The United States Food and Drug Administration (FDA) has approved the thrombopoietin receptor agonist Nplate® (romiplostim) for the treatment of adults with chronic idiopathic thrombotic purpura (ITP) that does not sufficiently respond to corticosteroids, immunoglobins, or splenectomy. Nplate represents a significant breakthrough for patients with refractory chronic ITP, a patient population whose treatment options were limited.

At present, approximately 140,000 patients are being treated for chronic ITP in the United States and Europe. The treatment goal for the management of ITP is often to achieve a hemostatic platelet count in order to reduce the risk of bleeding events. Patients with ITP suffer platelet destruction as well as the inability to compensate for low levels of platelets, resulting in dangerously low platelet levels.

Nplate is the first thrombopoietin receptor agonist approved for ITP. It is composed of several copies of the TPO receptor-binding peptide spliced into a recombinant antibody. This peptide agonist competes with TPO for binding to the TPO receptor and activates the receptor in an identical fashion to endogenous TPO (eTPO). However, the peptide portion of Nplate has no amino acid sequence homology to eTPO, mitigating the risk of development of antibodies to therapy.

There were two clinical trials prompting the approval of Nplate. The two trials were randomized, placebo-controlled, double-blind studies that were identical in design, with the exception that one trial included splenectomized patients, while the second trial did not include patients who had undergone splenectomy. Patients in the trials had chronic ITP and had completed at least one prior treatment including corticosteroids, immunoglobulin’s, rituximab, cytotoxic therapies, danazol, and azathioprine. Patients had a platelet count of ≤ 30 x 109/L prior to study entry and were randomized (2:1) to 24 weeks of Nplate (1 mcg/kg subcutaneous [SC]) or placebo. Patients already receiving ITP medical therapies at a constant dosing schedule were allowed to continue receiving these medical treatments throughout the studies. Rescue therapies (for example, corticosteroids, IVIG, platelet transfusions, and anti-D immunoglobulin) were permitted for bleeding, wet purpura, or if the patient was at immediate risk for hemorrhage.

Patients received single weekly SC injections of Nplate with individual dose adjustments to maintain platelet counts (50 x 109/L to 200 x 109/L).

• Among non-splenectomized patients platelet responses were achieved in 88% of those treated with Nplate compared with 14% for those who received placebo.

• Among splenectomized patients platelet responses were achieved in 49% of patients treated with Nplate compared with 0% of those who received placebo.

• Serious bleeding was reported in 6% of patients treated with Nplate and 10% of those who received placebo.

• The most common adverse event reported was headache, the incidence of which was similar between the Nplate and placebo groups. The most common adverse events that occurred with a 5% or greater frequency in the Nplate arm over the placebo arm were arthralgia, dizziness, insomnia, and myalgia.

Among patients receiving concurrent medications, the following results were achieved:

• Among non-splenectomized patients 36% of those treated with Nplate were able to reduce the need for concurrent therapy and 36% were able to completely discontinue concurrent therapy versus only 20% and 30%, respectively, of those who received placebo.

• Among splenectomized patients 33% of those treated with Nplate were able to reduce the need for concurrent therapy and 67% were able to completely discontinue therapy versus 17% and 0%, respectively.

• Total reduction and discontinuation of concomitant therapy for Nplate patients in the non-splenectomized study was 73% versus 50% of placebo patients.

• Total reduction and discontinuation of concomitant therapy for Nplate in the splenectomized study was 100% versus 17% of placebo patients.

Nplate is to be used to treat patients whose levels of thrombocytopenia or clinical condition place them at risk for severe bleeding. Nplate is not to be used with the intent of normalizing platelet counts among patients with mild thrombocytopenia or in patients with myelodysplastic syndromes (MDS).

For prescribing Nplate physicians are required to provide a patient-friendly medication guide through the Nplate NEXUS Program. Information on the NEXUS program can be found by calling 1-877-NPLATE1 (1-877-675-2831), or by visiting www.nplate.com.

Reference: Nplate Prescribing Information. Available at: http://www.nplate.com/pdfs/misc/nplate_pi.pdf. Accessed September 2008