Pivotal Phase 3 Romiplostim Study in Splenectomized Patients Meets Primary Endpoints
Data Show Romiplostim Increased and Sustained Platelet Counts in Splenectomized Adult Patients with Immune Thrombocytopenic Purpura
ATLANTA -- Dec. 8, 2007--Amgen today announced results from a randomized, pivotal Phase 3 study that showed romiplostim (AMG 531) increased and sustained platelet counts in splenectomized (spleen removed) adult patients with chronic Immune Thrombocytopenic Purpura (ITP). 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. These Phase 3 data will be presented in a Plenary Session at the American Society of Hematology (ASH) 49th Annual Meeting in Atlanta, GA (Abstract #2).
"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."
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.
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 (U.S.), European Union (EU), Australia and Canada. Regulatory authorities in Australia and Canada have granted priority review of Amgen's application.
Efficacy and safety data from another pivotal Phase 3 study evaluating romiplostim in non-splenectomized chronic ITP patients as well as interim results from a long-term extension study in chronic adult ITP will be presented on Monday, Dec. 10, 2007 (Abstracts #565 and 568).
This Phase 3 study met its primary endpoint with 38.1 percent of romiplostim-treated patients (n=42) achieving durable platelet response compared to none of the patients receiving placebo (n=21, p=0.0013). 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 percent in romiplostim-treated patients compared to no response in the placebo group (p less than 0.0001). 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).
Romiplostim-treated patients receiving concurrent ITP medications (n=12/12) discontinued or reduced use of such medications compared to 16.7 percent of placebo-treated patients (n=1/6). Across the study, 26.2 percent of romiplostim-treated patients required rescue medications compared to 57.1 percent of those in the placebo group (p=0.0175).
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 (n=4/42, 9.5 percent) and placebo (n=4/21, 19 percent) groups, all occurring at platelet counts below 30,000 per microliter. No patient developed neutralizing antibodies against either romiplostim or endogenous TPO.
About the Phase 3 Study
This randomized, double-blind, placebo controlled, Phase 3 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 U.S. 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 U.S. (2003); the EU and Switzerland (2005); and Japan (2006).
About Adult ITP
Adult Immune (idiopathic) thrombocytopenic purpura (ITP) is a chronic and serious autoimmune disorder characterized by low levels of platelets in the blood, a condition known as thrombocytopenia. A normal platelet range for a person without ITP is 150,000 - 400,000 platelets per microliter of blood. The risk of a bleeding event increases when platelet counts drop to less than 30,000 platelets per microliter.
With ITP, platelets are destroyed by the patient's own immune system. ITP has historically been considered a disease of platelet destruction; however, recent data also suggest that the body's natural platelet production processes are unable to compensate for low levels of platelets in the blood. Increasing the rate of platelet production may address low platelet levels associated with ITP.
According to the Platelet Disorder Support Association, approximately 200,000 Americans have been diagnosed with ITP. Additionally, U.S. and Europe combined, ITP is estimated to affect 50 to 100 new persons per million annually.
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