Nplate Increased, Sustained Platelet Counts In Adult Chronic ITP Patients
Amgen Inc. released updated results from the ongoing, open-label extension study of the long-term safety and efficacy of Nplate (romiplostim) in adult patients with chronic immune thrombocytopenic purpura (ITP). Chronic ITP is a chronic and serious autoimmune disorder characterized by lower than expected platelet counts in the blood, sometimes leading to serious bleeding events.
The results were presented today as an oral presentation at the 50th Annual Meeting of the American Society of Hematology (ASH Abstract # 402). Results from a study of Nplate in myelodysplastic syndromes (MDS) also were presented.
"These data show Nplate increased platelet counts in most patients for most of the time, and clinically relevant bleeding was reduced over time," said David J. Kuter, M.D., Chief of Hematology, Massachusetts General Hospital, Boston. "This is significant because Nplate can be a long-term treatment for adult chronic ITP patients, who are at risk of serious bleeding events if their platelet counts drop to less than 30,000 per microliter. These patients have had limited availability to long term treatment options."
These study results showed that overall 74 percent of patients (160/215) achieved a platelet response defined as a platelet count of 50,000 platelets per microliter and doubling of the baseline platelet count (median:17,000 platelets per microliter). A platelet response was achieved by 30 percent (61/207) of patients after the first dose and by 47 percent (94/199) of patients after the third dose. The average treatment period was 76 weeks and the longest duration of treatment was 204 weeks.
Additional key findings from the Extension study show:
-- Platelet counts increased: Platelet counts of Nplate-treated patients were increased from baseline by 20,000 platelets per microliter more than 80 percent of the time in 47 percent of patients and more than half the time in 67 percent of patients.
-- Platelet counts maintained: Platelet count increases of 50,000 platelets per microliter were sustained for greater than or equal to 10, greater than or equal to 25, and greater than or equal to 52 consecutive weeks in 77 percent (127/164), 67 percent (95/141), and 41 percent (48/116) of patients, respectively.
In this study, adverse events (AEs) did not increase with time and were reported in 86 percent of patients, with most mild to moderate in severity. The most common were headache (34 percent), contusion (32 percent), and fatigue (31 percent). Treatment-related and serious AEs were reported in 28 percent and 29 percent of patients, respectively. Treatment-related serious AEs were reported in 7 percent of patients. Five percent of patients (11/215) discontinued treatment due to AEs.
Bone marrow reticulin was present or increased in eight patients with no evidence of progression to collagen fibrosis or chronic idiopathic myelofibrosis. Thrombotic/thromboembolic events were reported in seven patients, of whom six had pre-existing risk factors. To date, one patient developed a neutralizing antibody to Nplate; however, it did not cross react with thrombopoietin and it was absent upon re-testing four months after Nplate treatment was stopped.
This ongoing, open-label study is assessing the safety and efficacy of long-term administration of Nplate in both splenectomized and non-splenectomized adult chronic ITP patients. As of July 2008, 223 patients had enrolled and 215 were treated with Nplate. Sixty-one percent of patients were female and, of the enrolled patients, 44 percent had undergone a splenectomy (removal of the spleen).
Eligible patients had completed a previous ITP Nplate study, with no significant change in medical history. The Nplate starting dose was 1 ug/kg by subcutaneous injection and was adjusted to maintain a platelet count between 50,000 and 200,000 platelets per microliter.
Interim Phase 2 Nplate MDS Data Also Presented (Abstract # 224)
Interim data from an ongoing Phase 2 multicenter, randomized, double-blind, placebo-controlled study evaluating Nplate in patients with low or intermediate risk MDS receiving azacytidine were also presented (n=40). The interim analysis showed that Nplate reduced the incidence of clinically significant, treatment-related thrombocytopenic events and platelet transfusions. Nplate also improved the platelet nadir, defined as the lowest peripheral blood count that occurs secondary to bone marrow suppression, in MDS patients receiving azacytidine.
Each study arm was in combination with azacytidine, and serious AEs were observed in 77 percent of the placebo group, 46 percent of the Nplate 500ug group and 71 percent of the 750ug group. One incident of each of the following events was reported: arthralgia, rash, hypersensitivity, pulmonary hemorrhage, hemorrhage and epistaxis. Two patients in the placebo group died, one of fungal pneumonia and the other of pulmonary hemorrhage. One case of disease progression from MDS to acute myeloid leukemia was observed in the Nplate 500ug treated group.