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® pivotal trials1

The pivotal trials consisted of two phase 3, parallel, double-blind studies where patients with chronic immune thrombocytopenia (ITP) who had completed at least one prior treatment were randomized to Nplate® or placebo. The primary endpoint was the achievement of a durable platelet response, defined as a weekly platelet count ≥ 50 x 109/L for at least 6 of the last 8 weeks of the 24-week treatment period in the absence of rescue therapies at any time.1,2



See the Nplate® pivotal trials information. Learn more

In the Nplate® or standard of care (SOC) trial, patients treated with Nplate® had a significantly reduced incidence of treatment failure and bleeding events vs SOC therapies3

Study design
Efficacy
Safety
STUDY DESIGN

Nplate® or SOC trial design (N = 234)3

Treatment with Nplate® or SOC was studied in a multicenter, randomized, controlled, 52-week, open-label evaluation of Nplate® and medical SOC therapy for non-splenectomized patients with ITP.3

The design of this trial does not allow for comparison of Nplate® to the individual treatments received in the SOC arm.3

  • Co-primary endpoints were the incidence of treatment failure and splenectomy
  • Safety outcomes were measured as one of the secondary endpoints
  • Concomitant therapies were allowed for both treatment groups
  • To achieve a target platelet count of 50–200 x 109/L, Nplate® was administered once weekly at a starting dose* of 3 mcg/kg up to a maximum dose of 10 mcg/kg
  • Treatments for patients assigned to the SOC group were selected by the investigator according to standard institutional practices or therapeutic guidelines

*The recommended starting dose for Nplate® is 1 mcg/kg. Please see Nplate® Prescribing Information for complete dosing instructions, including guidelines for dose adjustments. In the pivotal trials, the median dose of Nplate® was 2 mcg/kg (25th-75th percentile: 1-3 mcg/kg) in the study of non-splenectomized patients and 3 mcg/kg (25th-75th percentile: 2-7 mcg/kg) in the study of splenectomized patients.1

Co-primary Endpoints
1. incidence of treatment failure
Study discontinuation before treatment failure
was also considered treatment failure.
Platelet count
≤ 20 x 109/L for 4 consecutive weeks at highest recommended dose of study treatment
Major bleeding event
Change in treatment
due to side effects or bleeding symptoms
TREATMENT FAILURE
2. Incidence of Splenectomy
Study discontinuation before splenectomy
was also considered splenectomy.
Therapies used in SOC arm3
Patients could receive one or more
types of SOC therapies, including
watchful waiting3

Patients already receiving ITP therapies at baseline (21/157 in Nplate® group; 5/77 in SOC group) could continue receiving these throughout the trial.3

Other ITP treatments used in the Nplate® arm at any time during the 1-year trial included corticosteroids (37% of patients), immunoglobulins (7%), rituximab (1%), azathioprine (1%), danazol (2%), other medications† (6%), and platelet transfusions (6%).3

*Rituximab is not FDA approved for use in ITP.4

†Including vincristine, cyclosporine, tranexamic acid, ascorbic acid, calcium, ethamsylate, pantoprazole, and Expasyl®.3 Expasyl is a registered trademark and entire property of Pierre Rolland.

EFFICACY
Nplate® or SOC trial results
Reduce treatment failure vs SOC therapies
Incidence of treatment failure at 1 year3
Approximately 9 out of 10 non-splenectomized patients in the Nplate® arm did not experience treatment failure3

Results were consistent with those in pivotal phase 3 trial non-splenectomized patients.1

The percentage of patients on Nplate® achieving a platelet response (≥ 50 x 109/L) ranged from 71% (108/152) to 92% (127/138) at any scheduled visit (weeks 2-52).3

Review Nplate® or SOC trial safety information. Learn more

Raise and sustain platelet counts in splenectomized patients1

Deliver platelet stability and durability1

Sustained median platelet count ≥ 50 x 109/L1,2

Median weekly platelet count includes all patients, even those receiving rescue therapy. Error bars indicate the range from the first to the third quartiles. Light-blue line indicates platelet count of 50 x 109/L.2

Comparable results were seen in non-splenectomized patients.2

Reduce the potential for bleeding events3
Rate of grade 3 and above bleeding events3,5

Rate = adverse event rate per 100 patient-weeks on study medication. Rate was calculated by dividing the total number of reported events by the total number of patient-weeks and then multiplying by 100.3

Definitions of bleeding events grade 2 through 53

GRADE 2
Moderate
GRADE 3
Severe
GRADE 4
Life-threatening
GRADE 5
Fatal

In the pivotal trial with non-splenectomized patients, 10% (4/42) of Nplate® patients vs 30% (6/20) of control patients experienced a grade 2* or above bleeding event.5 Bleeding events were captured as adverse events and were not a predefined endpoint in the pivotal trial.

*Grading was per the Common Terminology Criteria for Adverse Events, v3. http://ctep.cancer.gov

SAFETY
The safety profile of Nplate® was consistent
across clinical trial results

Nplate® or SOC trial: adverse event summary3

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 events6
  • Nplate® arm: headache (35%), fatigue (27%), and nasopharyngitis (23%)
  • SOC arm: epistaxis (23%), nasopharyngitis (19%), and contusion (19%)

Rate = adverse event rate per 100 patient-weeks on study medication. Nplate® total patient-weeks = 7,294; SOC total patient-weeks = 3,050.3

*Not considered treatment related by investigators.3

The safety profile of Nplate® was consistent across clinical trials1,2

Nplate® or SOC trial: adverse event summary2*
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 events3:
  • Nplate® arm: headache (35%), fatigue (27%), and nasopharyngitis (23%)
  • SOC arm: epistaxis (23%), nasopharyngitis (19%), and contusion (19%)
NEXT See Health-related Quality of Life data

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. 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. 4. RITUXAN® (rituximab) full Prescribing Information, Genentech, Inc. 5. Gernsheimer TB, George JN, Aledort LM, et al. Evaluation of bleeding and thrombotic events during long-term use of romiplostim in patients with chronic immune thrombocytopenia (ITP). J Thromb Haemost. 2010;8(6):1372-1382. 6. Rummel M, Boccia R, Macik G, et al. Efficacy and safety of romiplostim versus medical standard of care as chronic therapy for nonsplenectomised patients with immune thrombocytopenia (ITP). Haematologica. 2009;94(suppl 2):424.