The US Food and Drug Administration (FDA) has approved eltrombopag (Promacta) for use in patients with severe aplastic anemia (SAA) who have had an insufficient response to immunosuppressive therapy (IST).
Eltrombopag is an oral thrombopoietin receptor agonist that helps to induce the proliferation and differentiation of hematopoietic stem cells to increase blood cell production.
Eltrombopag is already FDA approved to treat patients with chronic immune thrombocytopenia who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.
The drug is also approved to treat thrombocytopenia in patients with chronic hepatitis C to allow for the initiation and maintenance of interferon-based therapy.
The latest FDA approval is based on results from an investigator-sponsored phase 2 study (09-H-0154) conducted by the National Heart, Lung and Blood Institute. Results of this trial were previously published in The New England Journal of Medicine.
Eltrombopag in SAA: Latest trial results
In this study, researchers evaluated eltrombopag in 43 SAA patients who had an insufficient response to at least 1 prior IST and 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 years (range, 17 to 77 years), 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 also had bone marrow aspirates 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.
Eltrombopag is marketed by GlaxoSmithKline under the brand name Promacta in the US and Revolade in most other countries. For more information on eltrombopag, see the prescribing information.
