ライフサイエンスコーパス: eltrombopag

1 median of 13 months (range, 1-15 months) off eltrombopag.

2 atients with a response continued to receive eltrombopag.

3 to LPDs to assess the safety and efficacy of eltrombopag.

4 and MYH9 genes, who had previously received Eltrombopag.

5 functional megakaryocytes that responded to Eltrombopag.

6 ted with the Thrombopoietin-receptor agonist Eltrombopag.

7 s, resulting in the early discontinuation of eltrombopag.

8 1-2 study of immunosuppressive therapy plus eltrombopag.

9 to splenectomy, rituximab, romiplostim, and eltrombopag.

10 tions such as S505N and W515K, as well as by eltrombopag.

11 atient assigned to receive placebo was given eltrombopag.

12 LT patients whose platelet count improved on eltrombopag.

13 all patients could receive up to 24 weeks of eltrombopag.

14 ceiving placebo, 10 of 14 receiving 30 mg of eltrombopag, 14 of 19 receiving 50 mg of eltrombopag, an

15 atment, with 45 patients assigned to receive eltrombopag (16 children aged 12-17 years, 19 aged 6-11

16 us infusion on days 1-7 [100 mg/m(2)]), with eltrombopag 200 mg (100 mg for east Asians) or placebo o

17 ar proportions had MDS (50 [51%] patients to eltrombopag, 22 (47%) patients to placebo) or AML (48 [4

18 Proportionately fewer patients who received eltrombopag (23 [37%] of 63 patients) had WHO grades 1-4

19 nts to placebo) or AML (48 [49%] patients to eltrombopag, 25 [53%] patients to placebo).

20 millimeter were randomly assigned to receive eltrombopag (30, 50, or 75 mg daily) or placebo daily fo

21 ive the oral thrombopoietin-receptor agonist eltrombopag (30, 50, or 75 mg daily) or placebo.

22 tment received standard care plus once-daily eltrombopag 50 mg (n=76) or placebo (n=38) for up to 6 w

23 were randomly assigned to receive oral daily eltrombopag 50 mg from 21 days preoperatively to postope

24 cacy, safety, and tolerability of once daily eltrombopag 50 mg, and explored the efficacy of a dose i

25 ents were randomly assigned (2:1) to receive eltrombopag (50 mg to 300 mg) or placebo for at least 24

26 0 mg by mouth, days 1-4) in combination with eltrombopag (50 mg, days 5-32) in 12 adults with newly d

27 rom weeks 5-12 were significantly lower with eltrombopag (54% [95% CI 43-64]) than with placebo (69%

28 avoided in 104 of 145 patients who received eltrombopag (72%) and in 28 of 147 who received placebo

29 tinib initiation was 4 (IQR, 2-5), including eltrombopag (76.1%), romiplostim (57.2%), and IV immunog

30 Eltrombopag, a synthetic small molecule mimetic of TPO t

31 ia that was refractory to immunosuppression, eltrombopag, a synthetic thrombopoietin-receptor agonist

32 All 5 patients with a platelet response to Eltrombopag, a thrombopoietic agent, but none responding

33 We asked whether eltrombopag, a thrombopoietic agent, would increase plat

34 nd colleagues examine the in vivo effects of eltrombopag, a thrombopoietin receptor agonist (TPO-RA),

35 We tested whether eltrombopag, a thrombopoietin receptor agonist, might be

36 The effects of eltrombopag, a thrombopoietin-receptor agonist, on plate

37 hat were suspected to be study drug-related (eltrombopag: acute kidney injury, arterial thrombosis, b

38 Orally available, TPO nonpeptide mimetics (eltrombopag, AKR-501) bind and activate the TPO receptor

39 Here, we show that Eltrombopag, an FDA-approved drug, is a direct inhibitor

40 Eltrombopag, an FDA-approved non-peptidyl thrombopoietin

41 In this study (ASPIRE), we aimed to assess eltrombopag, an oral thrombopoietin receptor agonist, fo

42 Eltrombopag, an oral thrombopoietin receptor agonist, in

43 Eltrombopag, an oral thrombopoietin receptor agonist, st

44 In part 1, 17 patients received eltrombopag and 11 patients completed treatment; four ex

45 21 (33%) patients receiving eltrombopag and 16 (47%) patients receiving placebo died

46 eved for 30 (79%) of 38 patients assigned to eltrombopag and 22 (61%) of 36 patients assigned to intr

47 63 patients were assigned to receive eltrombopag and 29 were assigned to receive placebo.

48 whom 74 (80%) were randomly assigned: 38 to eltrombopag and 36 to intravenous immunoglobulin.

49 is shared between the small-molecule agonist eltrombopag and canonical and novel activating TpoR muta

50 occurred in five (8%) patients who received eltrombopag and four (14%) who received placebo.

51 ts occurred in five (11%) patients receiving eltrombopag and four (19%) patients receiving placebo, a

52 sessment of long-term safety and efficacy of eltrombopag and its effect on survival (phase 2 part of

53 her was reported in ten (16%) patients given eltrombopag and nine (26%) patients given placebo.

54 No significant difference between the eltrombopag and placebo groups was observed in bleeding

55 of other adverse events were similar in the eltrombopag and placebo groups.

56 se progression occurred in 17% (for both) of eltrombopag and placebo patients with no difference in s

57 TION: No new safety concerns were noted with eltrombopag and the trial met the primary objective of a

58 adverse events (four [9%] patients receiving eltrombopag and two (10%) patients receiving placebo) we

59 No deaths in patients receiving eltrombopag and two deaths in patients receiving placebo

60 of eltrombopag, 14 of 19 receiving 50 mg of eltrombopag, and 21 of 23 receiving 75 mg of eltrombopag

61 During part 1, patients received eltrombopag, and dose-escalation criteria for part 2 wer

62 mbopag, in 15 of 19 (79%) receiving 50 mg of eltrombopag, and in 20 of 21 (95%) receiving 75 mg of el

63 After 3 months, 82.5% and 74.3% of eltrombopag- and romiplostim-treated patients, respectiv

64 Platelet responses to romiplostim and eltrombopag are seen in a much greater percentage than i

65 Two agents, romiplostim and eltrombopag, are now licensed and their place in the tre

66 lacebo (13 [42%] of 31 patients) than in the eltrombopag arm (eight [14%] of 59 patients; p=0.0025).

67 score >= 2) occurred less frequently in the eltrombopag arm than in the placebo group (incidence rat

68 horse ATG plus cyclosporine with or without eltrombopag as front-line therapy in previously untreate

69 tem were observed in 6 patients who received eltrombopag, as compared with 1 who received placebo, re

70 ding phase, patients aged 6-17 years started eltrombopag at 25 mg once per day (12.5 mg for those wei

71 Twenty-five patients received eltrombopag at a dose of 50 mg, which could be increased

72 atment period in which all patients received eltrombopag at either the starting dose (if they were fo

73 than 50,000 per cubic millimeter to receive eltrombopag, at a dose of 75 mg daily, or placebo for 14

74 Eltrombopag belongs to a new class of thrombopoietin-mim

75 Eltrombopag binds the BAX trigger site distinctly from B

76 Here, we report that eltrombopag bound to the TET2 catalytic domain and inhib

77 let reactivity to TRAP only in responders to eltrombopag but not to levels above those in controls; w

78 25 (40%) patients who received eltrombopag compared with one (3%) patient who received

79 Response to eltrombopag compared with placebo was not affected by pr

80 weeks 1 to 6, 28 (62%) patients who received eltrombopag, compared with seven (32%) who received plac

81 Our results showed that eltrombopag could be used to increase platelet counts an

82 han 80% of patients receiving 50 or 75 mg of eltrombopag daily had an increased platelet count.

83 In conclusion, eltrombopag/dexamethasone is a feasible frontline therap

84 baseline platelet activation than controls, eltrombopag did not cause platelet activation or hyper-r

85 However, two patients assigned to receive eltrombopag did not receive the study drug and one was l

86 Eltrombopag dose adjustments were allowed weekly based o

87 Eltrombopag doses up to 300 mg daily had an acceptable s

88 Eltrombopag (ELT) is a thrombopoietin receptor agonist r

89 t unexpectedly restored a normal response to eltrombopag (ELT), but not to TPO.

90 Eltrombopag (EP) is a small-molecule, nonpeptide thrombo

91 Eltrombopag (EPAG) received approval from the US Food an

92 d hematologic responses with the addition of eltrombopag (EPAG) to standard IST for SAA when compared

93 Her anemia remitted on eltrombopag (EPAG), but surprisingly, mosaicism was unch

94 m analysis of the ongoing open-label EXTEND (Eltrombopag eXTENded Dosing) study evaluates the safety

95 ed to investigate the safety and efficacy of eltrombopag for children with chronic immune thrombocyto

96 This study evaluated the efficacy of eltrombopag for increasing platelet counts and reducing

97 alized, pre-treatment response prediction to Eltrombopag for individual patients.

98 med to assess the safety and tolerability of eltrombopag for the treatment of thrombocytopenia in adu

99 preclinical rationale for further testing of Eltrombopag for treatment of thrombocytopenia in AML and

100 f the eltrombopag regimen (cohort 1 received eltrombopag from day 14 to 6 months, cohort 2 from day 1

101 ations were done in 40 (63%) patients in the eltrombopag group and 17 (50%) patients in the placebo g

102 achieved for 29 (78%) of 37 patients in the eltrombopag group and 20 (63%) of 32 in the intravenous

103 63 (98%) patients in the eltrombopag group and 32 (94%) patients in the placebo g

104 73 patients in the eltrombopag group and 37 in the placebo group were inclu

105 er were reported in six (9%) patients in the eltrombopag group and four (12%) patients in the placebo

106 adverse events were fatigue (six [6%] in the eltrombopag group and one [2%] in the placebo group), hy

107 events occurred in 24 (32%) patients in the eltrombopag group compared with 14 (20%) patients in the

108 39 (53%) patients in the eltrombopag group died versus 29 (41%) patients in the p

109 ccurred in seven (12%) of 59 patients in the eltrombopag group versus five (16%) of 31 patients in th

110 s occurred in 27 (46%) of 59 patients in the eltrombopag group versus nine events in five (16%) of 31

111 s occurred in 28 (47%) of 59 patients in the eltrombopag group versus one (3%) of 31 patients in the

112 d in mean (SD) age (56.7 years [12.3] in the eltrombopag group vs 56.6 years [11.6] in the placebo gr

113 cause of adverse events: two patients in the eltrombopag group withdrew because of increased liver am

114 Two serious adverse events occurred in the eltrombopag group: one treatment-related pulmonary embol

115 patients) or immunosuppressive therapy plus eltrombopag (Group B, 96 patients).

116 In the eltrombopag groups receiving 30, 50, and 75 mg per day,

117 verse events were similar in the placebo and eltrombopag groups.

118 Patients receiving eltrombopag had less bleeding at any time during the stu

119 The thrombopoietin receptor agonist eltrombopag has been shown to be safe, tolerable, and ef

120 t production in WAS/XLT is less than in ITP, eltrombopag has beneficial effects on platelet count but

121 We have previously demonstrated that eltrombopag has efficacy in this setting with 44% (11/25

122 Eltrombopag has shown promising results in the treatment

123 thrombopoietic agents including AMG 531 and eltrombopag have shown promise in the treatment of throm

124 Some of the eltrombopag hematopoietic activity has been attributed t

125 Among responders to eltrombopag, immature platelet fraction in 3 WAS/XLT pat

126 single-group, phase 1-2 study indicated that eltrombopag improved the efficacy of standard immunosupp

127 ) study evaluates the safety and efficacy of eltrombopag in 299 patients treated up to 3 years.

128 y evaluated long-term safety and efficacy of eltrombopag in adults with ITP who had completed a previ

129 The majority of patients who remained on eltrombopag in an extension study (14/17) continued to s

130 ed to investigate the efficacy and safety of eltrombopag in children with persistent or chronic immun

131 art long-term efficacy and safety results of eltrombopag in patients with low-risk MDS and severe thr

132 ined standard immunosuppressive therapy with eltrombopag in previously untreated patients with severe

133 th alemtuzumab or the thrombopoietin mimetic eltrombopag in refractory AA.

134 aused two (3%) of 65 patients to discontinue eltrombopag in the open-label phase.

135 The role of eltrombopag in these patients warrants further investiga

136 placebo, in 9 of 12 (75%) receiving 30 mg of eltrombopag, in 15 of 19 (79%) receiving 50 mg of eltrom

137 , developed new cytogenetic abnormalities on eltrombopag, including 5 with chromosome 7 loss or parti

138 rombopag were dose dependent and linear, and eltrombopag increased platelet counts in a dose-dependen

139 Eltrombopag increased platelet counts in a dose-dependen

140 Eltrombopag increases and maintains hemostatic platelet

141 microthrombocytopenia; and (2) although the eltrombopag-induced increase in platelet production in W

142 Eltrombopag is a new, orally active thrombopoietin-recep

143 These observations indicate that eltrombopag is a once-daily, oral TpoR agonist with demo

144 Eltrombopag is a small molecule thrombopoietin receptor

145 Eltrombopag is a TPO nonpeptide mimetic administered ora

146 Eltrombopag is active and well tolerated in ITP secondar

147 Eltrombopag is an effective alternative to intravenous i

148 Eltrombopag is an effective treatment for managment of t

149 Eltrombopag is an oral thrombopoietin-receptor agonist.

150 Eltrombopag is an oral, non-peptide, thrombopoietin-rece

151 The oral thrombopoietin receptor agonist eltrombopag is approved for treatment of adults with chr

152 Accordingly, Eltrombopag is capable of inhibiting BAX-mediated apopto

153 Eltrombopag is efficacious in a subset of patients with

154 INTERPRETATION: Eltrombopag is well-tolerated in patients with lower-ris

155 Eltrombopag led to a slight increase in platelet reactiv

156 AMG 531 and eltrombopag markedly increase platelet counts in patient

157 e primary objective of a reduction in CRTEs; eltrombopag might be a treatment option for thrombocytop

158 However, treatment with eltrombopag might increase risk of thrombosis.

159 ed, 169 patients were randomly assigned oral eltrombopag (N = 112) or placebo (N = 57) at a starting

160 = 17; neonates, n = 18) treated with either eltrombopag (n = 8) or romiplostim (n = 7) during pregna

161 domly assigned 98 patients to receive either eltrombopag (n=64) or placebo (n=34).

162 d 148 were then randomly assigned to receive eltrombopag (n=74) and placebo (n=74).

163 145 patients to receive supportive care plus eltrombopag (n=98) or placebo (n=47); similar proportion

164 Eltrombopag neither led to increased 5-bromo-2-deoxyurid

165 In this work, we studied the effects of Eltrombopag on proliferation, apoptosis, differentiation

166 (block size of three), to receive once-daily eltrombopag or matching placebo dose adjusted from 50 mg

167 ed supportive standard of care and initiated eltrombopag or placebo at 100 mg per day (50 mg per day

168 ould then be initiated, with continuation of eltrombopag or placebo for 12 additional weeks.

169 nd randomly assigned (2:1) to receive either eltrombopag or placebo tablets (or oral suspension formu

170 let (PLT) count (<30 x 10(3)/mm(3)) received eltrombopag or placebo until disease progression.

171 of eltrombopag) while the administration of eltrombopag or placebo was continued.

172 sing an interactive voice-response system to eltrombopag or placebo, stratified by baseline platelet

173 ntiviral therapy, with concurrent receipt of eltrombopag or placebo, were completed by 36%, 53%, and

174 er L were randomly assigned (2:1) to receive eltrombopag or placebo.

175 ag, and in 20 of 21 (95%) receiving 75 mg of eltrombopag (P<0.001).

176 43 (59%) eltrombopag patients and six (16%) placebo patients resp

177 s (AEs) was observed, a higher proportion of eltrombopag patients experienced grade 3-4 AEs (chi(2) =

178 w-up (IQR, 14-68) occurred in 47/111 (42.3%) eltrombopag patients versus 6/54 (11.1%) in placebo (odd

179 In eltrombopag patients, 12/47 (25.5%) lost the PLT-R, with

180 nts were randomly assigned in a 2:1 ratio of eltrombopag:placebo by a validated randomisation system.

181 mine whether the oral thrombopoietin mimetic eltrombopag (Promacta) can improve blood counts.

182 sed clonogenic capacity at concentrations of Eltrombopag ranging from 0.1 to 30 microg/mL.

183 Patients who were allocated eltrombopag received tablets (except for those aged 1-5

184 Two eltrombopag recipients (arterial thrombosis n=1; myocard

185 Seven eltrombopag recipients and two placebo recipients had se

186 Eltrombopag reduced the need for platelet transfusions i

187 timing of initiation and the duration of the eltrombopag regimen (cohort 1 received eltrombopag from

188 atients receiving 30 mg, 50 mg, and 75 mg of eltrombopag, respectively, and by 6% of patients in the

189 Thrombopoietin receptor agonists (eltrombopag; romiplostim) seem to improve hemostasis, bu

190 Eltrombopag (SB-497 115) is a first-in-class, oral, smal

191 adults with ITP who had completed a previous eltrombopag study.

192 fficacy analysis who increased their dose of eltrombopag, ten (29%) responded.

193 se events that occurred more frequently with eltrombopag than with placebo included nasopharyngitis (

194 of BAX inhibition and reveal a mechanism for Eltrombopag that may expand its use in diseases of uncon

195 Eltrombopag therapy increases platelet counts in patient

196 rse events leading to study discontinuation (eltrombopag, three [4%]; placebo, two [5%]), were simila

197 The addition of eltrombopag to immunosuppressive therapy was associated

198 The addition of eltrombopag to standard immunosuppressive therapy improv

199 ous adverse events were reported in 56 (58%) eltrombopag-treated patients and 32 (68%) placebo-treate

200 e platelet function in 20 patients receiving eltrombopag treatment at days 0, 7, and 28.

201 Eltrombopag treatment expanded TET2-proficient normal he

202 In phase 2/3 trials, eltrombopag treatment of 6 months or less in patients wi

203 Eltrombopag treatment resulted in an increased platelet

204 Eltrombopag treatment results in a durable trilineage he

205 n response to high-dose ADP was lower during eltrombopag treatment than at baseline.

206 he 302 patients enrolled, median duration of eltrombopag treatment was 2.37 years (2 days-8.76 years)

207 Before eltrombopag treatment with no ex vivo agonist, platelet

208 ithout added agonist was unchanged following eltrombopag treatment, whereas a slight increase in P-se

209 f grade 3-4 adverse events during treatment (eltrombopag, two [3%]; placebo, one [3%]) and adverse ev

210 is study investigated safety and efficacy of eltrombopag versus placebo during anthracycline-based in

211 g were headache (13 [30%] patients receiving eltrombopag vs nine [43%] patients receiving placebo), u

212 Responses were similar in all cohorts (eltrombopag vs placebo: 39% vs 10% for patients aged 12-

213 re similar (three [5%] patients who received eltrombopag vs two [7%] patients who received placebo).

214 Median exposure to eltrombopag was 16 months; median dose at week 4 was 50

215 clinical trial in 73 healthy male subjects, eltrombopag was administered as once-daily oral capsules

216 Treatment with eltrombopag was associated with multilineage clinical re

217 Furthermore, we found that Eltrombopag was capable of increasing megakaryocytic dif

218 Eltrombopag was effective and relatively safe in low-ris

219 EXTEND demonstrated that long-term use of eltrombopag was effective in maintaining platelet counts

220 Long-term treatment with eltrombopag was generally safe, well tolerated, and effe

221 Eltrombopag was initiated at 50 mg/day, with a maximum o

222 We aimed to establish whether perioperative eltrombopag was non-inferior to intravenous immunoglobul

223 or the groups receiving 30, 50, and 75 mg of eltrombopag were 26,000, 128,000, and 183,000 per cubic

224 The pharmacokinetics of eltrombopag were dose dependent and linear, and eltrombo

225 The most common adverse events with eltrombopag were headache (13 [30%] patients receiving e

226 ractory symptomatic ITP and 3 were receiving eltrombopag when pregnancy started.

227 Eltrombopag, which produced a sustained platelet respons

228 eltrombopag, and 21 of 23 receiving 75 mg of eltrombopag) while the administration of eltrombopag or

229 ata from this trial do not support combining eltrombopag with induction chemotherapy in patients with