Expanding indication for 'Besremi' to treat ET in KOR

The U.S. FDA decision date is scheduled for the end of this month...The Phase 3 trial also included patients in South Korea

Confirmed improvement in PFS rate compared to Anagrelide

PharmaEssentia's 'Besremi'

The treatment area of Besremi (ropeginterferon alfa-2b), a treatment for polycythemia vera (PV), is expanding to include essential thrombocythemia (ET).

​While an approval decision is expected in the United States by the end of this month, PharmaEssentia Korea plans to submit a domestic marketing authorization application that can also be submitted for the US-approved indication. Because South Korean patients participated in the global Phase 3 clinical trial, the domestic indication expansion is also projected to accelerate.

​According to industry sources on the 22nd, the U.S. Food and Drug Administration (FDA) is reviewing a supplemental Biologics License Application (sBLA) to add the ET indication for Besremi. The FDA-designated Prescription Drug User Fee Act (PDUFA) decision date is August 30, local time.

​An official from PharmaEssentia Korea said, "The application submitted to the FDA is for patients with essential thrombocythemia requiring cytoreductive therapy," adding, "The company plans to file with the Ministry of Food and Drug Safety (MFDS) in accordance with the FDA-approved indication."

​Besremi is a long-acting interferon formulation currently used in South Korea to treat polycythemia vera. In October 2021, it was approved for the treatment of polycythemia vera without symptomatic splenomegaly in low-risk patients requiring cytoreductive therapy and in high-risk patients, subsequently entering National Health Insurance reimbursement in September of last year.

If ET indication is added, Besremi will secure its second approved indication to treat myeloproliferative neoplasm (MPN) disease.

​Essential thrombocythemia is a chronic myeloproliferative neoplasm characterized by the overproduction of platelets in the bone marrow. As platelet counts rise, the risk of thrombosis or hemorrhage can increase. In some cases, patients progress to myelofibrosis or acute leukemia.

​In patients at high risk of thrombosis, cytoreductive therapy is utilized to lower platelet counts. Hydroxyurea (HU) is predominantly used, and when patients do not respond sufficiently or cannot sustain treatment because of adverse reactions, alternatives such as Anagrelide or interferon may be considered. According to PharmaEssentia, no new therapeutic agent has been approved for ET in the United States since Anagrelide in 1997.

​Superiority over Anagrelide in patients who are HU-refractory or intolerant

​The primary clinical basis for the FDA regulatory submission is the global Phase 3 SURPASS-ET trial.

The ​SURPASS-ET trial is a randomized clinical trial directly comparing the efficacy and safety of Besremi and Anagrelide in 174 patients with ET who are refractory or intolerant to hydroxyurea.

​In South Korea, seven institutions participated in the trial, including Seoul National University Hospital, Severance Hospital, Soonchunhyang University Seoul Hospital, Samsung Medical Center, Seoul St. Mary's Hospital, Korea University Guro Hospital, and Daegu Catholic University Medical Center.

​The primary endpoint was the proportion of patients maintaining a response according to modified European LeukemiaNet (ELN) criteria at 9 and 12 months.

​In the study, the sustained response rate in the Besremi treatment group was 42.9%, significantly higher than the 6.0% observed in the anagrelide group.

​Specifically, 56.0% of patients achieved platelet control at or below 400×10⁹/L and leukocyte control below 9.5×10⁹/L in the Besremi group, compared with 6.0% in the anagrelide group.

​The proportion of patients with improvement or stabilization in disease-related symptoms was 71.4% in the Besremi group, higher than 33.7% in the anagrelide group. The rate of splenomegaly improvement or stabilization was 87.9% in the Besremi group versus 54.2% in the anagrelide group.

​Divergence was also observed in thrombosis-related outcomes. Major thrombotic events associated with ET occurred in 1 patient (1.1%) in the Besremi group, whereas 7 patients (8.8%) reported events in the anagrelide group.

​The JAK2 V617F allele burden, which reflects changes in disease-driving clones, also declined after Besremi administration. In the Besremi group, the mean allele burden decreased from 33.7% at baseline to 25.3% at 12 months, whereas the anagrelide group showed a smaller change, from 39.7% to 37.3%.

​In terms of safety, the rate of treatment discontinuation due to adverse events was 5.5% in the Besremi cohort compared to 18.8% in the anagrelide cohort, while treatment-related serious adverse events were recorded at 2.2% and 10.0%, respectively.

​Expanding clinical evidence to treatment-naïve patients

​Following the SURPASS-ET trial, PharmaEssentia is evaluating Besremi's potential across a broader range of ET patients.

​The Phase 2b EXCEED-ET trial conducted in North America enrolled both treatment-naïve and previously treated patients. In this study, the durable objective response rate with Besremi was 60.2%.

Overall analysis results released this year also confirmed hematologic and molecular responses regardless of prior lines of therapy, race, or specific driver mutation subtypes such as JAK2, CALR, and MPL.

​Long-term follow-up data also suggested disease control benefits in patients initiating Besremi at an earlier stage. In a 2-year analysis of the SURPASS-ET trial, the estimated 24-month progression-free survival (PFS) rate for patients receiving frontline Besremi reached 76.9%, exceeding the 43.1% recorded in patients who switched to Besremi following anagrelide treatment.

​Based on these clinical trial outcomes, PharmaEssentia plans to propose a therapeutic strategy in ET that extends beyond basic platelet count control to reducing disease-associated clones.