GSK receives marketing authorisation from the European Commission for additional Revolade™ (eltrombopag) indication

GlaxoSmithKline plc announced today that the European Commission has granted an additional indication for Revolade™ (eltrombopag) as a treatment for low platelet counts (thrombocytopenia) in adult patients with chronic hepatitis C infection, where the degree of thrombocytopenia is the main factor preventing the initiation or limiting the ability to maintain optimal interferon (IFN)-based therapy.¹

Thrombocytopenia (platelet count ≤150Gi/L) can occur in people with chronic hepatitis C infection as a consequence of liver damage.2 It is also a common side effect of peginterferon (pIFN)-based therapy.^3,4

25 percent of patients with chronic hepatitis C have thrombocytopenia5 and up to nine percent of patients are severely thrombocytopenic (platelet count <50Gi/L).⁶

Thrombocytopenia may prevent the initiation5 and maintenance of pIFN-based treatment, thereby reducing a patient’s chances of achieving a sustained virologic response (SVR)^*7 – the primary goal of hepatitis C treatment.

“Until now, prescribers were without an option for treating low platelet counts in patients with chronic hepatitis C infection” said Paolo Paoletti, President, GlaxoSmithKline Oncology. “Today’s announcement is important as it means that healthcare professionals can now use Revolade to help patients start and stay on interferon therapy which will facilitate achieving the best outcome for these individuals – that being a sustained virologic response.”

The ENABLE clinical trials

The marketing authorisation granted to eltrombopag is based on results from ENABLE-1 and -2 (Eltrombopag to INitiate and Maintain Interferon Antiviral Treatment to Benefit Subjects with Hepatitis C related Liver DiseasE), two Phase III global, multicentre, two-part studies (n=1,520), that comprised an open-label pre-antiviral treatment phase and a randomised, double-blind, placebo-controlled antiviral treatment phase. Eighty percent of the patients had bridging fibrosis or cirrhosis.^1,8 ENABLE-1 utilised peginterferon alfa-2a plus ribavirin for antiviral treatment and ENABLE-2 utilised peginterferon alfa-2b plus ribavirin.¹

Efficacy

Phase III clinical studies demonstrated that eltrombopag may achieve and maintain target platelet counts in chronic hepatitis C patients with associated thrombocytopenia.8,9

* where the hepatitis C virus remains undetectable for six months – following completion of antiviral therapy

Eltrombopag enabled 95 percent of patients with chronic hepatitis C-associated thrombocytopenia to achieve platelet counts sufficient for initiation of pIFN-based therapy.^1,8-10

§ Eltrombopag enabled more patients to maintain pIFN-based therapy without dose reduction compared to placebo (45 percent vs 27 percent).¹

§ Eltrombopag enabled approximately one in five patients who, because of thrombocytopenia, were previously ineligible or poor candidates for pIFN-based therapy to achieve SVR.^1,8,9

Safety

The Phase III clinical studies showed an increased risk of adverse events, including potentially fatal hepatic decompensation and thromboembolic events, in thrombocytopenic hepatitis C patients with advanced chronic liver disease, as defined by low albumin levels ≤ 35 g/L or MELD (model for end-stage liver disease) score ≥ 10, when treated with eltrombopag in combination with IFN-based therapy.¹

§ Eltrombopag may cause hepatotoxicity. Eltrombopag in combination with IFN and ribavirin, in patients with chronic hepatitis C infection, may increase the risk of hepatic decompensation.¹

§ An increase in platelet counts with eltrombopag may heighten the risk of thrombotic/thromboembolic complications.¹

§ Serious adverse events were more common in patients treated with eltrombopag.^11,12

References

1. REVOLADE^TM Summary of Product Characteristics.
2. Violi F et al. Hepatol 2011;55:1415-1427.
3. Pegasys Summary of Product Characteristics March 2013.
4. Pegintron Summary of Product Characteristics May 2012.
5. Giannini EG et al. Liver Int 2012;32(6):1113-1119.
6. Behnava B et al. Hep Mon 2006;6(2):67-69.
7. Everson GT et al. Hepatol 2006;44:1675-1684.
8. Dusheiko G et al. Poster session presented at: The 47^th Annual Meeting of the European Association for the Study of the Liver [EASL].  Barcelona, Spain. Apr 18-12 2012.
9. Afdhal N et al. Poster session presented at: The 62^nd Annual Meeting of the American Association for the Study of Liver Diseases [AASLD]. San Francisco, CA, USA. Nov 4-8 2011.
10. Giannini EG et al. Expert Opin Pharmacother 2013;14(5):669-678.
11. ENABLE-1 Clinical Trials. Identifier TPL108390. Accessed January 2013.
12. ENABLE-2 Clinical Trials. Identifier TPL108390. Accessed January 2013.