Second-Line Ropeginterferon Alfa-2b Boosts Responses in Essential Thrombocythemia

Second-line ropeginterferon alfa-2b-njft (Besremi) increased responses compared with anagrelide (Agrylin) in patients with essential thrombocythemia who were resistant or intolerant to hydroxyurea, meeting the primary end point of the phase 3 SURPASS ET trial (NCT04285086).1

Findings showed that, in the intention-to-treat population, responses were observed at 9 and 12 months in 42.9% of patients administered ropeginterferon alfa-2b (n = 91) compared with 6.0% for those given anagrelide (n = 83; P = .0001). Responses were evaluated per modified European Leukemia Net criteria.

Data also showed that JAK2 V617F allelic burden decreased from 33.7% at baseline to 25.3% at 12 months in the ropeginterferon alfa-2b group vs a decrease from 39.7% to 37.3% in the anagrelide group.

Safety data showed ropeginterferon alfa-2b was manageable, and no patients in the experimental arm experienced serious treatment-related adverse effects.

“We are extremely proud of the SURPASS ET phase 3 study outcome, which shows the potential of [ropeginterferon alfa-2b] as an important new treatment option for patients with essential thrombocythemia, a rare blood cancer that drastically increases the risk of heart attack or stroke,” Ko-Chung Lin, PhD, founder and chief executive officer of PharmaEssentia, stated in a news release. “The data highlight the broad potential to apply our innovative monopegylated, long-acting interferon technology as a significant step forward for treating essential thrombocythemia, and potentially other myeloproliferative neoplasms, with non-chemotherapy treatments. We plan to leverage these data to expand the existing [ropeginterferon alfa-2b] product label and further expand the reach of [ropeginterferon alfa-2b] to address this growing global unmet medical need.”

In November 2021, the FDA approved ropeginterferon alfa-2b for the treatment of patients with polycythemia vera.2

SURPASS ET was an open-label, multicenter, randomized, active-control study that enrolled patients at least 18 years of age with high-risk essential thrombocythemia per WHO 2026 criteria—defined as either being older than 60 years of age and JAK2 V617 positive at screening; or having a history of disease-related thrombosis or hemorrhage.3 Prior treatment with hydroxyurea was required, and patients needed to have resistance or intolerance to the agent. Adequate hematologic, hepatic, and renal function was required.

Key exclusion criteria consisted of known risk factors for QT-prolongation; comorbidities with severe or serious conditions that could affect protocol compliance, including significant cardiac disease and pulmonary hypertension; a history of major organ transplantation; and the use of any investigational drug less than 4 prior to the first study dose.

Patients were randomly assigned to receive ropeginterferon alfa-2b at 250 µg to 500 µg once every 2 weeks; or anagrelide administered per label and physician judgement.

The study’s end points were peripheral blood count remission; improvement or non-progression in disease-related signs; large symptoms improvement or maintaining non-progression; and the absence of hemorrhagic or thrombotic events. Each end point was measured at month 9 and month 12.

“The results of the SURPASS-ET trial are significant,” Albert Qin, MD, PhD, chief medical officer of PharmaEssentia, stated in a news release.1 “Essential thrombocythemia is a challenging condition associated with symptoms and risks of thrombosis and disease progression. These encouraging results highlight the potential of [ropeginterferon alfa-2b] to provide an effective and tolerable new treatment option that we believe could provide a substantial clinical benefit for patients with essential thrombocythemia. We plan to submit these results to the FDA and other regulatory agencies as soon as possible in hopes of providing this potential new treatment option to patients with essential thrombocythemia.”

References

1. PharmaEssentia announces positive topline phase 3 data from SURPASS-ET study evaluating ropeginterferon alfa-2b-njft (P1101) for essential thrombocythemia. News release. PharmaEssentia. January 6, 2025. Accessed January 6, 2025. https://us.pharmaessentia.com/wp-content/uploads/2025/01/PharmaEssentia-SURPASS-ET-Data-Readout.pdf
2. FDA Approves Treatment for Rare Blood Disease. FDA. November 12, 2021. Accessed January 6, 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-treatment-rare-blood-disease
3. Ropeginterferon alfa-2b (P1101) vs. anagrelide in essential thrombocythemia patients with hydroxyurea resistance or intolerance (SURPASS ET). ClinicalTrials.gov. Updated November 30, 2023. Accessed January 6, 2025. https://clinicaltrials.gov/study/NCT04285086