Abstract

Chronic ITP is characterized by increased platelet destruction and suboptimal platelet production. Romiplostim is an investigational Fc-peptide fusion protein (peptibody) being studied for its ability to increase platelet counts in patients with chronic ITP. We report data from an open-label extension study of romiplostim in adult patients with chronic ITP. Collection of safety and efficacy data from long-term treatment of these patients is ongoing. Eligible patients had completed a prior romiplostim study and had platelet counts □50×109/L. Romiplostim was administered subcutaneously once weekly with dose adjustments to maintain a platelet count of 50–250×109/L. As of July 13 2007, 142 patients had been treated with romiplostim. Their median time since diagnosis was 6.4 years (range 0.6–46.4 years). Most were female (67%) and had previously undergone a splenectomy (60%). The median baseline platelet count was 17×109/L (range 1–50×109/L). The median duration of treatment was 65 weeks (range 1–156 weeks). Twenty-nine (20%) patients discontinued the study, 10 (7%) due to adverse events (AEs) [2 each of bone marrow reticulin and thrombosis; 1 each of bleeding, pain, cardiac arrest, pneumonia, hepatic and renal failure, and monoclonal gammopathy of undetermined significance]. Different measures of platelet count response were analyzed; any platelet counts within 8 weeks of receiving rescue medications were excluded from these analyses. Platelet counts were increased from baseline by ≥20×109/L more than 80% of the time in 54% of patients and more than 50% of the time in 73% of patients. Platelet counts remained above 20×109/L more than 90% of the time in 67% of patients and more than 50% of the time in 94% of patients. A platelet count >50×109/L and double baseline was achieved by 30% (42/138) of patients after the first dose, by 51% (71/138) of patients after the third dose, and by 87% (124/142) of patients overall. The durability of platelet count increases was analyzed: platelet counts >50×109/L were sustained for ≥10, ≥25, and ≥52 consecutive weeks in 78% (102/131), 54% (66/122), and 35% (29/84) of patients, respectively. The patient incidence of bleeding events both of any severity and of clinical significance (≥Grade 3) declined over time (Table). AEs were reported in 95% of patients, with most mild to moderate in severity. The most common were headache (37%); nasopharyngitis (32%); and contusion, fatigue and epistaxis (each 30%). AE frequency did not increase with time on study (Table). Bone marrow reticulin was present or increased in 8 patients with no evidence of progression to collagen fibrosis or chronic idiopathic myelofibrosis. Thrombotic events were reported in 7 (5%) patients; 6 had pre-existing risk factors for thrombosis. In conclusion, romiplostim increased platelet counts in most patients for most of the time, and clinically relevant bleeding was reduced over time. Romiplostim was well-tolerated and AEs did not increase with longer duration of treatment.

Table. Summary of patient incidence of AEs by study period

 <24 wks (N=142) n (%) 24 to <48 wks (N=126) n (%) 48 to <72 wks (N=97) n (%) 72 to <96 wks (N=65) n (%) 96 to <120 wks (N=29) n (%) 120 to <144 wks (N=25) n (%) 
AEs 129 (91) 110 (87) 64 (66) 36 (55) 23 (79) 21 (84) 
Serious AEs 25 (18) 13 (10) 7 (7) 4 (6) 4 (14) 1 (4) 
Treatment-related AEs 48 (34) 14 (11) 12 (12) 7 (11) 4 (14) 3 (12) 
Treatment-related serious AEs 6 (4) 3 (2) 1 (1) 2 (3) 1 (3) 1 (4) 
Study withdrawals due to AEs 4 (3) 5 (4) 0 (0) 0 (0) 0 (0) 1 (4) 
Bleeding any grade 60 (42) 37 (29) 22 (23) 13 (20) 11 (38) 8 (32) 
Bleeding ≥ Grade 2 (moderate) 25 (18) 12 (10) 8 (8) 4 (6) 3 (10) 2 (8) 
Bleeding ≥ Grade 3 difference in thisresponsebetween refractory (severe) 9 (6) 1 (1) 1 (1) 1 (2) 0 (0) 0 (0) 
 <24 wks (N=142) n (%) 24 to <48 wks (N=126) n (%) 48 to <72 wks (N=97) n (%) 72 to <96 wks (N=65) n (%) 96 to <120 wks (N=29) n (%) 120 to <144 wks (N=25) n (%) 
AEs 129 (91) 110 (87) 64 (66) 36 (55) 23 (79) 21 (84) 
Serious AEs 25 (18) 13 (10) 7 (7) 4 (6) 4 (14) 1 (4) 
Treatment-related AEs 48 (34) 14 (11) 12 (12) 7 (11) 4 (14) 3 (12) 
Treatment-related serious AEs 6 (4) 3 (2) 1 (1) 2 (3) 1 (3) 1 (4) 
Study withdrawals due to AEs 4 (3) 5 (4) 0 (0) 0 (0) 0 (0) 1 (4) 
Bleeding any grade 60 (42) 37 (29) 22 (23) 13 (20) 11 (38) 8 (32) 
Bleeding ≥ Grade 2 (moderate) 25 (18) 12 (10) 8 (8) 4 (6) 3 (10) 2 (8) 
Bleeding ≥ Grade 3 difference in thisresponsebetween refractory (severe) 9 (6) 1 (1) 1 (1) 1 (2) 0 (0) 0 (0) 

Disclosures: Kuter:Amgen Inc.: Consultancy, Research Funding; GlaxoSmithKline: Consultancy, Research Funding; Ligand: Consultancy, Research Funding; MGI Pharma: Consultancy, Research Funding. Bussel:Amgen Inc.: Equity Ownership, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Baxter: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Biogen-IDEC: Research Funding; Cangene: Research Funding; Genentech: Research Funding; Genzyme: Research Funding; GlaxoSmithKline: Equity Ownership, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Immunomedics: Research Funding; Ligand: Membership on an entity’s Board of Directors or advisory committees, Research Funding; MGI Pharma/Eisai, Inc.: Research Funding; Sysmex: Research Funding. Newland:Amgen Inc.: Honoraria, Research Funding; Baxter: Research Funding; Celgene: Research Funding; GlaxoSmithKline: Honoraria, Research Funding; Pangenetics: Membership on an entity’s Board of Directors or advisory committees. Wasser:Amgen Inc.: Research Funding, Speakers Bureau. Gehl:Amgen Inc.: Employment. Nie:Amgen Inc.: Employment. Berger:Amgen Inc.: Employment.

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