Besremi® (ropeginterferon alfa-2B)
PharmaEssentia, AOP Orphan Pharmaceuticals
Mono-pegylated proline interferon
Approved in Europe
Besremi® (ropeginterferon alfa-2B) is a mono-pegylated proline interferon indicated for the treatment of polycythaemia vera. It is one of the first of its kind to be approved for the condition.
Developed by PharmaEssentia, the drug received orphan medical product designation from the European Medicines Agency (EMA) in December 2011. It has also received orphan drug designation in the US.
The EMA’s Committee for Medicinal Products for Human Use (CHMP) gave a positive opinion for the drug in December 2018. Besremi® was approved by the EMA as first-line monotherapy to treat adult polycythaemia vera without symptomatic splenomegaly in February 2019.
Polycythaemia vera causes and symptoms
Polycythaemia vera is a type of rare and chronic blood cancer that originates in the bone marrow. The disease causes overproduction of blood cells in the body, which can lead to thickening of the blood, clots, stroke and heart attack.
The disease may cause circulatory disorders such as thrombosis and embolism, as well as other malignancies such as leukaemia.
The underlying molecular mechanism of the disease is not understood and is still under research. The disease is believed to be caused due to impaired Janus Kinase 2 (JAK2) or tet methylcytosine dioxygenase 2 (TET2) gene, which is responsible for the normal production of blood cells in the body.
Men aged 60 years and higher are at a higher risk of the disease. An estimated two out of 100,000 individuals are affected by the disease. Some common symptoms include dizziness, headache, double vision, weight loss, sweating, itching all over the body, dyspnoea and swelling of the joints.
Besremi’s mechanism of action
Besremi® is a long-acting, mono-pegylated proline interferon developed using PharmaEssentia’s novel pegylation technology platform. It has exhibited improved pharmacokinetic properties in clinical studies, including increased tolerability and convenience.
The drug is designed for self-administration subcutaneously once in two weeks. It is taken once monthly in the case of long-term maintenance.
Clinical studies on Besremi
The EC’s approval of Besremi was based on the positive outcomes of a clinical development programme consisting of four clinical studies named PROUD-PV, PEN-PV, PEGINVERA and the on-going CONTINUATION-PV.
PROUD-PV was a Phase III, 12-month, randomised clinical study to evaluate the safety and efficacy of the drug compared to hydroxyurea in PV patients that did not receive prior hydroxyurea treatment.
The primary endpoint of the trial was the Complete Hematologic Response (CHR) rate at 12 months. Ropeginterferon alfa-2b showed better CHR and improved safety and tolerability profile compared to hydroxyurea in the study.
PEN-PV was a Phase III open-label and single-arm study in patients that completed the ropeginterferon alfa-2B arm of the PROUD-PV study. It was performed to evaluate the convenience of self-administration of the drug by patients using a pre-filled pen.
PEGINVERA was an open-label, prospective, multi-centre, Phase I /II dose escalation trial performed to determine the maximum tolerated dose in patients. The subjects were successfully switched from the once every two weeks to four weeks long-term maintenance dosing schedule after a period of two years.
Ropeginterferon alfa-2b demonstrated disease-modifying abilities after four years through the reduction of the mutant JAK2V617F allelic burden to below 10% in the majority of patients.
CONTINUATION-PV is an open-label, multi-centre, Phase IIIb clinical study to determine the long-term efficacy and safety of the drug. The patients that completed the PROUD-PV study were selected to enrol for this study.
Marketing commentary on PharmaEssentia
Based in Taiwan, PharmaEssentia is a biopharmaceutical company focussed on the development of treatments for myeloproliferative neoplasms, hepatitis, and other diseases.
The company granted exclusive license to AOP Pharma for the development and marketing of the ropeginterferon alfa-2b for polycythaemia vera, chronic myeloid leukaemia, and other myeloproliferative neoplasms (MPN) in Europe, Commonwealth of Independent States (CIS), and Middle East markets in 2009.
PharmaEssentia holds the right to the drug in the rest of the major markets including North America, South America, and Asia.