The European Commission has approved Novartis' Revolade (eltrombopag) for the treatment of adults with severe aplastic anemia (SAA) who were either refractory to prior immunosuppressive therapy or heavily pretreated and are unsuitable for hematopoietic stem cell transplant.
"Today's approval from the European Commission is important news for adults in the EU with severe aplastic anemia, who now have an alternative to standard therapies that have not provided sufficient benefit," said Alessandro Riva, MD, global head, Novartis Oncology Development and Medical Affairs.
"Revolade helps address an unmet need in this community and underscores our commitment to patients affected by rare diseases."
SAA is a blood disorder where the bone marrow does not make enough red blood cells, white blood cells and platelets. Two out of every one million people in Europe are diagnosed with aplastic anemia per year, a portion of which are severe cases. The exact cause of the disease is still unknown, but most cases of SAA 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 SAA are at risk for life-threatening infections or bleeding.
Treatment of SAA is focused on increasing the number of healthy cells in the blood (blood cell count). The current standard of care includes IST or hematopoietic stem cell transplantation. Of patients treated with IST, one-quarter to one-third will not respond and 30-40 per cent of responders will relapse, causing symptoms to return. Approximately 40 per cent of SAA patients who don't respond to initial IST die from infection or bleeding within five years of their diagnosis.
The approval is based on the results of a pivotal open-label phase II study (ELT112523) and two supporting phase II studies (ELT116826 and ELT116643) conducted by the National Heart, Lung and Blood Institute (NHLBI) at the National Institutes of Health (NIH). The pivotal study demonstrated a hematologic response (40 per cent) in SAA patients treated with Revolade who had an insufficient response to IST. The most common adverse reactions (>=20 per cent) in the pivotal single-arm study of 43 patients were nausea, fatigue, cough, transaminase increased, diarrhea, and headache.
The European Commission approval applies to all 28 EU member states plus Iceland, Norway and Liechtenstein. In August of 2014, eltrombopag (marketed as Promacta in the USA), was approved by the US Food and Drug Administration for once-daily use in patients with SAA who have had an insufficient response to IST. Eltrombopag is also approved for SAA in Canada.
In the single-arm, single-center, open-label phase II study (NCT00922883 (link is external)), eltrombopag was evaluated in 43 patients with SAA who have had an insufficient response to at least one prior IST and who had a platelet count <=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 per cent were male. The majority of patients (84 per cent) 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.
Revolade is approved in more than 100 countries worldwide for the treatment of thrombocytopenia in adult patients with chronic immune (idiopathic) thrombocytopenic purpura (ITP) who have had an inadequate response or are intolerant to other treatments, and in over 45 countries worldwide for the treatment of thrombocytopenia (low blood platelet counts) in patients with chronic hepatitis C to allow them to initiate and maintain interferon-based therapy. Eltrombopag (marketed as Promacta in the USA), is approved by the US Food and Drug Administration for once-daily use in patients with SAA who have had an insufficient response to IST and was also recently approved for the treatment of children one year and older with chronic ITP who have had an insufficient response to corticosteroids, immunoglobulins or splenectomy.