be extended to every 4 weeks.
Contraindications:
It should not be used by individuals with severe psychiatric conditions, a history of severe depression, active autoimmune diseases, or a history of severe heart disease.
Side Effects: Common side effects include low platelets and white blood cells, joint and muscle pain, fatigue, flu-like symptoms, itching, and elevated liver enzymes.
Because it is an interferon, it may cause or worsen autoimmune, ischemic, neuropsychiatric, and infectious disorders.
Ropeginterferon alfa-2b binds to the interferon alfa receptor (IFNAR), activating a downstream signaling cascade through JAK1, TYK2, and STAT proteins, which controls gene-expression programs that exert antiproliferative and immunomodulatory effects on malignant hematopoietic cells.
It consists of a single positional isomer (unlike conventional pegylated interferons with multiple isomers), resulting in a longer elimination half-life and improved tolerability.
A higher initial dose and accelerated titration (HIDAT) regimen (250 mcg-350 mcg-500 mcg) has been used in clinical trials for ET and myelofibrosis with good tolerability.
PROUD-PV/CONTINUATION-PV phase 3 trial, ropeginterferon alfa-2b demonstrated superiority over hydroxyurea in achieving durable hematological and molecular remissions in PV, with increasing response rates over time (up to 3 years), while hydroxyurea responses declined.
In low-risk PV, ropeginterferon with phlebotomy achieved hematocrit control in 81.3% vs. 59.7% with phlebotomy alone and was associated with 0% disease progression vs. 12.7% in the comparator group.
A phase 2 study in early myelofibrosis (pre-fibrotic and lower-risk fibrotic) demonstrated clinical hematological complete response in 70% at week 104, with JAK2 V617F allele burden reduction in ~68% and bone marrow fibrosis reduction in 26% of evaluable patients.
Molecular Response: has the ability to achieve progressive reduction in JAK2 V617F allele burden, and emerging data show reduction in CALR mutant allele burden as well.
This molecular response raises the possibility of true disease modification, potentially reducing the risk of progression to myelofibrosis or acute leukemia.
Adverse Effects and Monitoring
Common adverse effects include headache, injection site reactions, elevated ALT, peripheral neuropathy, flu-like symptoms, and neutropenia (grade 3 4-9%).
Key monitoring requirements:
Screening for psychiatric history (depression) and ongoing mood monitoring
Monitoring for autoimmune disorders
Thyroid function at baseline and annually
Liver enzymes at baseline and during treatment
Baseline eye examination, with periodic exams in patients with preexisting ophthalmologic conditions
Ropeginterferon should be avoided in patients with clinically significant depression/anxiety or severe untreated autoimmune diseases.
Immunogenicity was low, with anti-drug antibodies detected in only 1.4% of subjects across pivotal trials, and no neutralizing antibodies were observed.