Coverage Policy Manual
Policy #: 2008025
Category: Pharmacy
Initiated: September 2008
Last Review: May 2018
  Stem Cell Growth Factor, Romiplostim (Nplate)

Description: Romiplostim is a thrombopoiesis stimulating protein (peptibody) that binds to and activates the human thrombopoietin receptor despite having no sequence homology with human thrombopoietin.  Romiplostim has been shown to produce a dose dependent increase in platelet counts in healthy volunteers and improve platelet counts during short term use in patients with chronic immune thrombocytopenic purpura (ITP).

The FDA has expressed concerns over the limited clinical data available on romiplostim.  This included safety concerns which included reticulin fibrosis in the bone marrow, which is associated with benign and malignant conditions, blood clots, immunogenicity and thrombocytopenia recurrence after therapy is stopped.  The drug may also increase the proportion of blast cells in the peripheral blood of some patients with myelodysplastic syndromes.

Policy/
Coverage:
Effective May 2013
Treatment with romiplostim (Nplate) meets primary coverage criteria for effectiveness and is covered to decrease the risk of bleeding for patients with chronic immune (idiopathic) thrombocytopenic purpura (ITP) when:
 
    • The initial platelet count is less than 50,000/ µL, and
    • There is documented insufficient response to other treatment regimens that include corticosteroids, immunoglobulins, and/or splenectomy.   
 
Treatment with romiplostim (Nplate), in such patients, meets primary coverage criteria until the platelet count reaches 300,000/ µL.
 
Note- romiplostim (Nplate) should be discontinued if the platelet count does not increase after 4 weeks at the maximum dose (10mcg/kg).
 
The use of romiplostim (Nplate)   for any indication not listed above does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
 
For members with contracts without primary coverage criteria, the use of romiplostim (Nplate) for any indication not listed above is considered investigational.  Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective prior to May 2013
Romiplostim (Nplate) meets primary coverage criteria for effectiveness and is covered to decrease the risk of bleeding for patients with chronic immune (idiopathic) thrombocytopenic purpura (ITP) when
    • The platelet count is less than 50,000/ µL, and
    • There is documented insufficient response to other treatment regimens that include corticosteroids, immunoglobulins, and/or splenectomy.  
 
There is no coverage for romiplostim when the platelet count is 300,000/µL or higher.
 
The use of romiplostim for any indication not listed as covered does not meet Primary Coverage Criteria of the applicable benefit certificate or health plan.  The Criteria require, among other things, that there be scientific evidence of effectiveness, as defined in the Criteria.  The Criteria exclude coverage of interventions if there is a lack of scientific evidence regarding the intervention, or if the available scientific evidence is in conflict or the subject of continuing debate.
 
For member benefit contracts or Plans with explicit exclusion language for experimental or investigational services, the use of romiplostim for any indication not listed as covered is not covered because it is considered experimental or investigational as defined in the applicable benefit contract or health plan, which excludes coverage of experimental or investigational treatment or services.

Rationale:
The study to support FDA approval of NplateTM  by Kuter DJ et al were two parallel prospective, multicenter, international phase III studies that were randomized, placebo-controlled double blind trails lasting 6 months.  The studies investigated Romiplostim vs. placebo in adults with chronic ITP  which had either been splenectomized (N=63) of non-splenectomized (N=62) and had a mean of three platelet counts of 30,000/µL or less received subcutaneous injections of Romiplostim for 24 weeks.   Doses were adjusted during the study to maintain a platelet count of 50,000/µL  to 200,000/µL.  Those assigned to placebo (N=21 for both groups) received adjusted doses of placebo through the study.
 
Objectives of the study were to assess the efficacy of romiplostim as measured by an increase platelet count of 50,000/µL during 6 of the last 8 weeks of the study and safety profile.
 
Results showed the splenectomized group had a durable platelet response in 16 of 42 in the Romiplostim group versus none in the placebo group (p=0.0013).  In the non splenectomized group, 25 of the 41 that received romiplostim has a durable platelet response versus 3 of 21 in the placebo group (p<0.0001).
 
The study was funded by Amgen, Inc which in collaboration with the investigators, designed the study, did the statistical analysis, and interpreted the data which Amgen holds.
 
The product labeling, FDA approved in AUG 2008, indicates this drug should not be used in an attempt to normalize platelet counts.
 
2012 Update
A search of the MEDLINE database conducted through August 2012 did not reveal any new literature that would prompt a change in the coverage statement.
 
2014 Update
A literature search conducted through April 2014 did not reveal any new information that would prompt a change in the coverage statement.
 
2015 Update
A literature search conducted using the MEDLINE database through April 2015 did not reveal any new information that would prompt a change in the coverage statement.
   
2016 Update
A literature search conducted through April 2016 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
In a phase 3 double-blind study, Tarantino and colleagues aimed to assess whether romiplostim is safe and effective in children with immune thrombocytopenia of more than 6 months' duration (Tarantino, 2016). Eligible participants were children with immune thrombocytopenia aged 1 year to 17 years and mean platelet counts 30 × 109/L or less (mean of two measurements during the screening period) with no single count greater than 35 × 109/L, and were recruited from 27 sites in the USA, Canada, and Australia. Participants were randomly assigned (2:1) through the interactive voice response system to receive weekly romiplostim or placebo for 24 weeks stratified by age (1 year to <6 years, 6 years to <12 years, 12 years to <18 years), adjusting the dose weekly from 1 μg/kg to 10 μg/kg to target platelet counts of 50-200 × 109/L. Patients and investigators were blinded to the treatment assignment. The primary analysis included all randomised patients and the safety analysis included all randomised patients who received at least one dose of investigational product. The primary endpoint, durable platelet response, was defined as achievement of weekly platelet responses (platelet counts ≥50 × 109/L without rescue drug use in the preceding 4 weeks) in 6 or more of the final 8 weeks (weeks 18-25). This study is registered with ClinicalTrials.gov, (NCT 01444417). Between Jan 24, 2012, and Sept 3, 2014, 62 patients were randomly assigned; 42 to romiplostim and 20 to placebo. Durable platelet response was seen in 22 (52%) patients in the romiplostim group and two (10%) in the placebo group (p=0·002, odds ratio 9·1 [95% CI 1·9-43·2]). Durable platelet response rates with romiplostim by age were 38% (3/8) for 1 year to younger than 6 years, 56% (10/18) for 6 years to younger than 12 years, and 56% (9/16) for 12 years to younger than 18 years. One (5%) of 19 patients in the placebo group had serious adverse events compared with 10 (24%) of 42 patients in the romiplostim group. Of these serious adverse events, headache and thrombocytosis, in one (2%) of 42 patients in the romiplostim group, were considered treatment related. No patients withdrew due to adverse events. In children with chronic immune thrombocytopenia, romiplostim induced a high rate of platelet response with no new safety signals. Ongoing romiplostim studies will provide further information as to long-term efficacy, safety, and remission in children with immune thrombocytopenia.
 
In a phase 3, randomized, double-blind, placebo-controlled study Mathias and colleagues sought to examine the effect of romiplostim on HRQoL and parental burden in children with primary ITP (Mathias, 2016). Children aged <18 years with ITP ≥6 months were randomly assigned to receive romiplostim or placebo for 24 weeks. The Kids' ITP Tool (KIT) was used to measure HRQoL and was administered to patients and/or their parents at baseline and weeks 8, 16, and 25. Mean KIT scores at each assessment and mean changes in KIT scores from baseline were calculated overall by treatment group and platelet response status. Psychometric properties of the KIT were evaluated and the minimally important difference (MID) was estimated for different KIT versions. Sixty-two patients (42 romiplostim and 20 placebo) were enrolled. Changes in KIT scores by treatment group showed numerically greater and more often statistically significant improvements from baseline to each assessment for children receiving romiplostim versus placebo. Mixed-effects analysis demonstrated statistically significantly greater reduction in parental burden from baseline in the romiplostim group versus placebo. Ranges for the MID were estimated as 9-13 points for the Child Self-Report version and 11-13 points for the Parent Impact version. The treatment with romiplostim may be associated with improved HRQoL in children with primary ITP and reduced burden to their parents.
 
2017 Update
A literature search conducted through April 2017 did not reveal any new information that would prompt a change in the coverage statement.
 
2018 Update
Annual policy review completed with a literature search using the MEDLINE database through April 2018. No new literature was identified that would prompt a change in the coverage statement.

CPT/HCPCS:
J2796Injection, romiplostim, 10 mcg
J3490Unclassified drugs

References: Bussel JB, Kuter DJ, et al.(2006) AMG531, a thrombopoiesis-stimulating protein for chronic ITP. New Eng J Med. 2006; 335:1672-81.

Kuter DJ, Bussel JB, et al.(2008) Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet. 2008; 372:395-403.

Mathias SD, Li X, Eisen M et al.(2016) A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Determine the Effect of Romiplostim on Health-Related Quality of Life in Children with Primary Immune Thrombocytopenia and Associated Burden in Their Parents. Pediatr Blood Cancer. 2016 Apr 1

Tarantino MD, Bussel JB, Blanchette VS et al.(2016) Romiplostim in children with immune thrombocytopenia: a phase 3, randomised, double-blind, placebo-controlled study. Lancet. 2016 Apr 18. pii: S0140-6736(16)00279-8


Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
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