Coverage Policy Manual
Policy #: 2008025
Category: Pharmacy
Initiated: September 2008
Last Review: May 2024
  Stem Cell Growth Factor, Romiplostim (e.g., 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 individuals 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 individuals with myelodysplastic syndromes.
 
Regulatory Status
 
On January 28, 2021, the Food and Drug Administration approved Romiplostim for adults and pediatric individuals (including term neonates) acutely exposed to myelosuppressive doses of radiation to increase survival.
 
Coding
 
See CPT/HCPCS Code section below.
 

Policy/
Coverage:
Effective August 15, 2023, prior approval is required for Romiplostim (e.g., Nplate).
 
Effective January 2024
 
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
 
Romiplostim meets member benefit primary coverage criteria that there be scientific evidence of effectiveness for individuals with immune thrombocytopenia when ALL the following criteria are met:
 
INITIAL APPROVAL STANDARD REVIEW for up to 6 months:
 
1. Individual has a diagnosis of ITP; AND
2. Individual is 1 year of age or older; AND
3. Individual has had an insufficient response to other treatment regimens that include corticosteroids, immunoglobulins, and/or splenectomy; AND
4. Individual has an initial (untransfused) platelet count less than 30 x 10 to the ninth power/L OR an initial plate count between 30 x 10 to the ninth power/L to 50 x 10 to the ninth power/L with symptomatic bleeding (e.g., significant mucous membrane bleeding, gastrointestinal bleeding or trauma) OR risk factors for bleeding (see policy guidelines); AND
5. If individual is < 18 years of age, then diagnosis of ITP has been present for at least six months; AND
6. Must be dosed in accordance with the FDA label.
 
CONTINUED APPROVAL for up to 1 year:
 
1. Individual has a diagnosis of ITP; AND
2. Individual is 1 year of age or older; AND
3. Must be dosed in accordance with the FDA label; AND
4. Documentation of platelet counts have shown improvement from baseline. Duration of authorization will be granted as follows:
a. Authorization of 3 months may be granted to members with current platelet count less than 50 x 10 to the ninth power/L for whom the platelet count is not sufficient to prevent clinically important bleeding and who have not received a maximal Nplate dose for at least 4 weeks: OR
b. Authorization of 12 months may be granted to members with current platelet count less than 50 x 10 to the ninth power/L for whom the current platelet count is sufficient to prevent clinically important bleeding; OR
c. Authorization of 12 months may be granted to members with current platelet count of 50 x 10 to the ninth power/L to 200 x 10 to the ninth/L; OR
d. Authorization of 12 months may be granted to members with current platelet count greater than 200 x 10 to the ninth power/L to less than or equal to 400 x 10 to the ninth power/L for whom Nplate dosing will be adjusted to achieve a platelet count sufficient to avoid clinically important bleeding.
 
Individuals with Hematopoietic Syndrome of Acute Radiation Syndrome
 
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
 
STANDARD REVIEW for up to one month for one dose.
 
Romiplostim meets member benefit primary coverage criteria that there be scientific evidence of effectiveness for individuals with hematopoietic syndrome of acute radiation syndrome to increase survival in adults and in pediatric individuals (including term neonates) acutely exposed to myelosuppressive doses of radiation (FDA, 2021) when dosed in accordance with the FDA label.
 
Limitations of Use:
 
1. Romiplostim is not indicated for the treatment of thrombocytopenia due to myelodysplastic syndrome (MDS) or any cause of thrombocytopenia other than ITP (FDA, 2021).
2. Romiplostim should be used only in individuals with ITP whose degree of thrombocytopenia and clinical condition increases the risk for bleeding (FDA, 2021).
3. Romiplostim should not be used in an attempt to normalize platelet counts (FDA, 2021).
 
Dosage and Administration
Dosing per FDA Guidelines
 
The recommended dose of Romiplostim is based on indication.
 
Romiplostim is available in 125mcg, 250mcg, or 500mcg lyophilized powder in a single-dose vial.
 
Romiplostim should be administered as a subcutaneous injection by a healthcare professional.
  
For Individuals with ITP (FDA, 2021):
 
Authorization will be given to allow up to 10 mcg/kg/week. Providers must dose in accordance with the FDA label.
 
1. The initial dose of Romiplostim is 1 mcg/kg. Actual body weight at initiation of treatment should always be used when calculating initial dose.
2. In adults, future dose adjustments are based on changes in platelet counts only.
3. In pediatric individuals, future dose adjustments are based on changes in platelet counts and changes in body weight. Reassessment of body weight is recommended every 12 weeks.
4. Adjust the weekly dose as follows based on platelet count:
a. If the platelet count is < 50 x 10 to the ninth power/L increase the dose by 1 mcg/kg.
b. If platelet count is > 200 x 10 to the ninth power/L and 400 x 10 to the ninth power/L for 2 consecutive weeks, reduce the dose by 1 mcg/kg.
c. If platelet count is > 400 x 10 to the ninth power/L, do not dose. Continue to assess the platelet count weekly. After the platelet count has fallen to < 200 x 10 to the ninth power/L, resume Nplate at a dose reduced by 1 mcg/kg.
5. Maximum dose of romiplostim is 10 mcg/kg/week.
6. Romiplostim should be discontinued if the platelet count does not increase to a level sufficient to avoid clinically significant bleeding after 4 weeks at the maximum dose of 10 mcg/kg/week.
 
For Adult and Pediatric Individuals (including term neonates) with hematopoietic syndrome of acute radiation syndrome (FDA, 2021):
 
The recommended dose of Romiplostim is 10 mcg/kg administered once as a subcutaneous injection. Administer the dose as soon as possible after suspected or confirmed exposure to radiation levels greater than 2 gray (Gy).
 
Policy Guidelines:
 
Examples of risk factors for bleeding (not all inclusive):
 
1. Undergoing a medical or dental procedure where blood loss is anticipated;
2. Mandated anticoagulation therapy.
 
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Romiplostim for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving outcomes, including but not limited to the following:
 
1. Romiplostim is not indicated for the treatment of thrombocytopenia due to myelodysplastic syndrome (MDS) or any cause of thrombocytopenia other than ITP (FDA, 2021).
2. Romiplostim should be used only in individuals with ITP whose degree of thrombocytopenia and clinical condition increases the risk for bleeding (FDA, 2021).
3. Romiplostim should not be used in an attempt to normalize platelet counts (FDA, 2021).
 
For members with contracts without primary coverage criteria, the use of Romiplostim in any indication or circumstance not described above is considered investigational, including but not limited to the following:
 
1. Romiplostim is not indicated for the treatment of thrombocytopenia due to myelodysplastic syndrome (MDS) or any cause of thrombocytopenia other than ITP (FDA, 2021).
2. Romiplostim should be used only in individuals with ITP whose degree of thrombocytopenia and clinical condition increases the risk for bleeding (FDA, 2021).
3. Romiplostim should not be used in an attempt to normalize platelet counts (FDA, 2021).
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
  
Effective May 2021 through December 2023
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Individuals with Immune Thrombocytopenia (ITP)
 
Treatment with romiplostim meets primary coverage criteria for effectiveness in improving health outcomes and is covered to decrease the risk of bleeding for individuals with chronic immune (idiopathic) thrombocytopenic purpura (ITP):
 
    1. In adult individuals when:
a. The initial platelet count is less than 50,000/ µL, AND
b. There is documented insufficient response to other treatment regimens that include corticosteroids, immunoglobulins, and/or splenectomy.
 
2. In pediatric individuals 1 year of age and older:
a. With ITP for at least 6 months (FDA, 2021) AND
b. There is documented insufficient response to other treatment regimens that include corticosteroids, immunoglobulins, or splenectomy(FDA, 2021)
 
Individuals with Hematopoietic Syndrome of Acute Radiation Syndrome
 
Treatment with romiplostim meets primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes to increase survival in adults and in pediatric individuals (including term neonates) acutely exposed to myelosuppressive doses of radiation (FDA, 2021) .
 
Limitations of Use:
 
1. Romiplostim is not indicated for the treatment of thrombocytopenia due to myelodysplastic syndrome (MDS) or any cause of thrombocytopenia other than ITP (FDA, 2021).
2. Romiplostim should be used only in individuals with ITP whose degree of thrombocytopenia and clinical condition increases the risk for bleeding (FDA, 2021).
3. Romiplostim should not be used in an attempt to normalize platelet counts (FDA, 2021).
 
Dosage and Administration
Dosing per FDA Guidelines
 
For Adult Individuals with ITP (FDA, 2021)
    • Initial dose of Romiplostim is 1 mcg/kg. Actual body weight at initiation of treatment should always be used when calculating the initial dose. In adults, future dose adjustments are based on changes in platelet counts only.
    • Adjust the weekly dose of Romiplostim by increments of 1 mcg/kg until the individual achieves a platelet count >50 X 109/L. Adjust as follows for adult individuals:
        • If the platelet count is < 50 × 109/L, increase the dose by 1 mcg/kg.
        • If platelet count is > 200 × 109/L and 400 × 109/L for 2 consecutive weeks, reduce the dose by 1 mcg/kg.
        • If platelet count is > 400 × 109/L, do not dose. Continue to assess the platelet count weekly. After the platelet count has fallen to < 200 × 109/L, resume Nplate at a dose reduced by 1 mcg/kg.
 
For Pediatric Individuals with ITP (FDA, 2021)
    • The initial dose of Romiplostim is 1 mcg/kg. Actual body weight at initiation of treatment should always be used when calculating initial dose. In pediatric individuals, future dose adjustments are based on changes in platelet counts and changes in body weight. Reassessment of body weight is recommended every 12 weeks.
    • Adjust the dose as follows for pediatric individuals:
        • If the platelet count is < 50 × 109/L, increase the dose by 1 mcg/kg.
        • If platelet count is > 200 × 109/L and 400 × 109/L for 2 consecutive weeks, reduce the dose by 1 mcg/kg.
        • If platelet count is > 400 × 109/L, do not dose. Continue to assess the platelet count weekly. After the platelet count has fallen to < 200 × 109/L, resume Nplate at a dose reduced by 1 mcg/kg.
 
For Adult and Pediatric Individuals (including term neonates) with hematopoietic syndrome of acute radiation syndrome (FDA, 2021)
    • The recommended dose of Romiplostim is 10 mcg/kg administered once as a subcutaneous injection. Administer the dose as soon as possible after suspected or confirmed exposure to radiation levels greater than 2 gray (Gy).
 
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
The use of romiplostim for any indication or circumstance other than listed above does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members with contracts without primary coverage criteria, the use of romiplostim for any indication or circumstance not listed above is considered investigational.  
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective April 2020 to April 2021
 
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):
 
    1. In adult patients 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.
 
2. In pediatric patients 1 year of age and older
        • With ITP for at least 6 months AND
        • There is documented insufficient response to other treatment regimens that include  corticosteroids, immunoglobulins, 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).
 
Dosage and Administration
 
      • Adjust the dose as follows for adult patients:
          • If the platelet count is < 50 × 109/L, increase the dose by 1 mcg/kg.
          • If platelet count is > 200 × 109/L and 400 × 109/L for 2 consecutive weeks, reduce the dose by 1 mcg/kg.
          • If platelet count is > 400 × 109/L, do not dose. Continue to assess the platelet count weekly. After the platelet count has fallen to < 200 × 109/L, resume Nplate at a dose reduced by 1 mcg/kg.
 
      • For Pediatric Patients with ITP
          • The initial dose of Nplate is 1 mcg/kg. Actual body weight at initiation of treatment should always be used when calculating initial dose. In pediatric patients, future dose adjustments are based on changes in platelet counts and changes in body weight. Reassessment of body weight is recommended every 12 weeks.
 
 
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
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 May 2019 to April 2020
 
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).
 
Dosage and Administration
 
Per FDA label guidelines
 
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
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 May 2013 to April 2019
 
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 Nplate 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.
 
2019 Update
A literature search conducted through April 2019 did not reveal any new information that would prompt a change in the coverage statement.
 
2020 Update
In a phase 3 double-blind study, eligible participants were children with immune thrombocytopenia aged 1 year to 17 years and mean platelet counts 30 × 10 9/L or less (mean of two measurements during the screening period) with no single count greater than 35 × 10 9/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 × 10 9/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 × 10 9/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. (Tarantino MD, Bussel JB, Blanchette VS, et al., 2016)
 
In a study of a thrombopoietic agent in children, patients with ITP of ≥ 6 months' duration were stratified by age 1:2:2 (12 months-< 3 years; 3-< 12 years; 12-< 18 years). Children received subcutaneous injections of romiplostim (n = 17) or placebo (n = 5) weekly for 12 weeks, with dose adjustments to maintain platelet counts between 50 × 10(9)/L and 250 × 10(9)/L. A platelet count ≥ 50 × 10(9)/L for 2 consecutive weeks was achieved by 15/17 (88%) patients in the romiplostim group and no patients in the placebo group (P = .0008). Platelet counts ≥ 50 × 10(9)/L were maintained for a median of 7 (range, 0-11) weeks in romiplostim patients and 0 (0-0) weeks in placebo patients (P = .0019). The median weekly dose of romiplostim at 12 weeks was 5 μg/kg. Fourteen responders received romiplostim for 4 additional weeks for assessment of pharmacokinetics. No patients discontinued the study. There were no treatment-related, serious adverse events. The most commonly reported adverse events in children, as in adults, were headache and epistaxis. In this short-term study, romiplostim increased platelet counts in 88% of children with ITP and was well-tolerated and apparently safe. The trial was registered with http://www.clinicaltrials.gov as NCT00515203. (Bussel JB, Buchanan GR, Nugent DJ, et al., 2011)
 
2021 Update
Wong K, Chang PY, Fielden M, et. al. (2019) evaluated the pharmacodynamics (PD) and pharmacokinetics (PK) of romiplostim alone and in combination with pegfilgrastim in a non-human primate (NHP) model of acute radiation syndrome (ARS). Male and female rhesus macaques were subjected to Cobalt-60 γ irradiation, at a dose of 550 cGy 24 h prior to subcutaneous administration of either romiplostim alone as a single (2.5 or 5.0 mg/kg on Day 1) or repeat dose (5.0 mg/kg on Days 1 and 8), pegfilgrastim alone as a repeat dose (0.3 µg/kg on Day 1 and 8), or a combination of both agents (romiplostim 5.0 mg/kg on Day 1; pegfilgrastim 0.3 µg/kg on Days 1 and 8). Clinical outcome, hematological parameters and PK were assessed throughout the 45 d study period post-irradiation.
 
Administration of romiplostim, pegfilgrastim or the combination of both resulted in significant improvements in hematological parameters, notably prevention of severe thrombocytopenia, compared with irradiated, vehicle control-treated NHPs. The largest hematologic benefit was observed when romiplostim and pegfilgrastim were administered as a combination therapy with much greater effects on both platelet and neutrophil recovery following irradiation compared to single agents alone.
 
These results indicate that romiplostim alone or in combination with pegfilgrastim is effective at improving hematological parameters in an NHP model of ARS. This study supports further study of romiplostim as a medical countermeasure to improve primary hemostasis and survival in ARS.
 
Efficacy studies of Nplate could not be conducted in humans with acute radiation syndrome for ethical and feasibility reasons. Approval for this indication was based on efficacy studies conducted in animals, Nplate’s effect on platelet count in healthy human volunteers and on data supporting Nplate’s effect on thrombocytopenia in patients with ITP and insufficient response to corticosteroids, immunoglobulins, or splenectomy.
 
Because of the uncertainty associated with extrapolating animal efficacy data to humans, the selection of a human dose for Nplate is aimed at providing platelet response to Nplate that is similar to that observed in efficacy studies conducted in animals. The recommended dose of Nplate for patients exposed to myelosuppressive doses of radiation is 10 mcg/kg administered once as a subcutaneous injection. The 10 mcg/kg dosing regimen for humans is based on population modeling and simulation analyses. For pediatric patients (including term neonates), extrapolation was based on data supporting Nplate’s effect on thrombocytopenia in patients with ITP and an insufficient response to corticosteroids, immunoglobulins, or splenectomy.
 
The safety of Nplate for the acute radiation syndrome setting was assessed based on the clinical experience in patients with ITP and from a study with healthy volunteers. The efficacy of Nplate was studied in a randomized, blinded, placebo-controlled study in a non-human primate model of radiation injury. Rhesus monkeys were randomized to either a control (n = 40) or treated (n = 40) cohort. Animals were exposed to total body irradiation (TBI) of 6.8 Gy from a Cobalt60 gamma ray source, representing a dose that would be lethal in 70% of animals by 60 days of follow-up (LD70/60). Animals were administered a single subcutaneous dose of blinded treatment (control article [sterile saline] or Nplate [5mg/kg]) 24 hours post-irradiation. The primary efficacy endpoint was survival. Animals received medical management consisting of intravenous or subcutaneous fluids, anti-ulcer medication, anti-emetic medication, analgesics, antimicrobials, and other support as required.
 
Nplate significantly (one-sided p = 0.0002) increased 60-day survival in the irradiated animals: 72.5% survival (29/40) in the Nplate group compared to 32.5% survival (13/40) in the control group. In the same study, an exploratory cohort of n=40 animals received Nplate (5mg/kg) on day 1 and pegfilgrastim (0.3mg/kg) on days 1 and 8 post-irradiation. Survival in this combined treatment group was 87.5% (95% CI: (73.2%, 95.8%)). (FDA, 2021)
 
2022 Update
Annual policy review completed with a literature search using the MEDLINE database through May 2022. No new literature was identified that would prompt a change in the coverage statement.
 
2023 Update
Annual policy review completed with a literature search using the MEDLINE database through May 2023. No new literature was identified that would prompt a change in the coverage statement.
 
2024 Update
Annual policy review completed with a literature search using the MEDLINE database through May 2024. No new literature was identified that would prompt a change in the coverage statement.

CPT/HCPCS:
J2796Injection, romiplostim, 10 micrograms

References: Bussel JB, Buchanan GR, Nugent DJ, et al.(2011) A randomized, double-blind study of romiplostim to determine its safety and efficacy in children with immune thrombocytopenia. Blood. 2011;118(1):28-36. doi:10.1182/blood-2010-10-313908

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

Food and Drug Administration.(2021) (2021) Nplate (romiplostim). Accessed September 29, 2021 at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125268s168lbl.pdf

Food and Drug Administration.(2021) Nplate (romiplostim). Accessed May 6, 2021 at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125268s168lbl.pdf

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

Nplate® (Romiplostim) Product Information. Thousand Oaks, CA: Amgen Inc.; May, 2021.

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

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;388(10039):45-54. doi:10.1016/S0140-6736(16)00279-8

Wong K, Chang PY, Fielden M, Downey AM, Bunin D, Bakke J, Gahagen J, Iyer L, Doshi S, Wierzbicki W, Authier S.(2020) Pharmacodynamics of romiplostim alone and in combination with pegfilgrastim on acute radiation-induced thrombocytopenia and neutropenia in non-human primates. Int J Radiat Biol. 2020 Jan;96(1):155-166. doi: 10.1080/09553002.2019.1625488. Epub 2019 Jun 21. PMID: 31216213.


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