Accelerated Dosing of Ropeginterferon Alfa-2b May Improve Responses in PV

The dose and titration of ropeginterferon alfa-2b is safe and effective for patients with polycythemia vera. However, additional studies are needed to provide rationale for an amended, higher initial dosage, and rapid titration.

Using an amended dosing schedule consisting of a higher initial dose and faster dose titration of ropeginterferon alfa-2b (Besremi) may lead to an earlier complete hematological response (CHR) in adult patients with polycythemia vera (PV), according to findings published in Frontiers in Oncology.1

According to the publication, multiple studies support the efficacy, safety and tolerability ofropeginterferon alfa-2b at a 250-350-500 mcg titration dosing regimen.

“The accelerated dosing regimen for ropeginterferon would allow more rapid dose optimization with the potential to deliver short time to hematologic response and ultimately molecular response while importantly not adding additional interferon-alfa-related toxicity. This may be particularly relevant in the cases of a myeloproliferative neoplasm patient with poorly controlled counts and high risk of thrombosis," study author John O. Mascarenhas, MD, a professor of Medicine at the Icahn School of Medicine at Mount Sinai and director of the adult leukemia program and leader of clinical investigation within the myeloproliferative disorders program at Mount Sinai, told Targeted OncologyTM.

Ropeginterferon alfa-2b-njft is a monopegylated, long-acting interferon, which was approved by the FDA for patients with PV in November 2021 based on data from the phase 3 PROUD/CONTINUATION-PV clinical trial (NCT01949805; NCT02218047). This study assessed the safety and efficacy of the therapy in 306 patients with PV. A total of 257 patients were randomly assigned treatment, and 171 patients rolled over to the CONTINUATION-PV trial.

In the PROUD-PV group, the ropeginterferon alfa-2b arm met the study end point of CHR with normal spleen size in 21% of the patients vs 28% of the patients given the standard therapy. In the CONTINUATION-PV group, CHR was achieved in 61% of patients administered ropeginterferon alfa-2b-njft, and 80% had a hematological response based solely on laboratory parameters.

In the study, the most common grade adverse events (AEs) which occurred in over 40% of patients included influenza-like illness, arthralgia, fatigue, pruritus, nasopharyngitis, and musculoskeletal pain. Serious AEs seen in more than 4% of patients were urinary tract infection, transient ischemic attack, and depression.

Then using a compassionate use program study, 14 patients with hydroxyurea, and/or anagrelide resistance, or intolerance patients were evaluated in Taiwan.2 These patients had a CHR rate of 73% at 52 weeks. This compared with a CHR rate of 51% observed in a study with a slower titration method. Additionally, there were no new safety signals detected.

In interim data from an ongoing, single-arm, phase study of Chinese patients with PV, 49 patients who are resistant or intolerant to hydroxyurea were evaluated. FIndings showed that treatment with the amended dosing regimen elicited a CHR rate of 52% at week 24 vs 43% at week 52 in the PROUD-PV study. In this trial, 5 patients had treatment-related grade >3 AEs.

Then, data from an investigator-initiated trial conducted in Korea showed that in 45 patients with PV who were hydroxyurea naïve or pre-treated, a higher hematologic and molecular response was seen at 6 months. A total of 4.4% of patients required dose reductions and regarding safety, most AEs were deemed grade 1 or 2 with no treatment-related serious AEs reported.

Overall, ropeginterferon alfa-2b was proven to be generally well-tolerated across multiple studies. With the amended dosing schedule in PV, there were no thromboembolic complications reported. As a result, researchers conclude that this accelerated dosing regimen may lead to a decreased risk of thrombosis and hemorrhage that correlates with an under-dosing during dose titrations.

To further evaluate this regimen of ropeginterferon alfa-2b, there are several planned studies in essential thrombocytopenia including the SURPASS (NCT04285086) and EXCEED trials (NCT05482971), and the ECLIPSE trial (NCT05481151) in PV. A phase 3 clinical trial in primary myelofibrosis is also anticipated.

“As more clinicians gain familiarity with [ropeginterferon alfa-2b], we want to support treatment goals by ensuring patients can effectively achieve and maintain their target clinical and molecular responses, as this may help reduce the risk of disease progression over time,” said Raymond Urbanski, MD, PhD, senior vice president and United States head of clinical development and medical affairs, in the press release. “This latest research will help support more informed dialogue among physicians regarding their patients with PV.”

Clinical review of ropeginterferon alfa-2b suggests amended dosing schedule may support improved clinical outcomes in polycythemia vera. News release. PharmaEssentia USA Corporation. February 2, 2023. Accessed February 6, 2023.
Qin A, Urbanski RW, Yu L, et al. An alternative dosing strategy for ropeginterferon alfa-2b may help improve outcomes in myeloproliferative neoplasms: An overview of previous and ongoing studies with perspectives on the future. Front Oncol. 2023;13. doi:10.3389/fonc.2023.1109866
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