The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for eltrombopag (Revolade) as a treatment for adults with severe aplastic anemia (SAA) who have had an insufficient response to immunosuppressive therapy (IST) and are not eligible to receive a hematopoietic stem cell transplant (HSCT).
If approved by the European Commission, eltrombopag would be the first treatment option in its class for these patients.
The European Commission will review the CHMP recommendation and is expected to deliver its final decision within 3 months. The decision will be applicable to all 28 European Union member states plus Iceland, Norway, and Liechtenstein.
Phase 2 trial of eltrombopag in SAA
The CHMP’s positive opinion of eltrombopag is mainly based on results of a phase 2 trial (NCT00922883). Results from this ongoing study were published in NEJM in 2012 and Blood in 2013.
The trial has enrolled 43 patients with SAA who had an insufficient response to at least one prior IST and who had a platelet count of 30 x 109/L or less.
At baseline, the median platelet count was 20 x 109/L, hemoglobin was 8.4 g/dL, the absolute neutrophil count was 0.58 x 109/L, and absolute reticulocyte count was 24.3 x 109/L.
Patients had a median age of 45 (range, 17 to 77), and 56% were male. The majority of patients (84%) received at least 2 prior ISTs.
Patients received eltrombopag at an initial dose of 50 mg once daily for 2 weeks. The dose increased over 2-week periods to a maximum of 150 mg once daily.
The study’s primary endpoint was hematologic response, which was initially assessed after 12 weeks of treatment. Treatment was discontinued after 16 weeks in patients who did not exhibit a hematologic response.
Forty percent of patients (n=17) experienced a hematologic response in at least one lineage—platelets, red blood cells (RBCs), or white blood cells—after week 12.
In the extension phase of the study, 8 patients achieved a multilineage response. Four of these patients subsequently tapered off treatment and maintained the response. The median follow up was 8.1 months (range, 7.2 to 10.6 months).
Ninety-one percent of patients were platelet-transfusion-dependent at baseline. Patients who responded to eltrombopag did not require platelet transfusions for a median of 200 days (range, 8 to 1096 days).
Eighty-six percent of patients were RBC-transfusion-dependent at baseline. Patients who responded to eltrombopag did not require RBC transfusions for a median of 208 days (range, 15 to 1082 days).
The most common adverse events (≥20%) associated with eltrombopag were nausea (33%), fatigue (28%), cough (23%), diarrhea (21%), and headache (21%).
Patients were also evaluated for cytogenetic abnormalities. Eight patients had a new cytogenetic abnormality after treatment, including 5 patients who had complex changes in chromosome 7.
Patients who develop new cytogenetic abnormalities while on eltrombopag may need to be taken off treatment.
About eltrombopag
Eltrombopag is already approved to treat SAA in the US and Canada. The drug recently gained approval in the US to treat children age 6 and older who have chronic immune thrombocytopenia and have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.
Eltrombopag is approved in more than 100 countries to treat adults with chronic immune thrombocytopenia who have had an inadequate response to or are intolerant of other treatments. The drug is approved in more than 45 countries for the treatment of thrombocytopenia in patients with chronic hepatitis C to allow them to initiate and maintain interferon-based therapy.
Eltrombopag is marketed under the brand name Promacta in the US and Revolade in most other countries. For more details on the drug, see the European Medicines Agency’s Summary of Product Characteristics.
