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Eltrombopag Maintains Platelet Counts During Myelosuppressive Pegylated Interferon Alpha Treatment of Chronic Hepatitis C Virus Infection
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Reported by Jules Levin
DDW, May 19-24, 2007, Washington, DC
G. M. Dusheiko1; J. G. McHutchison2; N. H. Afdhal3; M. L. Shiffman4; M. Rodriguez-Torres5; S. Sigal6; M. Bourliere7; T. Berg8; N. Blackman9; F. M. Campbell10; S. White9
1. Royal Free Hospital, London, United Kingdom.
2. Duke Clinical Research Institute, Durham, NC, USA.
3. Beth Israel Deaconess Medical Center, Boston, MA, USA.
4. Virginia Commonwealth University Health System, Richmond, VA, USA.
5. Fundacion de Investigacion de Diego, San Juan, Puerto Rico.
6. Weill Medical College of Cornell University, New York, NY, USA.
7. Hopital Saint Joseph, Marseille, France.
8. Charite, Berlin, Germany.
9. GlaxoSmithKline, Philadelphia, PA, USA.
10. GlaxoSmithKline, Greenford, United Kingdom.
BACKGROUND AND AIMS
Eltrombopag is an oral, non-peptide, small molecule thrombopoietin receptor (TPO-R) agonist. The safety, efficacy and pharmacokinetics of eltrombopag in HCV-infected subjects with thrombocytopenia precluding initiation of pegylated-interferon (PEG-IFN) and ribavirin have previously been reported. We have now examined the ability of eltrombopag to counteract the myelosuppressive effects of PEG-IFN on platelet counts in HCV-infected patients during treatment. A sub-analysis of data from study TPL102357 was performed to determine if eltrombopag is able to maintain platelet counts in thrombocytopenic subjects during PEG-IFN treatment thus avoiding deleterious dose reductions of PEG-IFN.
METHODS
HCV positive subjects with compensated cirrhosis and platelet counts 20-70,000/uL were randomized (1:1:1:1) to receive 30mg, 50mg, 75mg eltrombopag or placebo once daily for 4 weeks (induction phase). Subjects achieving platelet counts of > 70,000/uL in the induction phase could initiate PEG-IFN/ribavirin therapy along with study drug for 12 weeks (maintenance phase). Platelet count assessments made at the baseline visit were compared to those made at the completion of study drug concomitant with PEG-IFN/ribavirin (Study Day 113).
RESULTS
A total of 74 subjects were enrolled and 49 of those successfully initiated PEG-IFN/ribavirin. Of those subjects who completed the maintenance phase and with available platelet count data for this sub-analysis, 4/7 subjects on 30mg eltrombopag maintained a platelet count above their baseline value at the completion of 12 weeks of PEG-IFN/ribavirin. Similarly, 4/5 and 10/12 subjects on 50mg and 75mg eltrombopag, respectively, maintained a platelet counts above their baseline platelet count at the completion of the maintenance phase. None of the subjects (0/1) on placebo maintained their baseline platelet count while on PEG-IFN. Platelet counts were >50,000/uL for all subjects who had a platelet count above their baseline count at the end of the maintenance phase.
CONCLUSIONS
Eltrombopag was able to maintain platelet counts above the baseline platelet count in thromobocytopenic patients in the presence of 12 weeks of PEG-IFN for the majority of subjects on therapy in study TPL102357. These results support further evaluation of eltrombopag in patients with thrombocytopenia and chronic HCV infection to allow initiation and maintenance of full dose PEG-IFN antiviral therapy.
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