Safety profile evaluated across multiple clinical trials11

 

Adverse reactions in placebo-controlled phase 3 trials11

Pivotal trials: adverse drug reactions with ≥ 5% higher incidence with Nplate® vs placebo control in phase 3 trials11

Adverse reactions Nplate® (n = 84) Control (n = 41)
Arthralgia 26% 20%
Dizziness 17% 0%
Insomnia 16% 7%
Myalgia 14% 2%
Pain in extremity 13% 5%
Abdominal pain 11% 0%
Shoulder pain 8% 0%
Dyspepsia 7% 0%
Paresthesia 6% 0%
Headache was the most commonly reported adverse drug reaction, occurring in 35% of patients receiving Nplate® and 32% of patients receiving placebo.11
Safety profile evaluated across multiple clinical trials11

Adverse reactions in placebo-controlled phase 3 trials11

Pivotal trials: adverse drug reactions with ≥ 5% higher incidence with Nplate® vs placebo control in phase 3 trials11

Adverse reactions Nplate® (n = 84) Control (n = 41)
Arthralgia 26% 20%
Dizziness 17% 0%
Insomnia 16% 7%
Myalgia 14% 2%
Pain in extremity 13% 5%
Abdominal pain 11% 0%
Shoulder pain 8% 0%
Dyspepsia 7% 0%
Paresthesia 6% 0%
Headache was the most commonly reported adverse drug reaction, occurring in 35% of patients receiving Nplate® and 32% of patients receiving placebo.11

Adverse event summary in Nplate® or standard of care (SOC) trial22

Nplate® or SOC trial: adverse event summary22,*

Adverse events Nplate® (n = 154) Control (n = 75)
Serious adverse events, % 23 37
Treatment-related serious adverse events, % 5 8
Total deaths (none treatment related), n 1 5
Thrombotic events, number of events (rate) 11
(0.15/100 patient-weeks)
2
(0.07/100 patient-weeks)
Hematologic malignancy, number of events 0 2
Lymphoma 0 1
Myelodysplastic syndrome 0 1
Most common adverse events33:
  • Nplate® arm: headache (35%), fatigue (27%), and nasopharyngitis (23%)
  • SOC arm: epistaxis (23%), nasopharyngitis (19%), and contusion (19%)

Adverse event summary in Nplate® or standard of care (SOC) trial22

Nplate® or SOC trial: adverse event summary22,*

Adverse events Nplate® (n = 154) Control (n = 75)
Serious adverse events, % 23 37
Treatment-related serious adverse events, % 5 8
Total deaths (none treatment related), n 1 5
Thrombotic events, number of events (rate) 11
(0.15/100 patient-weeks)
2
(0.07/100 patient-weeks)
Hematologic malignancy, number of events 0 2
Lymphoma 0 1
Myelodysplastic syndrome 0 1
Most common adverse events33:
  • Nplate® arm: headache (35%), fatigue (27%), and nasopharyngitis (23%)
  • SOC arm: epistaxis (23%), nasopharyngitis (19%), and contusion (19%)
Additional long-term safety data added to the Nplate® label1,41,4

 

Study design1,41,4

A phase 4, open-label, multicenter trial prospectively evaluated bone marrow for reticulin formation and collagen fibrosis in adult patients with immune thrombocytopenia (ITP) receiving Nplate® (romiplostim) or a non-US-approved romiplostim product. A modified Bauermeister grading scale was used for both assessments.

Patients were administered Nplate® by subcutaneous injection once weekly for up to 3 years. Based on cohort assignment at the time of study enrollment, patients were evaluated for bone marrow reticulin and collagen at year 1 (cohort 1), year 2 (cohort 2), or year 3 (cohort 3) in comparison to the baseline bone marrow at the start of the study. A total of 169 patients were enrolled in the 3 cohorts.

Baseline characteristics44

  • Mean age of 50 years
  • Median baseline platelet count was 23 x 109/L (range, 0.5–130 x 109/L)
  • 36% (60/169) of patients were splenectomized before enrollment

Study limitations44

  • Lack of within-patient comparison over time
  • Study design was chosen to limit patient discontinuation due to repeated bone biopsies
  • No placebo control group
  • Cohorts were not randomized, but enrolled sequentially to ensure adequate enrollment

Modified Bauermeister scale: quantification of bone marrow reticulin and collagen44

Grade 0 No reticulin
Grade 1 Occasional fine individual fibers and foci of a fine fiber network
Grade 2 Fine fiber network throughout most of the section; no coarse fibers
Grade 3 Diffuse fiber network with scattered thick coarse fibers but no mature collagen (negative trichrome staining)
Grade 4 Diffuse, coarse fiber network with areas of collagenization (positive trichrome staining)
Study results1,41,4

Progression of reticulin fiber formation of ≥ 2 grades or an increase to grade 4 presence of collagen were reported in 6.9% (9 of 131) of patients who were evaluable for bone marrow reticulin formation. In total, 1.5% (2 of 132) of patients with evaluable bone marrow collagen fibrosis developed collagen. There was no detectable collagen in the one patient who underwent repeat testing 12 weeks after discontinuation of romiplostim.

Percentage of patients treated with romiplostim that had changes in collagen fibrosis or bone marrow reticulin formation1,41,4

Progression of reticulin fiber formation ≥ 2 grades or an increase to grade 4 (presence of collagen)

Presence of collagen (grade 4 findings)

Percentage of patients treated with Nplate (romiplostim) who had changes in collagen fibrosis or bone marrow reticulin formation Percentage of patients treated with Nplate (romiplostim) who had changes in collagen fibrosis or bone marrow reticulin formation

Presence of collagen (grade 4 findings)

Percentage of patients treated with Nplate (romiplostim) who had changes in collagen fibrosis or bone marrow reticulin formation

Of the 9 patients who had increases of ≥ 2 on the modified Bauermeister scale, one had neutropenia detected by laboratory test, and two had adverse events of anemia.1,41,6

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Some information included in this article may not be consistent with the approved product labeling. For specific information regarding the approved use of Nplate®, see the full Prescribing Information.

*Rate = adverse event rate per 100 patient-weeks on study medication. Nplate® total patient-weeks = 7,294; SOC total patient-weeks = 3,050.22

Not considered treatment related by investigators.22

Important Safety Information

Risk of Progression of Myelodysplastic Syndromes to Acute Myelogenous Leukemia

  • In Nplate® (romiplostim) clinical trials of patients with myelodysplastic syndromes (MDS) and severe thrombocytopenia, progression from MDS to acute myelogenous leukemia (AML) has been observed.
  • Nplate® is not indicated for the treatment of thrombocytopenia due to MDS or any cause of thrombocytopenia other than chronic ITP.

Thrombotic/Thromboembolic Complications

  • Thrombotic/thromboembolic complications may result from increases in platelet counts with Nplate® use. Portal vein thrombosis has been reported in patients with chronic liver disease receiving Nplate®.
  • To minimize the risk for thrombotic/thromboembolic complications, do not use Nplate® in an attempt to normalize platelet counts. Follow the dose adjustment guidelines to achieve and maintain a platelet count of ≥ 50 x 109/L.

Loss of Response to Nplate®

  • Hyporesponsiveness or failure to maintain a platelet response with Nplate® should prompt a search for causative factors, including neutralizing antibodies to Nplate®.
  • To detect antibody formation, submit blood samples to Amgen (1‑800‑772‑64361‑800‑772‑6436). Amgen will assay these samples for antibodies to Nplate® and thrombopoietin (TPO).
  • Discontinue Nplate® if the platelet count does not increase to a level sufficient to avoid clinically important bleeding after 4 weeks at the highest weekly dose of 10 mcg/kg.

Laboratory Monitoring

  • Obtain CBCs, including platelet counts, weekly during the dose adjustment phase of Nplate® therapy and then monthly following establishment of a stable Nplate® dose.
  • Obtain CBCs, including platelet counts, weekly for at least two weeks following discontinuation of Nplate®.

Adverse Reactions

  • In the placebo-controlled trials, headache was the most commonly reported adverse drug reaction, occurring in 35% of patients receiving Nplate® and 32% of patients receiving placebo. Headaches were usually of mild or moderate severity.
  • Most common adverse reactions (≥ 5% higher patient incidence in Nplate® versus placebo) were Arthralgia (26%, 20%), Dizziness (17%, 0%), Insomnia (16%, 7%), Myalgia (14%, 2%), Pain in Extremity (13%, 5%), Abdominal Pain (11%, 0%), Shoulder Pain (8%, 0%), Dyspepsia (7%, 0%), and Paresthesia (6%, 0%).
  • Nplate® administration may increase the risk for development or progression of reticulin fiber formation within the bone marrow. This formation may improve upon discontinuation of Nplate®. In a clinical trial, one patient with ITP and hemolytic anemia developed marrow fibrosis with collagen during Nplate® therapy.


Women who become pregnant during Nplate® treatment are encouraged to enroll in Amgen's Pregnancy Surveillance Program. Patients or their physicians should call 1‑800‑77‑AMGEN1‑800‑77‑AMGEN (1‑800‑772‑64361‑800‑772‑6436) to enroll.

Indication

Nplate® is a thrombopoietin receptor agonist indicated for the treatment of thrombocytopenia in patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.

Nplate® is not indicated for the treatment of thrombocytopenia due to myelodysplastic syndrome (MDS) or any cause of thrombocytopenia other than chronic ITP. Nplate® should be used only in patients with ITP whose degree of thrombocytopenia and clinical condition increase the risk for bleeding. Nplate® should not be used in an attempt to normalize platelet counts.

Please see full Prescribing Information and Medication Guide.

See More Close

Important Safety Information

Risk of Progression of Myelodysplastic Syndromes to Acute Myelogenous Leukemia

  • In Nplate® (romiplostim) clinical trials of patients with myelodysplastic syndromes (MDS) and severe thrombocytopenia, progression from MDS to acute myelogenous leukemia (AML) has been observed.
  • Nplate® is not indicated for the treatment of thrombocytopenia due to MDS or any cause of thrombocytopenia other than chronic ITP.

Thrombotic/Thromboembolic Complications

  • Thrombotic/thromboembolic complications may result from increases in platelet counts with Nplate® use. Portal vein thrombosis has been reported in patients with chronic liver disease receiving Nplate®.
  • To minimize the risk for thrombotic/thromboembolic complications, do not use Nplate® in an attempt to normalize platelet counts. Follow the dose adjustment guidelines to achieve and maintain a platelet count of ≥ 50 x 109/L.

Loss of Response to Nplate®

  • Hyporesponsiveness or failure to maintain a platelet response with Nplate® should prompt a search for causative factors, including neutralizing antibodies to Nplate®.
  • To detect antibody formation, submit blood samples to Amgen (1‑800‑772‑64361‑800‑772‑6436). Amgen will assay these samples for antibodies to Nplate® and thrombopoietin (TPO).
  • Discontinue Nplate® if the platelet count does not increase to a level sufficient to avoid clinically important bleeding after 4 weeks at the highest weekly dose of 10 mcg/kg.

Laboratory Monitoring

  • Obtain CBCs, including platelet counts, weekly during the dose adjustment phase of Nplate® therapy and then monthly following establishment of a stable Nplate® dose.
  • Obtain CBCs, including platelet counts, weekly for at least two weeks following discontinuation of Nplate®.

Adverse Reactions

  • In the placebo-controlled trials, headache was the most commonly reported adverse drug reaction, occurring in 35% of patients receiving Nplate® and 32% of patients receiving placebo. Headaches were usually of mild or moderate severity.
  • Most common adverse reactions (≥ 5% higher patient incidence in Nplate® versus placebo) were Arthralgia (26%, 20%), Dizziness (17%, 0%), Insomnia (16%, 7%), Myalgia (14%, 2%), Pain in Extremity (13%, 5%), Abdominal Pain (11%, 0%), Shoulder Pain (8%, 0%), Dyspepsia (7%, 0%), and Paresthesia (6%, 0%).
  • Nplate® administration may increase the risk for development or progression of reticulin fiber formation within the bone marrow. This formation may improve upon discontinuation of Nplate®. In a clinical trial, one patient with ITP and hemolytic anemia developed marrow fibrosis with collagen during Nplate® therapy.

Women who become pregnant during Nplate® treatment are encouraged to enroll in Amgen's Pregnancy Surveillance Program. Patients or their physicians should call 1‑800‑77‑AMGEN1‑800‑77‑AMGEN (1‑800‑772‑64361‑800‑772‑6436) to enroll.

Indication

Nplate® is a thrombopoietin receptor agonist indicated for the treatment of thrombocytopenia in patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.

Nplate® is not indicated for the treatment of thrombocytopenia due to myelodysplastic syndrome (MDS) or any cause of thrombocytopenia other than chronic ITP. Nplate® should be used only in patients with ITP whose degree of thrombocytopenia and clinical condition increase the risk for bleeding. Nplate® should not be used in an attempt to normalize platelet counts.

Please see full Prescribing Information and Medication Guide.

References: 1. Nplate® (romiplostim) prescribing information, Amgen. 2. Kuter DJ, Rummel M, Boccia R, et al. Romiplostim or standard of care in patients with immune thrombocytopenia. N Engl J Med. 2010;363:1889-1899. 3. Rummel M, Boccia R, Macik G, et al. Efficacy and safety of romiplostim versus medical standard of care as chronic therapy for nonsplenectomized patients with immune thrombocytopenia (ITP). Haematologica. 2009;94(suppl 2):425. Abstract 1059. Presented at: 14th Congress of the European Hematology Association; June 7, 2009; Berlin, Germany. 4. Janssens A, Rodeghiero F, Anderson D, et al. Changes in bone marrow morphology in adults receiving romiplostim for the treatment of thrombocytopenia associated with primary immune thrombocytopenia. Ann Hematol. 2016;95:1077-1087.

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