Phase 3 Trial in Splenectomized Patients
Nplate®: A proven first-choice option in heavily pretreated patients refractory to splenectomy
- 93% (39/42) of splenectomized patients who received Nplate® had taken ≥ 3 prior treatments.[3]
A uniquely stringent primary endpoint[9]: 38% of Nplate® patients achieved a durable platelet response[6]
- A durable platelet response was the achievement of 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.[6]*†
- 38% (16/42) of Nplate® patients vs 0% (0/21) of patients in the control arm had a durable platelet response in a randomized 6-month, placebo-controlled trial of splenectomized patients (P = 0.0013).[3][6]
79% of patients refractory to splenectomy responded to Nplate®[6]
- Overall platelet response was defined as durable plus transient‡ rates of response.[6]
- In a 6-month, phase 3 clinical trial, 79% (33/42) of Nplate® patients achieved overall platelet response vs 0% (0/21) of patients in the control arm.[6]
*In the two phase 3 trials, patients could have doses of corticosteroids, azathioprine, or danazol adjusted during the first 12 weeks of the study. Adjustments to concomitant medications were not allowed after week 12. The durable platelet response endpoint was assessed during weeks 17–24, therefore, its assessment accounted for the potentially confounding impact of adjusting concomitant medications.[3][6]
†Patients already receiving ITP medical therapies at a constant dosing schedule were allowed to continue receiving these medical treatments throughout the trials. Rescue therapies (ie, corticosteroids, IVIG, platelet transfusions, and anti-D immunoglobulin) were permitted for bleeding, wet purpura, or if the patient was at immediate risk for hemorrhage.[6]
‡A transient platelet response was defined as four or more weekly platelet responses without a durable platelet response from week 2 to week 25, excluding platelet counts within 8 weeks of rescue therapy.[1][2]
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A sustained response that often allowed decreased use of concurrent ITP medications
Nplate® sustained control over 6 months.[3]
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 them.
Median weekly platelet count included all patients, even those receiving rescue therapy. Error bars indicate the range from the first to third quartiles. Light-blue line indicates platelet count of 50 x 109/L.
Significantly more Nplate® patients decreased their exposure to concurrent ITP therapies[6]*
*Patients already receiving ITP medical therapies at a constant dosing schedule were allowed to continue receiving these medical treatments throughout the trials. Rescue therapies (ie, corticosteroids, IVIG, platelet transfusions, and anti-D immunoglobulin) were permitted for bleeding, wet purpura or if the patient was at immediate risk of hemorrhage.[6]
†Reduction was defined as > 25% dose reduction. For multiple baseline concurrent therapies, at least one therapy with > 25% dose reduction was observed without an increase in other ITP therapies.[6]
‡Discontinuation was defined as discontinuation of all therapies for patients receiving multiple concomitant baseline therapies.[6]
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Nplate® reduced the need for rescue therapy during the 6-month trial[3][6]
- Rescue therapies included corticosteroids, IVIG, platelet transfusions, and anti-D immunoglobulin and were permitted for bleeding, wet purpura, or if the patient was at immediate risk for hemorrhage.[6]
- Percentage of patients using rescue therapy was more than 2-fold higher in the control arm vs the Nplate® arm.[3][6]
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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.
Important Safety Information
Risk of Progression of Myelodysplastic Syndromes to Acute Myelogenous Leukemia
- In Nplate® 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®. Nplate® should be used with caution in patients with ITP and chronic liver disease.
- 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.
Bone Marrow Reticulin Formation and Risk for Bone Marrow Fibrosis
- 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 study, one patient with ITP and hemolytic anemia developed marrow fibrosis with collagen during Nplate® therapy. Clinical studies are in progress to assess the risk of bone marrow fibrosis and clinical consequences with cytopenias.
- If new or worsening morphological abnormalities or cytopenia(s) occur, consider a bone marrow biopsy to include staining for fibrosis.
Worsened Thrombocytopenia after Cessation of Nplate®
- In clinical studies of patients with chronic ITP who had Nplate® discontinued, four of 57 patients developed thrombocytopenia of greater severity than was present prior to Nplate® therapy. This worsened thrombocytopenia resolved within 14 days.
- Following discontinuation of Nplate®, obtain weekly CBCs, including platelet counts, for at least 2 weeks and consider alternative treatments for worsening thrombocytopenia, according to current treatment guidelines.
Lack or 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 (1-800-772-6436). 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 studies, 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%).
Please see Prescribing Information and Medication Guide
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THE NPLATE® FIRST STEP™ PROGRAM
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Clinical studies have evaluated the safety and efficacy of Nplate® treatment in adult patients with chronic ITP. Nplate® clinical trials have been conducted in both splenectomized and non-splenectomized patients, with some patients receiving Nplate® treatment for > 5 years.
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