Frequently Asked Questions About Nplate^®

• 1. Where does Nplate^® fit within the treatment algorithm of chronic ITP?

  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.

  Recent expert publications concur that Nplate^® has proven efficacy in patients with chronic ITP, and provide recommendations for TPO-receptor agonists, including Nplate^®, as second-line treatment options for ITP.^[10][17]

  • — According to the American Society of Hematology ITP guideline update^[17]:
  • • “We recommend: Thrombopoietin receptor agonists for patients at risk of bleeding who relapse after splenectomy or who have a contraindication to splenectomy and who have failed at least one other therapy.”
    • “We suggest: Thrombopoietin-receptor agonists may be considered for patients at risk of bleeding who have failed one line of therapy such as corticosteroids or IVIg and who have not had splenectomy.”
    • “Strong recommendations are usually indicated by the phrase ‘we recommend…’ and weak recommendations by the phrase ‘we suggest…’.”
  • — According to the International ITP Consensus Report (ICR)^[17]*:
  • • Nplate^® is part of the ICR Grade A recommendation for the TPO-receptor agonist class as
      second-line treatment.
    • The grade A recommendation is defined as a standard of evidence that requires at least one randomized, controlled trial as part of a body of literature of overall good quality and consistency.
    • The graded rating system is not meant to imply comparison of safety or efficacy of the treatments, but rather to describe various levels of evidence.

  • *Amgen Ltd. was among the sponsors of the International ITP Consensus Report.

  • Review Nplate^® Clinical Efficacy Data

• 2. For how long was Nplate^® followed in a clinical trial to assess safety?

  Patients who participated in a prior phase 1, 2, or 3 romiplostim study were eligible to enroll in the open-label extension study. They received Nplate^® with weekly dosing based on platelet counts.^[2][24] One hundred phase 3 patients were entered into the open-label extension study, and by August 2008, had a median treatment duration of 60 weeks with a maximum duration of 96 weeks.^[6]

  By December 2010, 292 adult patients from a prior phase 1, 2, or 3 study had received Nplate^® in the ongoing open-label extension trial up to 5.3 years. The median duration of treatment was 78 weeks, and some were treated for up to 277 weeks. Nplate^® therapy was generally well tolerated for up to 5 years; 3.8% (11/292) of patients discontinued due to adverse events. In this study, adverse events did not increase in frequency with longer drug exposure. The most common adverse events were headache (38% of patients), nasopharyngitis (34%), and fatigue (32%).^[2][4]

  Click here to review Important Safety Information.

  Click here for more information on the long-term extension trial with Nplate^®

• 3. What are some of the important risks for Nplate^® as described in the Prescribing Information?

  Nplate^® is associated with a number of important risks. Please see below for an overview of these risks and click here to see Important Safety Information for Nplate^®

  • — 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.
  • — Additional serious adverse reactions associated with Nplate^® are Thrombotic/Thromboembolic Complications, Bone Marrow Reticulin Formation and Risk for Bone Marrow Fibrosis, Worsened Thrombocytopenia after Cessation of Nplate^®, and Lack or Loss of Response to Nplate^®.

• 4. Where is Nplate^® metabolized?

  The elimination of the Nplate^® peptibody is in part dependent on the TPO receptor found on platelets and megakaryocytes. The clearance of Nplate^® is through the reticuloendothelial system.^[6]

• 5. How quickly will Nplate^® work, and when will a response be apparent?

  Individual result will vary. In phase 3 clinical trials with Nplate^®, platelet response occurred within 1 to 3 doses in the majority of patients. Time to first platelet response was defined as scheduled visit week of first platelet count ≥ 50 x 10⁹/L.^[1][3][6] Click here to review Nplate^® clinical data.

• 6. What if a patient misses or comes late for a dose? What should Nplate^® patients do if or when they travel and cannot visit their physician for their weekly dose of Nplate^®?

  If patients miss a scheduled dose of Nplate^®, they should call their healthcare provider to arrange for their next dose as soon as possible.^[6] If a patient plans to travel, a healthcare provider or a patient can call My Nplate^® Center in advance at 1-855-MYCENTER (1-855-692-3683), and a patient support specialist will assist the patient or healthcare provider to find a doctor who can give the patient their Nplate^® injection at their destination. Please note that Amgen does not endorse or recommend any healthcare provider. The patient should make his or her own decision regarding their treatment options. Click here to learn more about My Nplate^® Center.

• 7. Which patients would be most suited for Nplate^® therapy?

  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.

  You can review patient profiles to help associate one of your chronic ITP patients with one or more patient types who might be appropriate for Nplate^®. Click here to learn more about appropriate patient types for Nplate^® .

Have additional questions about Nplate^®? Talk with a live representative

• 8. What happens to platelet counts when a patient stops taking 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 two weeks and consider alternative treatments for worsening thrombocytopenia, according to current treatment guidelines.^[6] Click here to learn more about discontinuation of Nplate^® treatment.

• 9. How do I re-start an Nplate^® patient if they have stopped?

  Reinitiate treatment with Nplate^® in accordance with dosing and administration recommendations.^[6]

• 10. What resources are available for patients interested in or currently taking Nplate^®?

  Patients can visit www.nplate.com to access a wide range of information on ITP and Nplate^® including printable materials. In addition, patients can link to other ITP sites, including the ITP Foundation and the Platelet Disorder Support Association. Amgen also provides healthcare professionals with printed materials to provide to patients getting started on Nplate^® therapy. To obtain these materials, healthcare professionals can call 1-877-NPLATE5 (1-877-675-2835) or contact their local Nplate^® representative. Or, click here to speak with a live representative now.

• 11. Is financial assistance available for patients taking Nplate^®?

  The Nplate FIRST STEP™ program provides comprehensive co-pay coupon assistance for qualifying, commercially insured ITP patients to help with their out-of-pocket expenses. To determine if patients meet the eligibility requirements or for more information regarding program restrictions and limitations, please call 1-888-65-STEP1 (1-888-657-8371) or go online to www.AmgenFIRSTSTEP.com. Amgen reserves the right to cancel or modify this program at any time.

  There are several other assistance programs available for patients taking Nplate^®. For information on these programs, click here to speak with a live representative now.

• 12. How is Nplate^® administered and dosed?

  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^®.^[6] Please see full Prescribing Information for complete dosing and administration instructions.^[6] Click here to learn more about Nplate^® dosage and administration.

• 13. How frequently should patients receiving Nplate^® have platelet counts monitored?

  During Nplate^® therapy, assess CBCs, including platelet counts, weekly until a stable platelet count (≥ 50 x 10⁹/L for at least 4 weeks without dose adjustment) has been achieved. Obtain CBCs, including platelet counts, monthly thereafter.^[6] Click here to learn more about Nplate^® dosage and administration.

• 14. How long should I tell my patients they should expect to stay on Nplate^®?

  Nplate^® should be given for as long as the healthcare provider and patient determine is necessary. Patients who had participated in the phase 3 studies were withdrawn from Nplate^® or placebo after 24 weeks. If platelet counts subsequently decreased to ≤ 50 x 10⁹/L, the patients were eligible for enrollment in an open-label extension study in which they would receive Nplate^® with weekly dosing based on platelet counts. Following Nplate^® discontinuation in the phase 3 studies, seven patients maintained platelet counts of ≥ 50 x 10⁹/L.^[6]

  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 two weeks and consider alternative treatments for worsening thrombocytopenia, according to current treatment guidelines.^[6]

• 15. Should Nplate^® be used in pregnant women?

  Pregnancy Category C: There are no adequate and well-controlled studies of Nplate^® use in pregnant women. In animal reproduction and developmental toxicity studies, romiplostim crossed the placenta, and adverse fetal effects included thrombocytosis, postimplantation loss, and an increase in pup mortality. Nplate^® should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.

  Pregnancy Registry: A pregnancy registry has been established to collect information about the effects of Nplate^® use during pregnancy. Physicians are encouraged to register pregnant patients, or pregnant women may enroll themselves in the Nplate^® pregnancy registry by calling 1-800-77-AMGEN (1-800-772-6436).