NCCN Lists Ropeginterferon Alfa-2B As Preferred First-Line Cytoreductive Therapy for Polycythemia Vera

Rami Komrokji, MD

The National Comprehensive Cancer Network (NCCN) has recommended ropeginterferon alfa-2b-njft (Besremi) as a first-line cytoreductive therapy for patients with polycythemia vera (PV) in the NCCN Clinical Practice Guidelines in Oncology for Myeloproliferative Neoplasms (MPNs).¹

In version 1.2024 of the NCCN guidelines for MPNs, updated on December 21, 2023, ropeginterferon alfa-2b is listed as the preferred first-line method for cytoreductive therapy for adult patients with low-risk, symptomatic PV.^1,2 Ropeginterferon-alfa-2b is the only preferred treatment option for patients with both low-risk and high-risk PV regardless of treatment history. In the guidelines, ropeginterferon alfa-2b-njft is also listed as a category 2A therapy, indicating a unanimous NCCN consensus that this agent is appropriate for its indicated uses.

“The recent update to the NCCN Guidelines reflects the ongoing shift in PV care toward earlier intervention, focusing on long-term patient health,” Rami Komrokji, MD, vice chair of the Malignant Hematology Department and head of the Leukemia and Myelodysplastic Syndromes Section at Moffitt Cancer Center in Tampa, Florida, stated in a news release.¹

Previously, ropeginterferon alfa-2b received FDA orphan drug designation for the treatment of adult patients with PV. In 2021, the FDA approved the agent for this indication based on safety findings from the phase 1/2 PEGINVERA clinical study program (NCT01193699) and phase 3 PROUD-PV (NCT01949805) and CONTINUATION-PV (NCT02218047) trials, as well as efficacy findings from PEGINVERA.³

Following 7.5 years of treatment with ropeginterferon alfa-2b in the PEGINVERA study, 61% of patients with PV achieved a complete hematological response and a normal spleen size. Furthermore, 80% of patients experienced a hematological response. Pooled safety data in patients who received ropeginterferon alfa-2b showed that the most common adverse effects (AEs) were arthralgia, influenza-like illness, fatigue, nasopharyngitis, musculoskeletal pain, and pruritus. Serious AEs included transient ischemic attack, depression, and urinary tract infection.

“This is another important milestone for [ropeginterferon alfa-2b] as a preferred, FDA-approved option for both symptomatic low- and high-risk patients [with PV],” Albert Qin, MD, PhD, chief medical officer at PharmaEssentia Corporation, added in the news release.¹ “We are encouraged by the increasing dialogue across academic and community healthcare practitioners rethinking treatment approaches given the potential of [ropeginterferon alfa-2b] for this MPN.”

Two dosing regimens of ropeginterferon alfa-2b are also under investigation in adult patients with PV in the randomized, open-label, parallel group, multicenter, phase 3b ECLIPSE PV trial (NCT05481151).4 One arm will consist of patients receiving the agent on the approved dosing schedule with a starting dose of 100 mcg at day 0 that will increase by 50 mcg every 2 weeks to a maximum dose of 500 mcg. The other arm will be treated with the agent on an amended dosing schedule with a starting dose of 250 mcg on day 0 that will increase to 350 mcg at further increase to a maximum dose of 500 mcg at week 4.⁴

This trial plans to enroll approximately 100 patients from the United States and Canada. The primary end point is complete hematologic response at week 24, defined as hematocrit levels below 45% without phlebotomy in the previous 12 weeks, as well as white blood cell counts less than or equal to 10 x 10⁹/L and platelet counts less than or equal to 400 x 10⁹/L. Key secondary end points include time to complete hematologic response; proportion of patients in complete hematologic response at weeks 8, 12, 16, 20, 24, 36, and 48; time to freedom from phlebotomies; and time to maintenance dose. Dosing for ECLIPSE PV has begun, and topline data are expected in 2024.⁵

References

1. PharmEssentia’s Besremi (ropeginterferon alfa-2b-njft) now recommended as a preferred first-line cytoreductive therapy for polycythemia vera in updated NCCN Clinical Practice Guidelines in Oncology. News Release. PharmEssentia. February 27, 2024. Accessed February 28, 2024. https://us.pharmaessentia.com/wp-content/uploads/2024/02/NCCN-Guidelines-2024-Press-Release.pdf
2. NCCN. Clinical Practice Guidelines in Oncology. Myeloproliferative neoplasms, version 1.2024. Accessed February 28, 2024. https://www.nccn.org/professionals/physician_gls/pdf/mpn.pdf
3. US FDA approves Besremi (ropeginterferon alfa-2b-njft) as the only interferon for adults with polycythemia vera. News release. PharmaEssentia Corporation. November 12, 2021. Accessed February 28, 2024. https://www.businesswire.com/news/home/20211112005909/en/U.S.-FDA-Approves-BESREMi%C2%AE-ropeginterferon-alfa-2b-njft-as-the-Only-Interferon-for-Adults-With-Polycythemia-Vera
4. Mascarenhas J, Tashi T, El Chaer F, et al. A phase 3b, randomized, open-label, parallel group, multicenter study to assess efficacy, safety, and tolerability of two dosing regimens of ropeginterferon alfa-2b-njft (P1101) in adult patients with polycythemia vera. Blood. 2023;142(suppl 1):6444. doi:10.1182/blood-2023-189912
5. PharmaEssentia initiates phase 3b trial of ropeginterferon alfa-2b-njft investigating new dosing regimen for patients with polycythemia vera (PV). News release. PharmaEssentia. May 3, 2023. Accessed February 28, 2024. https://us.pharmaessentia.com/wp-content/uploads/2023/05/ECLIPSE-PV_Initiation_Press_Release_May-3-2023-1.pdf