Ropeginterferon Alfa-2b Succeeds in Phase 3 Essential Thrombocythemia Trial

Essential thrombocytosis blood smear - ©MdBabul - stock.adobe.com

The SURPASS-ET trial (NCT04285086) of ropeginterferon alfa-2b-njft (P1101; Besremi) in patients with essential thrombocythemia (ET) has met its primary end point, yielding durable clinical response as measured using modified European Leukemia Net (ELN) criteria.¹

In the intent-to-treat (ITT) population, 42.9% (39/91) of patients treated with ropeginterferon alfa-2b had durable responses at 9 and 12 months vs 6.0% (5/83) of patients enrolled in the comparator arm who were treated with anagrelide (Agrylin) (P =.0001).

For the secondary end point, the JAK2 V617F allele burden decreased from 33.7% to 25.3% (-8.4%) in the ropeginterferon alfa-2b group over 12 months, compared with a reduction from 39.7% to 37.3% (-2.4%) in the anagrelide group. These findings indicate that ropeginterferon alfa-2b may provide a more pronounced effect on mitigating the underlying disease pathology relative to anagrelide.

“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 ET, a rare blood cancer that drastically increases the risk of heart attack or stroke,” said Ko-Chung Lin, PhD, founder and chief executive officer of PharmaEssentia, in a press release. “The data highlight the broad potential to apply our innovative monopegylated, long-acting interferon technology as a significant step forward for treating ET, and potentially other myeloproliferative neoplasms, with non-chemotherapy treatments.”

For safety, ropeginterferon alfa-2b did not lead to any treatment-related serious adverse events. Overall, the agent had a manageable safety profile.

Full trial results, including additional pharmacokinetics and biomarker data, are expected to be presented at a later date.

“The results of the SURPASS-ET trial are significant,” said Albert Qin, MD, PhD, chief medical officer, PharmaEssentia, in a press release. “ET 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 ET. 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 ET.”

Behind the SURPASS-ET Study

SURPASS-ET is a phase 3, open-label, multicenter, randomized, active-controlled study evaluating the efficacy, safety, pharmacokinetics, and tolerability of ropeginterferon alfa-2b vs anagrelide as a second-line treatment in ET.²

Male or female patients aged 18 years or older with high-risk ET, diagnosed according to the World Health Organization 2016 criteria, were eligible for enrollment if they had adequate hepatic function.

Primary end points of the study are peripheral blood count remission, improvement or non-progression in disease-related signs, large symptom improvement or maintain non-progression, and absence of hemorrhagic or thrombotic events. Secondary end points include durable response, longitudinal rate, response rates, occurrence of thromboembolic events, time to first peripheral blood count remission response, duration of peripheral blood count remission response, symptomatic improvement assessed by the EuroQOL 5 dimensions 3 level version, symptomatic improvement assessed by the 10-item MPN-SAF TSS, change of CALR, MPL, and JAK-2 allele burden over time, and spleen size assessment.

About Ropeginterferon Alfa-2b

Ropeginterferon alfa-2b is currently an FDA-approved treatment for patients with polycythemia vera.¹ The Company plans to pursue regulatory discussion with the FDA to seek a label expansion to include ET. They anticipate regulatory submission by the end of 2025.

In addition to SURPASS-ET, ropeginterferon alfa-2b is undergoing evaluation in the phase 2b EXCEED-ET (NCT05482971) trial in North America for patients with ET. The single-arm, multicenter trial aims to evaluate the agent’s efficacy, safety, and tolerability in adult patients with ET, with data from the trial expected in the second half of 2025.

“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,” added Lin in the press release.

REFERENCES:

1. PharmaEssentia announces positive topline phase 3 data from SURPASS-ET study evaluating ropeginterferon alfa-2b-njft (P1101) for essential thrombocythemia. News release. January 6, 2025. Accessed January 6, 2025. https://tinyurl.com/yaxrvdtr

2. Ropeginterferon alfa-2b (P1101) vs. anagrelide in essential thrombocythemia patients with hydroxyurea resistance or intolerance (SURPASS ET). ClinicalTrials.gov. Updated November 30, 2024. Accessed January 6, 2025. https://clinicaltrials.gov/study/NCT04285086?tab=table