Amgen has presented results from the studies on the safety and efficacy of Nplate (Romiplostim) in adult patients with myelodysplastic syndromes (MDS). The results of the studies were presented at the 2009 American Society of Hematology (ASH) annual meeting and exposition.
The ongoing, open-label extension study was designed to evaluate the safety and efficacy of Nplate in lower risk MDS patients. The primary endpoints of the interim study evaluated adverse event rates with long-term use of Nplate and incidence of antibody development to Nplate and/or thrombopoietin (TPO). Secondary endpoints evaluated the incidence of bleeding events and platelet response during the study period.
Nplate was generally well-tolerated, with the majority of patients (n=28) achieving a platelet response (61%) for eight or more consecutive weeks. The primary endpoint evaluating adverse event rates was met, with most patients experiencing mild to moderate with the most common being epistaxis (36%), arthralgia (29%), anemia (21%) and cough (21%). The co-primary endpoint was also met, as no neutralising antibodies to Nplate or TPO were observed, nor progression to acute myeloid leukemia (AML). In addition, no cases of bone marrow fibrosis were reported.
Results for the secondary endpoint showed that 64% of patients (n=18) reported one or more bleeding events and 21% of patients (n=6) reported one or more clinically significant bleeding events. In the study, 29% of patients (n=8) received platelet transfusions. Frequency of bleeding events and platelet transfusions decreased over time.
The data also showed that Nplate was effective with over half (54%) of patients (n=28) achieving a platelet response by week three and 61% achieving a durable platelet response overall (for eight or more consecutive weeks), meeting the additional secondary endpoint. Platelet response was defined as an absolute platelet increase of greater than or equal to 30,000 platelets per microliter for patients starting with less than 20,000 platelets per microliter, or an increase from less than 20,000 platelets per microliter to over 20,000 platelets per microliter and by at least 100%. The study showed that 82% of patients (n=28) had a platelet response and the median platelet response lasted 30 weeks.
Data from two separate Phase 2 studies showed that patients with low and intermediate risk MDS currently receiving either decitabine or lenalidomide showed reduced incidence of clinically thrombocytopenic events and platelet transfusions with the addition of Nplate treatment.
In the study that examined patients with low and intermediate risk MDS receiving decitabine in combination with Nplate, the primary endpoint evaluated the incidence of clinically significant thrombocytopenic events as defined by platelet counts of less than 50,000 platelets per microliter by the third week of treatment, or receipt of platelet transfusions at any time during the study period.
The data showed that the primary endpoint was reached in 79% (n=14) of placebo patients and 80% (n=15) of Nplate patients and after the first cycle of treatment, median platelet counts at the beginning of each decitabine cycle were lower in placebo-treated patients than in Nplate-treated patients. In the last cycle, 30% of placebo treated patients (n=10) and 55% of Nplate treated patients (n=11) had reached median platelet count. In addition, results showed decreased platelet transfusions in Nplate-treated patients compared to placebo (47% vs 57%, respectively).
Secondary endpoints were also met with results showing that treatment was generally well-tolerated in lower-risk MDS patients (all patients in the Nplate and placebo groups experienced at least one adverse event) with improved MDS treatment response after four cycles compared to placebo (47% vs 36%, respectively) and decreased bleeding events (27% vs 43%, respectively) in Nplate-treated patients compared to placebo. Adverse events were mild to moderate with similar treatment-related adverse events between patients taking Nplate and placebo (33% vs 21%, respectively). Similar findings have been reported for use of Nplate in combination with Azacytidine (vidaza).