Interim results from an international, single-arm study (“209 study”) evaluating the safety and efficacy of romiplostim (Nplate?, Amgen) in adults with primary immune thrombocytopenia (ITP) – a rare blood disorder – demonstrated that the investigational drug induced a rapid platelet response with a good safety profile in adult ITP patients with low platelet counts and bleeding symptoms.
“This is the largest ever study in adult ITP with over 400 patients enrolled. These interim data highlight again Nplate’s ability to treat adult patients successfully, including those with varying severity of the condition,” said Ann Janssens M.D., Department of Hematology, University Hospitals Leuven, Belgium. “Nplate has consistently demonstrated that it can significantly increase and maintain platelet counts in adult ITP patients, highlighting its importance as a well-tolerated treatment option.”
These data were presented today at the 16th Congress of the European Hematology Association (EHA) in London (Abstract #0223).
In patients with ITP, platelets – blood elements needed to prevent bleeding – are destroyed by the patient’s own immune system. Recent data also suggest that low platelet counts in the blood may be caused by the inability of the body’s natural processes to produce platelets. Low platelet counts leave adult ITP patients open to sudden serious bleeding events. The risk for serious bleeding events increases when platelet counts drop to less than 30,000 platelets per microliter; normal counts range from 150,000 to 400,000 platelets per microliter. ITP has historically been considered a disease of platelet destruction although recent data suggest that the body’s natural platelet production processes in ITP 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. Adult chronic ITP has an incidence of 5.8-6.6 per 100,000 in the United States and an estimated 2.0 per 100,000 in the European Union.[2,3]
Trial Results
Interim results from the first 235 patients show that romiplostim was able to induce a platelet response in a large majority of adult patients (90%) with primary ITP treated with romiplostim for up to 201 weeks. The median time to response was one week and over the course of the study, a doubling of the platelet count to greater than or equal to 50,000 platelets per microliter was achieved by 86% of patients who received the trial drug. A further platelet count increase of greater than or equal to 20,000 platelets per microliter from baseline was achieved by 91% of patients who received romiplostim.
Adverse events
Incidence and type of adverse events (AEs) in patients treated with romiplostim were consistent with those reported in previous studies. The most common side effects were mild and included headache (28% of patients), fatigue (23%) and arthralgia (19%). No neutralizing antibodies to romiplostim or thrombopoietin (TPO) or hematopoieitic malignancies or MDS events were reported.
Study design
The trial was designed as an open-label, single-arm study of romiplostim for the treatment of adults with primary ITP. Romiplostim was administered once weekly, with dose adjustments to maintain platelet counts of greater than or equal to 50,000 platelets per microliter. The primary study objective was incidence of AEs and antibody formation. Secondary study objectives were to evaluate platelet responses defined as either [1] doubling of baseline count and a platelet count greater than or equal to 50,000 platelets per microliter or [2] a platelet count increase of greater than or equal 20,000 platelets per microliter from baseline.[1] As of June 2009, 235 patients had been treated for a median of 18 weeks with a maximum duration of 201 weeks. Sixty percent of patients had previously undergone splenectomy.
References
[1] Data on file with Amgen. Interim Results from an International Multi-center, Single-arm Study Evaluating the Safety and Efficacy of Romiplostim in Adults with Primary Immune Thrombocytopenia (ITP). Abstract# 0223
[2] McMillan R. Therapy for Adults with Refractory Chronic Immune Thrombocytopenic Purpura. Ann Intern Med 1997;126:307-314
[3] Fogarty PF et al. Curr Opin Hematol 2007;14:515-519.
