Amgen Inc. said its investigational, platelet-increasing therapy romiplostim (AMG 531) met its primary end point in a pivotal phase III study in adult patients with chronic Immune Thrombocytopenic Purpura (ITP).
The randomised study was conducted in 63 patients who had their spleens removed (splenectomized) after other failed treatments.
Adult ITP is a chronic and serious disorder caused by a deregulated immune system that mistakenly destroys the body's own platelets and impairs platelet production, which results in low platelet counts. Platelets are specialized blood cells that help prevent and stop bleeding by participating in clotting. The risk of bleeding events increases as platelet counts decrease, especially as they go below 30,000 platelets per microliter.
Additionally, romiplostim-treated patients taking concurrent ITP medications such as corticosteroids were able to reduce or discontinue these medications. Adult ITP is a serious chronic autoimmune disorder characterized by low platelet counts in the blood, a condition known as thrombocytopenia.
"The majority of available therapies for ITP decrease platelet destruction by the immune system, but we have been aware for some time that inadequate platelet production is also a problem in this disorder. Romiplostim is an investigational therapy that stimulates platelet production in a manner similar to the body's natural hormone thrombopoietin, and is currently being evaluated for it's ability to increase the platelet count by increasing platelet production in ITP," said Dr Terry Gernsheimer, associate professor of medicine, Division of Hematology, University of Washington School of Medicine, and the Puget Sound Blood Center. "The encouraging results of this study highlight the potential of this new therapeutic approach to the treatment of adult patients with chronic ITP."
Amgen has recently filed for regulatory approval of romiplostim for use in the treatment of thrombocytopenia in adults with chronic ITP in the United States (US), European Union (EU), Australia and Canada. Regulatory authorities in Australia and Canada have granted priority review of Amgen's application.
This phase III study met its primary endpoint with 38.1 per cent of romiplostim-treated patients achieving durable platelet response compared to none of the patients receiving placebo. Durable platelet response was defined as a weekly platelet count of greater than or equal to 50,000 platelets per microliter for greater than six of the final eight study weeks. Additionally, no rescue medications (defined as any additional ITP medicine needed to increase platelet counts) were administered at any time during the study to patients achieving durable platelet response.
Overall platelet response was 78.6 per cent in romiplostim-treated patients compared to no response in the placebo group. Overall platelet response was defined as either transient platelet response (greater than or equal to four weekly platelet responses, separated by greater than 8 weeks from administration of any rescue medication) or durable platelet response. The mean number of weeks with a platelet response was significantly greater in romiplostim-treated patients than in the placebo group (12.3 weeks vs. 0.2 week, p less than 0.0001).
Two serious treatment-related adverse events were reported in the romiplostim group. In one patient, elevated bone marrow reticulin that returned to baseline three months after withdrawal of romiplostim was reported. Another patient experienced thrombosis that was successfully treated, allowing study continuation. The most commonly reported adverse events in the romiplostim group included myalgia, dizziness, pharyngolaryngeal pain, pyrexia, arthralgia, insomnia, and diarrhea. Serious bleeding adverse events (greater than or equal to Grade 3) were reported in patients in both the romiplostim groups, all occurring at platelet counts below 30,000 per microliter. No patient developed neutralizing antibodies against either romiplostim or endogenous TPO.
The randomised, double-blind, placebo controlled, phase III study assessed the efficacy and safety of romiplostim in splenectomized adults with chronic ITP. Sixty-three splenectomized patients were enrolled (placebo, 21; romiplostim, 42) with a median age of 51 years (range 26-88) and a mean baseline platelet count of 13,500 platelets per microliter. These patients continued to have low platelet counts after a median of 7.75 years of having chronic ITP and more than five prior ITP treatments, including splenectomy. The romiplostim starting dose was 1 ug/kg by subcutaneous injection and was adjusted based on weekly platelet response.
Romiplostim is an investigational thrombopoiesis-stimulating Fc-peptide fusion protein ("peptibody") that contains two component regions. Peptibodies are engineered therapeutic molecules that can bind to human drug targets and contain peptides linked to the constant domains of antibodies. Romiplostim works similarly to thrombopoietin (TPO), a natural protein in the body.
Romiplostim stimulates the TPO receptor, which is necessary for growth and maturation of bone marrow cells and plays a very important role in platelet sustaining platelet counts. In 2004, the US Food and Drug Administration (FDA) granted fast track designation for romiplostim. Romiplostim has received orphan designation for this proposed indication in four major global regions, including the US. (2003); the EU and Switzerland (2005); and Japan (2006).