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

AMG 531 is a novel thrombopoiesis-stimulating peptibody that acts by stimulating the thrombopoietin (TPO) receptor. We report efficacy data in splenectomized 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-three splenectomized patients were enrolled (placebo, 21; AMG 531, 42), with a median age of 52 years (range 26 to 88) and a mean baseline platelet count 14.7x10⁹/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. 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. Sixteen of the 42 splenectomized patients (38.1%) receiving AMG 531 achieved a durable platelet response compared to 0/21 (0.0%) receiving placebo (p=0.0013). Overall response, defined as either durable or transient platelet response (≥4 weekly platelet responses), was observed in 33/42 (78.6%) patients receiving AMG 531, compared to 0/21 (0%) placebo patients. The mean number of weekly platelet responses (platelet count ≥50x10⁹/L) was significantly greater in patients receiving AMG 531 (12.3/24 weeks, 51%) compared to placebo (0.2/24 weeks, 1%) (p<0.0001). AMG 531 reduced the proportion of patients requiring ITP rescue medications, defined as either increase from baseline in dose of concurrent medication or use of new medication to increase platelet counts. Twelve of 21 (57.1%) placebo-treated patients received rescue medications compared to just 11/42 (26.2%) AMG 531-treated patients (p=0.0175). In addition, 12/12 (100.0%) AMG 531-treated patients compared to 1/6 (16.7%) placebo-treated patients either discontinued or reduced by >25% their concurrent ITP medications. AMG 531 was well-tolerated. There were 2 treatment-related serious adverse events; 1 patient with elevated bone marrow reticulin that returned to baseline 3 months after withdrawal of AMG 531, and 1 patient experienced thrombosis that was successfully treated allowing study continuation. No patient developed neutralizing antibodies against either AMG 531 or endogenous TPO. In summary, AMG 531 was well-tolerated, and effectively increased and sustained platelet counts in splenectomized patients with ITP. AMG 531-treated patients required less frequent rescue medications in comparison to those receiving placebo, and were able to reduce their use of concurrent therapies.