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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PRESCRIBING INFORMATION INDICATIONS IMPORTANT SAFETY INFORMATION VISIT PATIENT SITE

Established Safety Profile Without Food Restrictions

Nplate® is the once-weekly, in-office treatment that offers:

5 years

No new safety signals observed up to 5 years of continuous treatment1

No daily pill reminders

No need to remember to take a pill every day2-5

No liver monitoring required

No liver monitoring, and no known drug interactions or dietary restrictions2,6

Pivotal Trials (Pooled)

Adverse Reactions in Placebo-Controlled Phase 3 Trials2

Adverse drug reactions with ≥ 5% higher incidence with Nplate® vs placebo control

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 placebo2

Incidence of Bleeding Events*

Bleeding events were captured as adverse events and were not a predefined endpoint in the pivotal trial.2

Incidence of Grade 2 and above bleeding events across pivotal trials2

Incidence of grade 2 and above bleeding events across pivotal trials
  • Patients in the control arm received placebo. Some patients in both arms were receiving concurrent ITP medications at baseline and were allowed to continue receiving them2
  • Post hoc analysis showed that no bleeding events of Grade 2 or higher severity occurred at platelet counts > 50 x 109/L in these pivotal trials7

*Bleeding events Grade 2 through 5 were defined as follows: Grade 2 is moderate, causing enough discomfort to interfere with usual activity; Grade 3 is severe, incapacitating, making it impossible to work or engage in usual activities; Grade 4 is life-threatening, patient is at risk of death at the time of the event; Grade 5 is fatal.7

Long-Term Extension Data

Adverse Events (AEs) Did Not Increase in Frequency or Type With Longer Nplate® Drug Exposure1

Long-term safety profile in open-label extension study

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% (4/291)
Deaths 5% (16/291)
  • 25 thrombotic events were reported in 19 patients; 6 events were considered possibly treatment related1
  • 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 patients1
  • 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 study1

Most common AEs

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%).1

5-year follow-up study established long-term safety, demonstrating no increase in AEs or new AE types with longer Nplate® exposure1

Review the article for the Nplate® long-term safety study

CHANGES IN BM MORPHOLOGY

Nplate® Showed Minimal Changes in Reticulin Fiber Formation and Collagen Fibrosis8

  • 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

    – 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

  • 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

Percentage of patients treated with romiplostim that had changes in collagen fibrosis or bone marrow reticulin formation8

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

Evaluable change 6.9 percent

Presence of collagen (Grade 4 findings)

Evaluable change 1.5 percent

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.8

Access the <i>Annals of Hematology</i> publication

STUDY DESIGN & BASELINE CHARACTERISTICS

A Phase 4, Open-label, Multicenter Trial Evaluating Changes in BM Morphology2

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.2

Modified Bauermeister scale: quantification of bone marrow reticulin and collagen8

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)

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.2

Baseline characteristics8

  • 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 limitations8

  • Lack of within-patient comparison over time
  • Study design was chosen to limit patient discontinuation due to repeated bone biopsies
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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. Kuter DJ, Bussel JB, Newland A. Long-term treatment with romiplostim in patients with chronic immune thrombocytopenia: safety and efficacy. Br J Haematol. 2013;161(3):411-423. 2. Nplate® (romiplostim) prescribing information, Amgen. 3. Promacta® (eltrombopag) full Prescribing Information, Novartis. 4. Doptelet® (avatrombopag) full Prescribing Information, Sobi. 5. Tavalisse® (fostamatinib disodium hexahydrate) full Prescribing Information, Rigel. 6. Data on file, Amgen; Clinical Study Report 20080435; 2014. 7. Gernsheimer T. Chronic idiopathic thrombocytopenic purpura: mechanisms of pathogenesis. Oncologist. 2009;14(1):12-21. 8. 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. 2015;95(7):1077-1087.