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Eltrombopag for the treatment of patients with severe aplastic anaemia

The Food and Drug Administration ( FDA ) has approved a supplemental New Drug Application ( sNDA ) for the once-daily use of Eltrombopag in patients with severe aplastic anaemia who have had an insufficient response to immunosuppressive therapy.
Eltrombopag is marketed under the brand name Promacta in the U.S. and Revolade in most ex-U.S. countries.

In addition to the approval of Promacta for severe aplastic anemia in the U.S., Eltrombopag is indicated for the treatment of thrombocytopenia in patients with: chronic immune ( idiopathic ) thrombocytopenia ( ITP ) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.

Eltrombopag gained approval from FDA for severe aplastic anaemia on results from a single-arm, single-centre, open-label phase II study ( 09-H-0154 ).
Eltrombopag was evaluated in 43 patients with severe aplastic anaemia who have had an insufficient response to at least one prior immunosuppressive therapy and who had a platelet count less than or equal to 30 x 109/L.
At baseline, the median platelet count was 20 x 109/L, haemoglobin 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 treated population had a median age of 45 years ( range 17 to 77 years ) and 56% were male. The majority of patients ( 84% ) received at least two prior immunosuppressive therapies.

Eltrombopag was administered at an initial dose of 50 mg once daily for two weeks and increased over two-week periods up to a maximum dose of 150 mg once daily.

The primary endpoint was haematologic response which was initially assessed after 12 weeks of treatment with Eltrombopag. Treatment was discontinued after 16 weeks if no haematologic response was observed.
Additional efficacy assessments included median duration of response in months.

Severe aplastic anaemia ( SAA ) is a very rare but serious blood disorder where the bone marrow fails to make enough red blood cells, white blood cells, and platelets.
The exact cause of the disease is still unknown, but most cases of severe aplastic anaemia are believed to be triggered by an autoimmune reaction where the body attacks blood-forming stem cells located in the bone marrow. As a result, patients with severe aplastic anaemia are at risk for life-threatening infections or bleeding.
In the U.S., approximately 300 to 600 new cases of severe aplastic anaemia are identified each year.

Treatment of severe aplastic anaemia is focused on increasing a patient’s blood cell count; definitive care includes immunosuppressive therapy or hematopoietic stem cell transplantation.
Supportive treatments ( including blood transfusions, platelet transfusions that typically occur once a week, iron chelation therapy, and treatment of infections ) help in the short term to relieve specific symptoms.

Of patients treated with immunosuppressive therapy, one-quarter to one-third will not respond and 30-40% of responders will relapse, causing symptoms to return.
Approximately 40% of severe aplastic anaemia patients who don’t respond to initial immunosuppressive therapy die from infection or bleeding within five years of their diagnosis.

Currently, no established standard of care exists for severe aplastic anaemia patients who have had an insufficient response to immunosuppressive therapy or are ineligible for hematopoietic stem cell transplantation. ( Xagena )

Source: GSK, 2014