Clinical data
The safety and efficacy of romiplostim have been eva luated for up to 3 years of continuous treatment. In clinical studies, treatment with romiplostim resulted in dose-dependent increases in platelet count. Time to reach the maximum effect on platelet count is approximately 10-14 days, and is independent of the dose. After a single subcutaneous dose of 1 to 10 µg/kg romiplostim in ITP patients, the peak platelet count was 1.3 to 14.9 times greater than the baseline platelet count over a 2 to 3 week period and the response was variable among patients. The platelet counts of ITP patients who received 6 weekly doses of 1 or 3 µg/kg of romiplostim were within the range of 50 to 450 x 109/l for most patients. Of the 271 patients who received romiplostim in ITP clinical studies, 55 (20%) were age 65 and over, and 27 (10%) were 75 and over. No overall differences in safety or efficacy have been observed between older and younger patients in the placebo-controlled studies.
Results from pivotal placebo-controlled studies
The safety and efficacy of romiplostim was eva luated in two placebo-controlled, double-blind studies in adults with ITP who had completed at least one treatment prior to study entry and are representative of the entire spectrum of such ITP patients.
Study S1 (212) eva luated patients who were non-splenectomised and had an inadequate response or were intolerant to prior therapies. Patients had been diagnosed with ITP for approximately 2 years at the time of study entry. Patients had a median of 3 (range, 1 to 7) treatments for ITP prior to study entry. Prior treatments included corticosteroids (90% of all patients), immunoglobulins (76%), rituximab (29%), cytotoxic therapies (21%), danazol (11%), and azathioprine (5%). Patients had a median platelet count of 19 x 109/l at study entry.
Study S2 (105) eva luated patients who were splenectomised and continued to have thrombocytopenia. Patients had been diagnosed with ITP for approximately 8 years at the time of study entry. In addition to a splenectomy, patients had a median of 6 (range, 3 to 10) treatments for ITP prior to study entry. Prior treatments included corticosteroids (98% of all patients), immunoglobulins (97%), rituximab (71%), danazol (37%), cytotoxic therapies (68%), and azathioprine (24%). Patients had a median platelet count of 14 x 109/l at study entry.
Both studies were similarly designed. Patients ( 18 years) were randomised in a 2:1 ratio to receive a starting dose of romiplostim 1 µg/kg or placebo. Patients received single subcutaneous weekly injections for 24 weeks. Doses were adjusted to maintain (50 to 200 x 109/l) platelet counts. In both studies, efficacy was determined by an increase in the proportion of patients who achieved a durable platelet response. The median average weekly dose for splenectomised patients was 3 µg/kg and for non-splenectomised patients was 2 µg/kg.
A significantly higher proportion of patients receiving romiplostim achieved a durable platelet response compared to patients receiving placebo in both studies. Following the first 4-weeks of study romiplostim maintained platelet counts 50 x 109/l in between 50% to 70% of patients during the 6 month treatment period in the placebo-controlled studies. In the placebo group, 0% to 7% of patients were able achieve a platelet count response during the 6 months of treatment. A summary of the key efficacy endpoints is presented below.
Summary of key efficacy results from placebo-c |
