WHA

BESREMI (ropeginterferon alfa-2b-njft)

Self-Administration – subcutaneous (SC) injection

Diagnosis considered for coverage:

For diagnosis of polycythemia vera (PV):

  • Dose does not exceed 500 mcg subcutaneous (SC) injection given every 2 weeks; AND
  • Prescribed by or in consultation with a hematologist or oncologist; AND
  • One of the following:
    • For men: hemoglobin (HGB) greater than 16.5 g/dL, OR hematocrit (HCT) greater than 49%
    • For women: hemoglobin (HGB) greater than 16.0 g/dL, OR hematocrit (HCT) greater than 48%
    • Medical records document red blood cell mass (RCM) is greater than 25% above mean normal predicted; AND
  • Bone marrow biopsy shows hypercellularity (abnormal increase in the number of cells present) for age with prominent erythroid, granulocytic and megakaryocytic production (i.e., trilineage growth) (cells that give rise to RBCs, WBCs, and platelets, respectively) with pleomorphic (different sized), mature megakaryocytes; AND
  • One of the following:
    • Presence of JAK2 mutation associated with PV (e.g., V617F mutation in exon-14; mutation in exon-12)
    • Subnormal serum erythropoietin (EPO) level (normal range: 4-21 mIU/mL); AND
  • Documentation of trial and failure, contraindication or intolerance to two of the following:
    • hydroxyurea
    • peginterferon alfa-2a (Pegasys)
    • ruxolitinib (Jakafi)
Reauthorization Criteria:

For diagnosis of PV:

  • Dose does not exceed 500 mcg SC injection given every 2 weeks; AND
  • Documentation of positive clinical response to therapy (e.g., improvement in hematological response, resolution of splenomegaly, absence of thromboembolic events).
Coverage Duration:
  • Initial: 1 year
  • Reauthorization: 1 year
Authorization is not covered for the following:
  • The use of this drug for indications not listed in this policy does not meet the coverage criteria established by the Western Health Advantage (WHA) Pharmacy and Therapeutics (P&T) Committee.
Additional Information:
  • Polycythemia vera (PV) is one of the myeloproliferative neoplasms (MPNs) that may show a relative erythroid predominance (erythroid elements comprise ≥50% of total bone marrow cells). PV is defined by erythrocytosis (more red blood cells than normal with the exclusion of possible secondary causes), the nearly ubiquitous presence of a JAK2 mutation, and characteristic bone marrow morphology.
  • PV is a rare blood disorder in which there is an increase in all blood cells, particularly red blood cells.
  • Normal ranges for red cell mass (RCM) (mL/kg) rely upon published normal ranges for the interpretation of results. Widely accepted upper limits for the normal range are 36 mL/kg in adult males and 32 mL/kg in adult females. These values are appropriate for persons who are not overweight. However, it is important to note that this range may still lead to excessive misdiagnosis of erythrocytosis or PV in normal, healthy persons.
  • Trilineage growth involves production by myeloid cells in bone marrow of three blood cell lines: red blood cells, certain white blood cells, and platelets
  • According to the World Health Organization (WHO), diagnosis of polycythemia vera requires meeting either all three major criteria or the first two major criteria and one minor criterion. The three major criteria are as follows: 1) Hemoglobin > 16.5 g/dL for men or hemoglobin > 16.0 g/dL for women, or Hematocrit > 49% for men or Hematocrit > 48% for women, or increased red cell mass; 2) Bone marrow biopsy showing hypercellularity for age with trilineage growth (panmyelosis) including prominent erythroid, granulocytic and megakaryocytic proliferation with pleomorphic, mature megakaryocytes (differences in size); 3) Presence of JAK2 or JAK2 exon 12 mutation. The minor criterion is subnormal serum erythropoietin level.
  • JAK2 mutations almost always accompany World Health Organization (WHO)-defined polycythemia vera (PV) (Blood 2016;127:2391); about 97% of these are JAK2 V617F exon 14 mutations while the remainder 3% harbor other JAK2 mutations, of which JAK2 exon 12 mutations are by far the most frequent (Leukemia 2007;21:1960). 
  • Red blood cell mass (RCM) is rarely measured.  RCM can be measured by calculating the total RCM from the dilution factor and a known volume of radiolabeled (chromium-51 [51 Cr]) autologous red blood cells. The RCM is increased if it exceeds 35 mg/kg in males and 31 mg/kg in females.
  • BESREMi (ropeginterferon alfa-2b-njft) is contraindicated in patients with existence of or history of severe neuropsychiatric disorders, particularly severe depression, suicidal ideation or suicide attempt; hepatic impairment (Child-Pugh B or C); history or presence of active serious or untreated autoimmune disease; and immunosuppressed transplant recipients.
  • BESREMi is initiated as 100 mcg by subcutaneous (SC) injection every 2 weeks for patients not receiving hydroxyurea, and 50 mcg by SC injection every 2 weeks for patients transitioning from hydroxyurea. The dose is increased by 50 mcg every 2 weeks (up to a maximum of 500 mcg), until the hematological parameters are stabilized (HCT < 45%, PLT < 400 x 109/L, and WBC < 10 x 109/L).
  • Maintain the two-week dosing interval of BESREMi at which hematological stability is achieved for at least 1 year. After achievement of hematological stability for at least 1 year on a stable dose of BESREMi, the dosing interval may be expanded to every 4 weeks.
Policy Updates:
  • 05/17/2022 – New policy approved by P&T.
References:
  1. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 2016; 127:2391.
  2. BESREMi (ropeginterferon alfa-2b-njft) [Prescribing Information]. Taipei, Taiwan. PharmaEssentia Corporation. November 2021.
  3. Barbui T, Thiele J, Gisslinger H, Kvasnicka HM, Vannucchi AM, Guglielmelli P, Orazi A, Tefferi A. The 2016 WHO classification and diagnostic criteria for myeloproliferative neoplasms: document summary and in-depth discussion. Blood cancer journal. 2018 Feb 9;8(2):1-1.
  4. Gisslinger H, Klade C, Georgiev P, et al for the PROUD-PV Study Group. Ropeginterferon alfa-2b versus standard therapy for polycythemia vera (PROUD-PV and CONTINUATION-PV): a randomized, non-inferiority, phase 3 trial and its extension study. Lancet Haematol. 2020;7:e196-208. doi: 10.1016/S2352-3026(19)30236-4.
  5. Gisslinger H, Klade C, Georgiev P, et al. Polycythemia vera patients respond better to ropeginterferon alfa-2b than HU/BAT irrespective of pretreatment or mutational status; results from 5 years’ treatment in a randomized, controlled setting in the PROUD-PV/CONTINUATION-PV trials. Presented at: American Society of Hematology 63rd Annual Meeting and Exposition; December 10-16, 2021; Atlanta, GA. abstract: 3660.
  6. Pardanani A, Lasho TL, Finke C, Hanson CA, Tefferi A. Prevalence and clinicopathologic correlates of JAK2 exon 12 mutations in JAK2V617F-negative polycythemia vera. Leukemia. 2007 Sep;21(9):1960-3.

 

Last review date: May 17, 2022