Phase 3 Trial in Non-splenectomized Patients
Nplate®: Proven response in non-splenectomized patients
A uniquely stringent primary endpoint[9]: 61% 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]*†
- 61% (25/41) of Nplate® patients vs 5% (1/21) of patients in the control arm had a durable platelet response in a randomized 6-month, placebo-controlled trial in non-splenectomized patients (P < 0.0001).[3][6]
88% of Nplate® patients achieved overall platelet response[6]
- Overall platelet response was defined as durable plus transient rates of platelet response.[6]
- In a 6-month, phase 3 clinical trial, 88% (36/41) of Nplate® patients achieved an overall platelet response vs 14% (3/21) 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, enabling assessment of the Nplate® response without the potentially confounding impact of adjusting concomitant medications.[3][6]
†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]
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Platelet response occurred within1–3 doses
73% of Nplate® patients responded within 1–3 doses[1][3]
- Patients continued to receive weekly doses of Nplate®.[1][3]
- 63% (26/41) of non-splenectomized patients randomized to Nplate® had received ≤ 2 prior ITP treatments.[1]
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.
Time to first platelet response was defined as scheduled visit week of first platelet count ≥ 50 x 109/L.
Sustained response
Nplate® maintained response throughout the phase 3 trial[3]
- Non-splenectomized patients had experienced failed corticosteroid treatments and the ups and downs of rescue medications prior to receiving Nplate®.[3]
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.
Reduced moderate, severe, and life-threatening bleeding events
Low incidence of grade 2 and above bleeding events with Nplate® vs control[25]
All grade ≥ 2 bleeding events except one were at platelet counts ≤ 20 x 109/L, and all ≥ grade 3 bleeding events were at platelet counts ≤ 20 x 109/L.[25]
No bleeding events of grade 2 or higher severity occurred at platelet counts > 50 x 109/L.[25]
Definitions of bleeding events grades 2 through 5[25]*
Grade 2: moderate; caused enough discomfort to interfere with usual activity
Grade 3: severe; incapacitating, making it impossible to work or engage in usual activities
Grade 4: life-threatening; patient was at risk of death at the time of the event
Grade 5: fatal
Bleeding events were captured as adverse events and were not a predefined endpoint in the pivotal trial.[2][25]
*Grading was per the Common Terminology Criteria for Adverse Events, v3. http://ctep.cancer.gov.
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Reduced patients’ exposure to immunosuppressants
Nplate® reduced the need for concurrent ITP therapies[6]
- 36% (4/11) of Nplate® patients were able to reduce concurrent medications, compared with 20% (2/10) of control patients.[6]
- 36% (4/11) of Nplate® patients were able to discontinue concurrent medications, compared with 30% (3/10) of control patients.[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]
8 in 10 patients on Nplate® did not require rescue therapy throughout 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 3-fold higher in the control arm vs the Nplate® arm.[3][6]
In addition to these pivotal phase 3 trial results, a phase 3b trial was conducted in non-splenectomized patients to evaluate Nplate® and medical standard of care (SOC) for treatment of ITP in adults.[5] Click here to review the data now.
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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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