For Health Care Professionals Outside the US

Studies of REVOLADE
In Immune Thrombocytopenia (ITP)

Study TRA100773A1

A phase 2, randomised, double-blind, placebo-controlled trial.

  • Enrolled 117 adults with previously treated ITP and baseline platelet count <30 x 109/L
  • Patients were randomised in a 1:1:1:1 ratio to receive a fixed dose of 30, 50, or 75 mg of REVOLADE once daily or placebo for up to 6 weeks
    • Concomitant immunosuppressive treatment (primarily glucocorticoids) was permitted if the dose had been stable for at least 1 month and remained stable throughout the study
    • Other ITP treatments must have been completed at least 2 weeks before study enrolment
  • The primary efficacy end point was a shift from baseline platelet count of <30 x 109/L to ≥50 x 109/L at Week 6
    • This was achieved by 70% of patients treated with REVOLADE 50 mg once daily vs 11% with placebo
Review efficacy data from study TRA100773A

EXTEND1,2

An open-label extension study of REVOLADE.

  • Objectives included evaluating the long-term safety and efficacy of REVOLADE
  • Enrolled 302 adults with ITP who had completed a previous REVOLADE study
  • Data shown are for up to 8.8 years (457 weeks) of continuous treatment with REVOLADE
Review efficacy data from the EXTEND study
Review safety data from the EXTEND study

RAISE3

A phase 3, randomised, double-blind, placebo-controlled trial.

  • Enrolled 197 adults with previously treated ITP and baseline platelet count <30 x 109/L
  • Patients received local standard of care plus either REVOLADE 50 mg once daily or placebo for 6 months
    • Dose modifications were based on individual platelet response, to a maximum of 75 mg once daily and a minimum of 25 mg once daily
  • Primary end point was the odds of response (defined as a platelet count of ≥50 x 109/L and ≤400 x 109/L) during treatment
    • This was achieved by 79% of patients treated with REVOLADE vs 28% with placebo
Review efficacy data from the RAISE study
Review safety data from the RAISE study

REPEAT4

An open-label, single-arm study that evaluated the efficacy and safety of repeated short courses of REVOLADE for up to 3 cycles of treatment.

  • Enrolled 66 adults with chronic ITP who had a baseline platelet count between 20 x 109/L and 50 x 109/L
  • At enrolment, patients had ITP for more than 6 months and had been previously treated with ≥1 ITP therapy including (but not limited to) corticosteroids, immunoglobulins, azathioprine, danazol, ciclophosphamide, and/or rituximab
  • Primary end point was consistency of response, defined as proportion of patients who responded in Cycle 1 who also responded in Cycle 2 or 3
    • Response was defined as a platelet count ≥50 x 109/L and at least twice the baseline (Day 1) platelet count for that cycle after up to 42 days of treatment
Review efficacy data from the REPEAT study

PETIT1,5,6

A 7-week, phase 2, double-blind, placebo-controlled trial to assess the efficacy, safety, and dosing of REVOLADE.

  • Enrolled 67 children ≥1 year of age with relapsed or refractory chronic ITP
  • Patients were randomised 2:1 to treatment with REVOLADE (n=45) or placebo (n=22)
    • Concomitant use of stable maintenance ITP therapy—including (but not limited to) corticosteroids, azathioprine, danazol, ciclosporin A, and mycophenolate mofetil—was permitted
  • At baseline:
    • 51% of patients had platelet counts ≤15 x 109/L
    • 84% of REVOLADE-treated and 86% of placebo-treated patients had received ≥2 prior ITP therapies
    • 5 patients in the REVOLADE group had had a prior splenectomy
  • Primary end point was proportion of patients who achieved platelet count ≥50 x 109/L at least once between Weeks 1 and 6 in the randomised, double-blind period of the study in the absence of rescue therapy
    • The double-blind phase was followed by a dose-finding phase in which patients received open-label treatment with REVOLADE for up to 24 weeks
Review efficacy data from the PETIT study
Review safety data from the PETIT study

PETIT 21,5,7

A 13-week, phase 3, double-blind, placebo-controlled trial to assess the efficacy and safety of REVOLADE.

  • Enrolled 92 children ≥1 year of age with relapsed or refractory chronic ITP
  • Patients were randomised 2:1 to treatment with REVOLADE (n=63) or placebo (n=29)
    • Concomitant use of stable maintenance ITP therapy—including (but not limited to) corticosteroids, azathioprine, danazol, ciclosporin A, and mycophenolate mofetil—was permitted
  • At baseline:
    • 62% of patients had platelet counts ≤15 x 109/L
    • 73% of REVOLADE-treated and 90% of placebo-treated patients had received ≥2 prior ITP therapies
    • 4 patients in the REVOLADE group had had a prior splenectomy
  • Primary end point was proportion of patients who achieved platelet count ≥50 x 109/L for ≥6 weeks of the 8 weeks between Weeks 5 and 12 in the randomised, double-blind period of the study in the absence of rescue therapy
    • The double-blind phase was followed by open-label treatment with REVOLADE for up to 24 weeks
Review efficacy data from the PETIT 2 study
Review safety data from the PETIT 2 study

Study of REVOLADE
In Severe Aplastic Anaemia (SAA)

Relapsed/refractory study1,5,8,9

A prospective, open-label, nonrandomised, single-arm, investigator-sponsored, dose-modification study conducted by the NIH in the United States to assess the safety and efficacy of REVOLADE.

  • Enrolled 43 patients ≥12 years of age with SAA and immunosuppressive therapy–refractory thrombocytopenia
  • Patients had a median age of 45 years, had an insufficient response to ≥1 prior immunosuppressive therapy, or were relapsed/refractory and had responded to ≥1 prior cycle of immunosuppressive therapy, but were refractory to the most recent course of immunosuppressive therapy
  • Primary end point was haematologic response—assessed after 12 weeks of treatment—defined as meeting one or more of the following criteria:
    • Platelet count increases to 20 x 109/L above baseline or stable platelet counts with transfusion independence for a minimum of 8 weeks
    • Haemoglobin (HgB) increase ≥1.5 g/dL for patients with pretreatment HgB <9 g/dL or a reduction of ≥4 units of red blood cell transfusions for 8 consecutive weeks
    • Absolute neutrophil count increase of 100% or an increase by >0.5 x 109/L
  • Patients who responded could continue therapy in an extension phase
Review efficacy data from this study in SAA
Review safety data from this study in SAA

Studies of REVOLADE in Chronic
Hepatitis C Virus–Associated Thrombocytopenia

ENABLE-1 and ENABLE-210

Two international randomised, double-blind, placebo-controlled studies.

  • Enrolled adults with thrombocytopenia associated with hepatitis C virus (HCV) infection and had baseline platelet count <75 x 109/L

Each study had a similar 2-phase design.

    • In the open-label phase 1 (initiation phase):
      • Patients (N=1,520) were treated with once-daily REVOLADE in escalating doses of 25 mg, 50 mg, 75 mg, or 100 mg, depending on platelet response
      • Assigned treatment continued for between 2 to 9 weeks
      • Patients were entered into phase 2 after they reached the predefined minimum threshold for initiating antiviral therapy
        • In ENABLE-1, this threshold was 90 x 109/L
        • In ENABLE-1, this threshold was 100 x 109/L
    • In the double-blinded phase 2:
      • Patients (n=1,441) were randomised 2:1 to either REVOLADE or placebo
        • Treatment continued for either 24 weeks or 48 weeks, depending on the patient’s HCV genotype
      • Patients also received antiviral therapy
        • In ENABLE-1, patients received subcutaneous peginterferon-2a 180 µg weekly + oral ribavirin
        • In ENABLE-2, patients received subcutaneous peginterferon-2b 1.5 µg/kg weekly + oral ribavirin
    • Primary end point was percentage of patients who achieved sustained virologic response, defined as the percentage of patients with no detectable HCV-RNA 24 weeks after completing phase 2
Review efficacy data from the ENABLE-1 and ENABLE-2 studies
Review safety data from the ENABLE-1 and ENABLE-2 studies
References: 1. Data on file. 2. Wong RSM, Saleh MN, Khelif A, et al. Safety and efficacy of long-term treatment of chronic/persistent ITP with eltrombopag: final results of the EXTEND study. Blood. 2017;130(3):2527-2536. 3. Cheng G, Saleh MN, Marcher C, et al. Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study. Lancet. 2011;377(9763):393-402. 4. Bussel JB, Saleh MN, Vasey SY, Mayer B, Arning M, Stone NL. Repeated short-term use of eltrombopag in patients with chronic immune thrombocytopenia (ITP). Br J Haematol. 2013;160(4):538-546. 5. REVOLADE Summary of Product Characteristics. February 2019. 6. Bussel JB, de Miguel PG, Despotovic JD, et al. Eltrombopag for the treatment of children with persistent and chronic immune thrombocytopenia (PETIT): a randomised, multicentre, placebo-controlled study. Lancet Haematol. 2015;2(8):e315-e325. 7. Grainger JD, Locatelli F, Chotsampancharoen T, et al. Eltrombopag for children with chronic immune thrombocytopenia (PETIT2): a randomised, multicentre, placebo-controlled trial. Lancet. 2015;386(10004):1649-1658. 8. REVOLADE Core Data Sheet. Version 2.4. 17 June 2019. 9. Desmond R, Townsley DM, Dumitriu B, et al. Eltrombopag restores trilineage hematopoiesis in refractory severe aplastic anemia that can be sustained on discontinuation of drug. Blood. 2014;123(12):1818-1825. 10. Afdhal NH, Dusheiko GM, Giannini EG, et al. Eltrombopag increases platelet numbers in thrombocytopenic patients with HCV infection and cirrhosis, allowing for effective antiviral therapy. Gastroenterology. 2014;146(2):442-452.
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