Evaluation of AMG 531 Efficacy in Nonsplenectomized Patients with Chronic Immune Thrombocytopenic Purpura (ITP) in a Randomized Placebo-Controlled Phase 3 Study.

AMG 531 is a novel platelet-stimulating peptibody that stimulates the thrombopoietin (TPO) receptor, and is being studied for its ability to increase production of platelets. Here we report efficacy data in nonsplenectomized patients from a randomized, double blind, placebo-controlled Phase 3 study designed to evaluate the efficacy and safety of AMG 531 in patients with chronic ITP. Sixty-two nonsplenectomized patients were enrolled (placebo, 21; AMG 531, 41) with a median age of 52 years (range 21 to 88) and a mean baseline platelet count of 18.3x10⁹/L. Subcutaneous AMG 531 or placebo was administered weekly for 24 weeks at a starting dose of 1μg/kg, and adjusted to maintain a target platelet count of 50-200x10⁹/L. One patient randomized to placebo received 3 doses of AMG 531 in error and was included in the efficacy analysis as a placebo. The primary study endpoint was the incidence of a durable platelet response, defined as a platelet count ≥50x10⁹/L for ≥6 weeks during the last 8 weeks of the 24-week treatment period in the absence of rescue medications. Starting at a low dose of AMG 531 and gradually increasing it, as well as reducing the dose of steroids in certain patients, contributed to lower platelet counts early in the study. Twenty-five of the 41 patients (61.0%) receiving AMG 531 achieved a durable platelet response compared to 1/21 (4.8%) receiving placebo (p<0.0001). Overall response, defined as either durable or transient platelet response (≥4 weekly platelet responses), was observed in 36/41 (87.8%) patients receiving AMG 531, but was observed in only 3/21 (14.3%) placebo patients. The mean number of weekly platelet responses (platelet count ≥50x10⁹/L) was significantly greater in patients receiving AMG 531 (15.2/24 weeks, 63%) compared to placebo (1.3/24 weeks, 5%) (p<0.0001). AMG 531 reduced the proportion of patients requiring ITP rescue medications, defined as either increase from baseline in dose of concurrent ITP medication or use of new medication to increase platelet counts. Thirteen of 21 (61.9%) placebo-treated patients received rescue medications compared to just 7/41 (17.1%) AMG 531-treated patients (p=0.0004). There were no treatment-related serious adverse events and no patients tested positive for neutralizing antibodies against either AMG 531 or endogenous TPO. In summary, as in previous studies, AMG 531 was well-tolerated while effectively increasing and sustaining platelet counts in nonsplenectomized patients with ITP. When compared to placebo, AMG 531 administration resulted in a higher mean platelet count, and was associated with less frequent use of rescue medications.