FDA Approves Eltrombopag for Severe Aplastic Anemia

Paolo Paoletti, MD

The FDA has approved eltrombopag (Promacta) as a treatment for patients with severe aplastic anemia (SAA) following an insufficient response to immunosuppressive therapy, based on data from an open-label, single-arm phase II trial.

The approval was based on findings from a phase II study conducted by the National Institutes of Health that demonstrated a robust normalization of blood cell counts in patients with SAA who received treatment with eltrombopag. The small molecule thrombopoietin receptor agonist eltrombopag received a breakthrough therapy designation from the FDA for the treatment of cytopenias in patients with severe aplastic anemia (SAA) who have had insufficient response to immunosuppressive therapy in February 2014.

“FDA approval of Promacta addresses a significant treatment need for this very rare but serious blood disorder in those who have failed current treatment options,” Paolo Paoletti, MD, the president of Oncology, at GlaxoSmithKline, the company developing the drug, said in a press release. “Through collaboration with the National Institutes of Health, whose studies demonstrate the potential for Promacta to achieve a hematologic response in at least one lineage — red blood cells, platelets, or white blood cells – patients now have a treatment option where one didn’t previously exist.”

In the phase II study, 43 patients with SAA who had a platelet count ≤30 x 109/L and who experienced an insufficient reponse to immunosuppressive therapy received treatment with eltrombopag. Overall, 84% of patients in the study had received at least two prior immunosuppressive therapies.

Eltrombopag was administered at a starting dose of 50-mg daily, which was increased in 2-week increments to a maximum dose of 150 mg daily. Responding patients continued to receive the drug in an expansion trial. At baseline, the median platelet count was 20 x 109/L, hemoglobin was 8.4 g/dL, absolute neutrophil count (ANC) was 0.58 x 109/L, and absolute reticulocyte count was 24.3 x 109/L. The primary endpoint of the study was hematologic response at 12 weeks, which was defined as a 20,000/µl increase in blood cell counts above baseline.

In the study, 40% experienced a hematologic response, including tri- and bilineage responses. A total of 17 patients continued treatment in the extension phase, with 8 achieving a response across several parameters. Half of the patients in the extension cohort tapered off therapy while maintaining a response.

Patients remained platelet transfusion-free for a median of 200 days with eltrombopag. Additionally, patients were red blood cell transfusion-free for a median of 208 days. Five patients had blood counts near normal ranges at a median of 28.5 months.

The most common adverse reactions were nausea (33%), fatigue (28%), cough (23%), diarrhea (21%), and headache (21%). Of the 43 patients enrolled, 8 had a new cytogenetic abnormality reported, including five patients who had complex changes in chromosome 7, suggesting the need to monitor bone marrow aspirates for cytogenetic changes in patients on eltrombopag. However, no patients had evolved to acute myeloid leukemia at the time of the analysis.

Eltrombopag was initially approved in 2008 for the treatment of thrombocytopenia in patients with idiopathic thrombocytopenic purpura who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.