INDICATIONS

Nplate® is a thrombopoietin receptor agonist indicated for the treatment of thrombocytopenia in adult patients with immune thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. Nplate® is indicated for the treatment of thrombocytopenia in pediatric patients 1 year of age and older with ITP for at least 6 months 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 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.

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Nplate® is the only weekly treatment that delivers the lasting stability chronic ITP demands1,2
In the final analysis of the long-term extension study
  • The majority of patients achieved a platelet response for 27 weeks or greater. The maximum number of weeks with a platelet response was 1843
Long-term extension study design (N = 292)4
  • Open-label, single-arm, extension study in patients with adult chronic immune thrombocytopenia (ITP)4
  • 292 adult patients enrolled from previous Nplate® clinical trials, regardless of whether they had received Nplate® in those trials4
  • Primary safety assessment: incidence of adverse events (AEs), including death, thrombosis, bleeding, abnormal laboratory values, and the incidence of neutralizing antibody formation4

Open-label, single-arm, extension study in adult chronic ITP patients4,*

Treatment Duration

1 to 277 weeks (mean: 110 weeks). Patients entered study at different times during the defined 277-week study period

Nplate® or placebo/standard of care (SOC) patients from prior Nplate® trials
Prior Nplate® patients:
continued on their same dose*
Prior placebo/SOC patients:
started on Nplate® 1 mcg/kg/wk*

Learn about dosing for once-weekly Nplate®. See more

*Given as a once-weekly subcutaneous injection. Patients who had been off Nplate® for 24 weeks or who had not previously received Nplate® initiated therapy at 1 mcg/kg. Dose adjustments were allowed to maintain platelet counts ≥50 x 109/L.1 The recommended starting dose for Nplate® is 1 mcg/kg and the maximum weekly dose is 10 mcg/kg. Please see Nplate® full Prescribing Information for complete dosing instructions, including guidelines for dose adjustments.4

Study enrollment and completion4
TREATMENT PERIOD
# of patients
> 24 weeks
271 patients (93%)
> 48 weeks
242 patients (83%)
> 96 weeks
117 patients (40%)
> 144 weeks
93 patients (32%)
> 192 weeks
53 patients (18%)
> 240 weeks
23 patients (8%)

291 patients received at least one dose of Nplate® during the rolling enrollment period4

  • During the 277-week study period, treatment duration varied due to study entry at different times and discontinuation (mean treatment was 110 weeks)
  • 8% (23/291) of patients were treated longer than 240 weeks

200 patients completed the study4

  • Completers were defined as those who were followed through the last study visit, regardless of whether they were still on treatment4
  • The most common reason for discontinuing the trial was withdrawn consent (25 patients)4
    • Other reasons included death while on study (15 patients); adverse events, alternative therapy, and other reasons (11 patients each); administrative decision (7 patients); noncompliance, protocol-specified criteria, and lost to follow-up (3 patients each); and pregnancy and protocol deviation (1 patient each)4
Study results: AEs did not increase in frequency or type with longer Nplate® drug exposure4

Long-term safety profile in open-label extension study4

AEs WITH NPLATE®
% of patients (n)
Serious treatment-related AEs
8% (24/291)
Thrombotic events
6.5% (19/291)
Bone marrow reticulin increase
1.4% (4/291)
Neutralizing antibodies
< 1% (2/291)
Deaths
5% (16/291)

25 thrombotic events were reported in 19 patients; 6 events were considered possibly treatment related.4

Bone marrow biopsies were performed at the discretion of the investigators. Forty bone marrow biopsies were performed in 38 patients. Some biopsies were also assessed for type 1 collagen and evidence of myeloproliferative disease, although none was observed. Of 11 patients with increased bone marrow reticulin, the investigator reported it as an AE in 4 patients.4

Two deaths were considered possibly treatment related, 1 due to myocardial infarction and 1 to unstable angina. Per the authors, there did not appear to be any relationship between the duration of romiplostim treatment or platelet count and the number or types of deaths during the study.4

The most common AEs included headache (38% of patients), nasopharyngitis (34%), fatigue (32%), contusion (31%), upper respiratory tract infection (26%), diarrhea (25%), and epistaxis (25%).4

5-year follow-up study established long-term safety, demonstrating no
increases in AEs or new AE types with longer Nplate® exposure4

Review the article for the Nplate® long-term safety study. Learn more

Open-label study evaluated changes in bone marrow morphology in adult chronic immune thrombocytopenia (ITP) patients1

Study design1

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 characteristics5

  • 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 limitations5

  • Lack of within-patient comparison over time
  • Study design was chosen to limit patient discontinuation due to repeated bone biopsies

Modified Bauermeister scale: quantification of bone marrow reticulin and collagen5

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 results

Progression of reticulin fiber formation of ≥ 2 grades or an increase to grade 4 presence of collagen were reported in 6.9% (9/131) of patients who were evaluable for bone marrow reticulin formation. In total, 1.5% (2/132) 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.5

Percentage of patients treated with romiplostim that had changes in collagen fibrosis or bone marrow reticulin formation5

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

Of the 9 patients who had increases of ≥ 2 on the modified Bauermeister scale, 1 had neutropenia detected by laboratory test, and 2 had adverse events of anemia.5

Access the Annals of Hematology publication. Read more

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 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.
Adverse Reactions
Adult ITP
  • In the placebo-controlled trials of adult ITP patients, headache was the most commonly reported adverse drug reaction, occurring in 35% of patients receiving Nplate® and 32% of patients receiving placebo. Adverse drug reactions in adults with a ≥ 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%).
  • The safety profile of Nplate® was similar across patients, regardless of ITP duration. The following adverse reactions (at least 5% incidence and at least 5% more frequent with Nplate® compared with placebo or standard of care) occurred in Nplate ® patients with ITP duration up to 12 months: bronchitis, sinusitis, vomiting, arthralgia, myalgia, headache, dizziness, diarrhea, upper respiratory tract infection, cough, nausea and oropharyngeal pain. The adverse reaction of thrombocytosis occurred with an incidence of 2% in adults with ITP duration up to 12 months.
Pediatric ITP
  • The most common adverse reactions experienced by ≥ 5% of patients receiving Nplate ® with ≥ 5% higher incidence in the Nplate® arm across the two placebo-controlled trials were contusion (41%), upper respiratory tract infection (31%), oropharyngeal pain (25%), pyrexia (24%), diarrhea (20%), rash (15%), and upper abdominal pain (14%).
  • In pediatric patients of age ≥ 1 year receiving Nplate® for ITP, adverse reactions with an incidence of ≥ 25% in the two randomized trials were: contusion (41%), upper respiratory tract infection (31%), and oropharyngeal pain (25%).
  • In a long-term, single arm, open label pediatric safety study, headache occurred in 78/203 patients (38%); the incidence rates of other adverse reactions were similar to those reported in the placebo-controlled studies.

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.

INDICATIONS

Nplate® is a thrombopoietin receptor agonist indicated for the treatment of thrombocytopenia in adult patients with immune thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. Nplate ® is indicated for the treatment of thrombocytopenia in pediatric patients 1 year of age and older with ITP for at least 6 months 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 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.

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 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®

References: 1. Nplate® (romiplostim) prescribing information, Amgen. 2. Kuter DJ, Bussel JB, Lyons RM, et al. Efficacy of romiplostim in patients with chronic immune thrombocytopenia purpura: a double-blind randomised controlled trial. Lancet. 2008;371:395-403. 3. Data on file, Amgen; Duration of Response;2017. Response; 2018. 4. Kuter DJ, Bussel JB, Newland A, et al. Long‑term treatment with romiplostim in patients with chronic immune thrombocytopenia: safety and efficacy. Br J Haematol. 2013;161:41. 5. 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(7):1077-1087.