Pivotal Phase 3 Nplate Study in Non-Splenectomized Patients Met Primary EndpointsATLANTA--(BUSINESS WIRE)--Dec 10, 2007 - Amgen Inc. (NASDAQ:AMGN) today announced results from a second randomized, pivotal Phase 3 study where Nplate(TM) (romiplostim) increased and sustained platelet counts in non-splenectomized (spleen not removed) adult patients with chronic Immune Thrombocytopenic Purpura (ITP). Additionally, Nplate-treated patients taking concurrent ITP medications such as corticosteroids were able to reduce or discontinue these medications. Adult ITP is a chronic and serious autoimmune disorder characterized by low platelet counts in the blood, a condition known as thrombocytopenia. These Phase 3 data were presented today in an oral session at the 49th American Society of Hematology Annual Meeting (ASH) in Atlanta, Georgia (Abstract #565).
"Patients without a splenectomy, or for whom this surgical procedure is not an option, often require treatment with corticosteroids or immunoglobulin therapy," said David J. Kuter, M.D., D. Phil., Chief of Hematology, Massachusetts General Hospital, Boston. "This six month study is encouraging in that most Nplate-treated patients were able to decrease or stop such treatment."
Additional data presented today in an oral session included updated interim results from an ongoing, open-label extension study evaluating extended treatment (up to 122 weeks of patient follow-up) with Nplate on platelet counts in adult patients with chronic ITP (Abstract #568).
Efficacy and safety data from another pivotal Phase 3 study evaluating Nplate in splenectomized chronic adult ITP patients were presented yesterday in a Plenary Session (Abstract #2).
Nplate works similarly to thrombopoietin (TPO), a natural protein in the body. The active peptide component stimulates the TPO receptor, which is necessary for growth and maturation of bone marrow cells and plays a central role in increasing platelet counts.
Randomized Phase 3 Study of Nplate in Non-Splenectomized Patients (Abstract #565)
This Phase 3 study met its primary endpoint with 61 percent of Nplate-treated patients (n=41) achieving durable platelet response compared to 4.8 percent of patients receiving placebo (n=21). 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 in the study patients achieving a durable response (p less than 0.0001).
Overall response was 87.8 percent in Nplate-treated patients as compared to 14.3 percent of patients 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 rescue therapy) or durable platelet response. The mean number of weeks with a platelet response was significantly greater in Nplate-treated patients than in the placebo group (15.2 weeks vs. 1.3 weeks). Across the study, 17.1 percent of the Nplate-treated patients required rescue medications compared to 61.9 percent of placebo-treated patients (p=0.0004).
Five serious adverse events were reported, none of which were deemed treatment-related. The most commonly reported adverse events in the Nplate group included myalgia, dizziness, pharyngolaryngeal pain, pyrexia, arthralgia, insomnia, and diarrhea. No patients tested positive for neutralizing antibodies against either Nplate or endogenous TPO protein.
The randomized, double-blind, placebo-controlled Phase 3 study was designed to evaluate the efficacy and safety of Nplate to increase and sustain platelet counts in adult patients with chronic ITP. The Nplate starting dose was 1 ug/kg by subcutaneous injection and was adjusted based on weekly platelet response.
Amgen has filed for regulatory approval of Nplate 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 the U.S., Australia and Canada have granted priority review of Amgen's application.
Nplate Extension-Study (Abstract #568)
An updated interim analysis from an ongoing, open-label extension study (n=136 patients) showed that the majority (range 50-75 percent) of Nplate-treated patients achieved long-term platelet response. Response was defined as a weekly platelet count of greater than or equal to 50,000 platelets per microliter, and doubling of the baseline platelet count. The longest treatment duration was greater than 120 weeks (n=2), and the shortest treatment duration was greater than 24 weeks (n=89). At the time of analysis, 20 patients had been followed for 96 weeks or longer. Of the 30 patients on concurrent corticosteroids at study entry, 63 percent were able to discontinue or reduce their corticosteroid treatment through the course of the trial. The use of rescue medications was decreased from 24 percent during weeks 1-12 of study to 6 percent during weeks 109-120 of the study.
"Currently, Nplate is the only thrombopoietic ITP treatment for which there are over two years of follow-up data," said James Bussel, M.D., director of Platelet Research, Weill Medical College, Cornell University, New York. "This latest interim analysis is promising for the potential of Nplate as a treatment for adult patients with chronic ITP."
In this study, Nplate appeared generally well-tolerated and adverse events did not increase in frequency during the course of the trial. The five most frequently reported adverse events were headache (31 percent), contusion (27 percent), fatigue (24 percent), diarrhea (24 percent) and epistaxis (23 percent). Eleven patients experienced serious treatment-related adverse events, of which three patients were withdrawn from the study due to vaginal hemorrhage, reversible increased bone marrow reticulin (reported as myelofibrosis), and monoclonal gammopathy of undetermined significance (MGUS), initially reported as multiple myeloma). To date, one patient developed a neutralizing antibody to Nplate; however, it was absent upon re-testing four months after Nplate treatment was stopped.
This ongoing, open-label extension study is assessing the safety and efficacy of long-term administration of Nplate in both non-splenectomized and splenectomized adult chronic ITP patients. Eligible patients had completed a previous ITP Nplate study, and had a baseline platelet count of less than 50,000 platelets per microliter, with no significant change in medical history. The Nplate starting dose was 1 ug/kg by subcutaneous injection and was adjusted based on weekly platelet response. Patients were administered Nplate by injection once weekly unless their platelet count exceeded 400,000 platelets per microliter. Concurrent corticosteroid treatment could be tapered when patients' platelet counts were above 50,000 platelets per microliter.
About Nplate (Romiplostim)
Nplate 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. Nplate works similarly to thrombopoietin (TPO), a natural protein in the body. Nplate stimulates the TPO receptor, which is necessary for growth and maturation of bone marrow cells and plays a very important role in increasing platelet counts. In 2004, the U.S. Food and Drug Administration (FDA) granted fast track designation for Nplate. Orphan designation for ITP was granted in 2003 by the FDA and in 2005 by the European Agency for the Evaluation of Medicinal Products (EMEA). Nplate has received orphan designation for this proposed indication in four major global regions, including the U.S. (2003); EU and Switzerland (2005); and Japan (2006).
About Adult ITP
Adult Immune (idiopathic) thrombocytopenic purpura (ITP) is a chronic and potentially serious autoimmune disorder characterized by low platelet counts 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 platelet counts in the blood. Increasing the rate of platelet production may address low platelet counts associated with ITP.
Amgen discovers, develops and delivers innovative human therapeutics. A biotechnology pioneer since 1980, Amgen was one of the first companies to realize the new science's promise by bringing safe and effective medicines from lab, to manufacturing plant, to patient. Amgen therapeutics have changed the practice of medicine, helping millions of people around the world in the fight against cancer, kidney disease, rheumatoid arthritis, and other serious illnesses. With a deep and broad pipeline of potential new medicines, Amgen remains committed to advancing science to dramatically improve people's lives. To learn more about our pioneering science and our vital medicines, visit www.amgen.com.
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Posted: December 2007