Long-Term Safety and Efficacy of Oral Eltrombopag for the Treatment of Subjects with Idiopathic Thrombocytopenic Purpura (ITP): Preliminary Data from the EXTEND Study.
Authors: Bussel James B. , Cheng Gregory , Kovaleva Lidia , Saleh Mansoor N. , Meddeb Balkis , Mayer Bhabita , Fraser J. Lee , Aivado Manuel 
Published: October 2019

Idiopathic thrombocytopenic purpura (ITP) is a disease caused by inadequate platelet production as well as increased platelet destruction. Eltrombopag is a first-in-class, oral, non-peptide platelet growth factor that increases platelet counts by interacting with the thrombopoietin receptor on megakaryocytes and their precursors. Accordingly, in two completed 6-week, randomized, double-blind, placebo-controlled studies of adult subjects with chronic ITP, eltrombopag produced a substantial dose-dependent increase in platelet counts. EXTEND is an ongoing, open-label extension study designed to assess the long-term safety and efficacy of oral eltrombopag. Subjects previously enrolled in an eltrombopag study are eligible to enroll in EXTEND after an intervening washout period of at least 4 weeks. Subjects are administered a starting dose of 50 mg/day (which could be increased to 75 mg/day at any time after 3 weeks) in order to reach a platelet count of ≥50,000/uL (stage 1). Then, concomitant ITP medications, if taken at study entry, are tapered to a minimal dose or discontinued entirely (stage 2), whilst maintaining a platelet count of ≥50,000/uL. Eltrombopag is then titrated to a minimal effective dose (25–75 mg/day) required to maintain platelet counts of 50,000/uL-200,000/uL (stage 3). Eltrombopag is continued for as long as the subject continues to benefit (stage 4). Bleeding incidence and severity is assessed using the WHO bleeding scale (Grade 0–4). As of August 6, 2007, data were available on 96 subjects. Ninety-four subjects were administered eltrombopag. Evaluable subjects (n=89) had a median treatment duration of 151 days (2–333 days). At baseline, 42 (44%) subjects had a platelet count ≤15,000/uL, 60 (63%) had evidence of bleeding (WHO Grade 1-4), 44 (46%) were splenectomized, and 35 (36%) were receiving concomitant ITP treatment. Of the sixty-one subjects who entered into the study with a platelet count <30,000/uL, 43 (73%) achieved a platelet count of ≥50,000/uL while on study; 10 of the 61 subjects had at least one count ≥400,000/mL during the study. Of the 94 subjects who received at least one dose of eltrombopag, 78 (83%) reported at least one adverse event; 30 (32%) reported a drug-related adverse event (AE). Most AEs were mild in severity with the most common being headache (20%). Twelve (13%) subjects reported a serious adverse event. Two deaths were reported (traffic accident and hypovolaemic shock), both not related to study medication. To date, these findings of the EXTEND study suggest that eltrombopag is well tolerated and sustains increased platelets counts during long-term treatment.

Stage Description Subjects entering Median Platelet counts (/uL) WHO Grade 2–4 Bleeding n (%) Stage 1 eltrombopag administered 94 16,000 25 (27%) Stage 2 tapering ITP con meds 17 143,500 4 (24%) Stage 3 titrating eltrombpag to maintain platelet counts 46 108,500 3 (7%) Stage 4 treating with eltrombopag long-term 27 104,000 1 (4%)