The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion for Novartis' Revolade (eltrombopag) for the treatment of adult patients with severe aplastic anaemia (SAA) who have had an insufficient response to immunosuppressive therapy (IST) and are not eligible to receive a hematopoietic stem cell transplant.

"Today's CHMP opinion marks a key milestone towards Revolade becoming the first approved therapy in its class in the European Union for patients with severe aplastic anaemia who have not responded to or are ineligible for existing treatments," said Alessandro Riva, MD, global head, Novartis oncology development and medical affairs.

"Our commitment to oncology includes continuing to work towards new treatments for patients impacted by rare diseases like SAA, especially when limited options exist."

SAA is a blood disorder where the bone marrow fails to make enough red blood cells, white blood cells and platelets. Two out of every one million people in Europe and North America are diagnosed with aplastic anaemia 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 a patient's 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 CHMP positive opinion 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 (33 per cent), fatigue (28 per cent), cough (23 per cent), diarrhoea (21 per cent), and headache (21 per cent).

The European Commission will review the CHMP recommendation and is expected to deliver its final decision within three months. The decision will be applicable 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), 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, 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 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 hematologic response, which was initially assessed after 12 weeks of treatment with eltrombopag. Treatment was discontinued after 16 weeks if no hematologic 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 six years and older with chronic ITP who have had an insufficient response to corticosteroids, immunoglobulins or splenectomy.

The most common side effects of Revolade when used to treat patients with chronic HCV and antiviral agents include fever, feeling very tired, chills, headache, cough, nausea, diarrhoea, unusual hair loss or thinning, muscle pain, itching, feeling weak, difficulty sleeping, loss of appetite, flu-like symptoms, and swelling of the hands, ankles or feet.

The most common side effects of Revolade when used to treat patients with severe aplastic anaemia (SAA) include cough, headache, shortness of breath, pain in the nose and throat, runny nose, abdominal pain, diarrhoea, bruising, joint pain, muscle spasms, pain in extremities, dizziness, feeling very tired, fever, inability to sleep (insomnia). Common side effects that may show up in blood tests include increase in some liver enzymes and laboratory tests that may show abnormal changes to the cells in the bone marrow.