Ropeginterferon Alfa-2b Shows Superior Efficacy Over Anagrelide in Phase 3 Essential Thrombocythemia Trial
核心洞察
Ropeginterferon alfa-2b demonstrated statistically superior durable responses compared to anagrelide in patients with hydroxyurea-intolerant or -refractory essential thrombocythemia (搜索), achieving 43% response rates versus 6% at months 9 and 12.
The phase 3 SURPASS-ET trial results, published in The Lancet Haematology, showed the therapy also reduced JAK2 V617F (搜索) allele burden, indicating potential disease-modifying activity in myeloproliferative neoplasms (搜索).
PharmaEssentia (搜索) plans to submit a supplemental biologics license application to the FDA before year-end 2025 to expand the drug's current polycythemia vera (搜索) indication to include essential thrombocythemia (搜索).
Ropeginterferon alfa-2b-njft (Besremi) has demonstrated superior efficacy and safety compared to anagrelide in patients with hydroxyurea-intolerant or -refractory essential thrombocythemia (搜索) (ET) with leukocytosis, according to results from the pivotal phase 3 SURPASS-ET trial published in The Lancet Haematology.
The randomized, open-label, multicenter study met its primary endpoint, showing that ropeginterferon alfa-2b achieved durable clinical responses per modified European Leukemia Net (ELN) criteria in 43% of patients at months 9 and 12, compared to only 6% of patients receiving anagrelide. This 36.5% difference was statistically significant (95% CI, 25.4%-47.7%; P =.0001).
Trial Design and Patient Population
The SURPASS-ET trial enrolled 174 patients who were randomly assigned to receive either 250 to 500 mcg of ropeginterferon alfa-2b by subcutaneous injection once every 2 weeks (n = 91) or 0.5 mg of anagrelide daily (n = 83). The study's primary endpoints included peripheral blood count remission, improvement or nonprogression in disease-related signs, symptom improvement or maintenance of nonprogression, and absence of hemorrhagic or thrombotic events.
Safety Profile and Additional Benefits
Ropeginterferon alfa-2b demonstrated a tolerable safety profile that was largely favorable relative to anagrelide. Patients in the ropeginterferon alfa-2b group experienced a lower rate of grade 3 or worse treatment-emergent adverse events compared with those in the anagrelide group (23% vs 34%). No treatment-related deaths occurred in either group.
Beyond the primary endpoint, the therapy showed more robust hematologic responses, greater symptom improvement, improved control of splenomegaly, fewer thromboembolic events, and deeper molecular responses across key patient subgroups. Notably, treatment with ropeginterferon alfa-2b resulted in significant reductions in JAK2 V617F (搜索) allele burden, an important indicator of potential disease-modifying activity in myeloproliferative neoplasms (搜索).
Clinical Significance and Expert Commentary
"The SURPASS-ET data are impressive and demonstrate not only durable clinical and symptomatic benefits with ropeginterferon alfa-2b, but also reductions in JAK2 V617F (搜索) allele burden—an important marker associated with potential disease modification," said Ruben Mesa, MD, lead author of the publication and principal investigator of the SURPASS-ET trial. "ET remains a challenging chronic disease, and patients who are resistant or intolerant to hydroxyurea have had few alternatives for sustained disease control. After nearly three decades without new therapeutic options, these findings represent a promising step forward for patients and clinicians."
Regulatory Path Forward
With these positive results, PharmaEssentia (搜索) has begun pursuing label expansion to include ET with submission of a supplemental biologics license application to the FDA, anticipated before year-end 2025. The company expects potential commercialization in this new indication in 2026, pending FDA approval.
"Ropeginterferon alfa-2b-njft has already reshaped the treatment landscape for polycythemia vera (搜索), and the findings from this study further reinforce its potential to benefit patients across the MPN spectrum," said Ko-Chung Lin, PhD, CEO of PharmaEssentia (搜索). "We look forward to advancing our regulatory efforts to bring this therapy to individuals living with ET."
Current Therapeutic Context
Ropeginterferon alfa-2b is a next-generation interferon-based therapy currently approved by the FDA in 2021 for the treatment of adults with polycythemia vera (搜索) and is a recommended treatment for myeloproliferative neoplasms (搜索) under National Comprehensive Cancer Network guidelines. The drug has not yet been approved by the FDA for ET, representing a significant unmet medical need as there have been no new treatments approved in the United States for ET since anagrelide in 1997.
Essential thrombocythemia (搜索) is a rare blood disorder and type of myeloproliferative neoplasm characterized by the bone marrow overproducing platelets. Patients with ET are at increased risk of blood clots, abnormal bleeding, and enlarged spleens, often caused by genetic mutations such as JAK2.