Ropeginterferon alfa-2b, a novel mono-pegylated interferon, is showing promise in the treatment of myeloproliferative neoplasms (MPNs), particularly polycythemia vera (PV). While the drug is already approved for PV, recent studies suggest that an alternative, more aggressive dosing strategy could lead to improved patient outcomes. This approach involves a higher initial dose and rapid titration, potentially optimizing both tolerability and efficacy.
Current Clinical Experience with Ropeginterferon Alfa-2b in PV
The PEGINVERA, PROUD-PV, and CONTINUATION-PV trials established the safety and efficacy of ropeginterferon alfa-2b in PV. The approved dosing regimen starts at 100 mcg (or 50 mcg for patients on hydroxyurea) and increases by 50 mcg every two weeks, up to a maximum of 500 mcg, until hematological parameters are stabilized. However, emerging data suggest that a more rapid titration schedule, starting at a higher dose, may offer advantages.
Investigational Studies: A Shift Towards Rapid Titration
Several ongoing international studies are exploring the 250-350-500 mcg dosing regimen. Interim results from a Phase 2 study in China, involving PV patients resistant or intolerant to hydroxyurea, showed a 52% complete hematologic response (CHR) rate at Week 24. This is comparable to the 43% CHR rate at Week 52 observed in the PROUD-PV study, suggesting a faster response with the more aggressive dosing.
Similarly, a study in South Korea evaluating the 250-350-500 mcg regimen in PV patients (treatment-naïve or previously treated) demonstrated good tolerability and promising hematological and molecular responses. The JAK2V617F variant allele frequency (VAF) decreased rapidly, from 59.7% at baseline to 42.4% at Month 3 and 37.1% at Month 6.
The ECLIPSE-PV study (Phase 3b) is further assessing this higher-dose regimen in North American PV patients, with the hypothesis that response rates similar to those in PROUD/CONTINUATION-PV can be achieved more quickly.
Potential Benefits of a Higher Starting Dose
One key consideration is the risk of thromboembolic events, which is highest around the time of PV diagnosis. The standard, slower titration regimen may delay hematologic response, potentially leaving patients vulnerable. A higher starting dose and faster titration could mitigate this risk by inducing more rapid hematologic remission and molecular response, including a reduction in JAK2V617F VAF.
Expanding the Scope: Ropeginterferon Alfa-2b in Other MPNs
While currently approved only for PV, ropeginterferon alfa-2b is also being investigated in essential thrombocythemia (ET) and myelofibrosis (MF). The SURPASS-ET (Phase 3) and EXCEED-ET trials are evaluating the 250-350-500 mcg dosing scheme in ET patients. A Phase 2 study in pre-fibrotic PMF showed clinical improvements with ropeginterferon alfa-2b, and an ongoing investigator-initiated trial is assessing the higher-dose regimen in early MF.
Compassionate Use Program Data
Data from a compassionate use program in Taiwan, involving MPN patients resistant or intolerant to standard therapies, further support the potential of the 250-350-500 mcg regimen. In PV patients, the median time to CHR was 27 weeks, compared to 52 weeks in a study using the slower titration regimen. Overall, ropeginterferon alfa-2b at this dosing regimen appears to offer notable and rapidly occurring clinical activity with manageable tolerability in MPNs.
Conclusion
Emerging data suggest that a higher initial dose and faster titration of ropeginterferon alfa-2b may lead to earlier and more robust responses in PV and other MPNs. Ongoing clinical trials are crucial to further define the optimal dosing strategy and its impact on critical efficacy and tolerability outcomes.
