Evaluating ropeginterferon alfa-2b for the treatment of adults with polycythemia vera

ABSTRACT

Introduction

Interferons (IFNs) have been used for decades to treat polycythemia vera (PV). Single-arm clinical trials assessing IFN in PV patients demonstrated high hematological and molecular response rates, indicating potential disease-modifying activity of IFN. However, discontinuation rates of IFNs have been rather high due to frequent treatment-related side-effects.

Areas covered

Ropeginterferon alfa-2b (ROPEG) is a monopegylated IFN consisting of a single isoform, which differentiates it from previous IFNs with respect to tolerability and dosing frequency. ROPEG has improved pharmacokinetic and pharmacodynamic properties, which allow extended dosing every 2 weeks and monthly administration during maintenance phase. This review covers ROPEG’s pharmacokinetic and pharmacodynamic properties, presents results of randomized clinical trials (RCT) that evaluated ROPEG in the treatment of PV patients, and discusses contemporary findings regarding the potential disease-modifying activity of ROPEG.

Expert opinion

RCT have demonstrated high rates of hematological and molecular responses in PV patients treated with ROPEG, irrespective of thrombotic risk. Drug discontinuation rates were generally low. However, even though RCT captured the most important surrogate endpoints of thrombotic risk and disease progression in PV, they were not statistically powered to fully determine whether therapeutic intervention with ROPEG indeed has a direct positive effect on these important clinical outcomes.

KEYWORDS:

• Ropeginterferon alpha-2b
• polycythemia vera
• myeloproliferative neoplasms
• thrombosis
• molecular response

Article highlights

• Ropeginterferon alfa-2b (ROPEG) is a monopegylated interferon (IFN) with improved tolerability which enables less frequent dosing intervals.

• The results from the PROUD/CONTINUATION-PV phase 3 randomized clinical trial have shown durable hematological and molecular response rates during long-term treatment with ROPEG in treatment-naïve and inadequately controlled low- and high-risk polycythemia vera (PV) patients at 5 years of follow-up (and beyond).

• The Low-PV clinical trial demonstrated that the addition of ROPEG to phlebotomy in low-risk PV patients is superior to phlebotomy alone in maintaining the hematocrit <45% at 12 months.

• In clinical trials, ROPEG was well tolerated, and discontinuation rates were considered low (8–10%).

• High hematological and molecular response rates during long-term treatment with ROPEG may indicate a potential disease-modifying activity of ROPEG in PV patients. Although thrombotic events and disease progression rates were low in the clinical trials, the studies were not statistically powered to test whether ROPEG indeed delays disease transformation or mitigates thrombotic risk in PV patients.

• Future studies are needed to determine whether longer treatment with ROPEG or combination therapies (i.e. with HU or ruxolitinib) can elicit more sustained responses and treatment-free remissions in PV patients.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Scientific accuracy review

PharmaEssentia provided a scientific accuracy review at the request of the journal editor.

Additional information

Funding

This paper was not funded.