EMA has recommended granting a marketing authorisation in the EU for Oxbryta (voxelotor) for the treatment of haemolytic anaemia (excessive breakdown of red blood cells) due to sickle cell disease in patients 12 years of age and older.
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Oxbryta is to be used on its own or in combination with hydroxycarbamide (also known as hydroxyurea).
Sickle cell disease is a genetic condition in which the red blood cells become rigid and sticky and change from being disc-shaped to being crescent-shaped (like a sickle). The change in shape is caused by the presence of an abnormal form of haemoglobin (the protein in red blood cells that carries oxygen around the body).
In patients with sickle cell anaemia, the abnormal sickle-shaped red blood cells block the blood vessels, restricting the flow of blood to organs, such as the heart, lungs and spleen. This situation causes episodes of acute pain called vaso-occlusive crisis (VOC).
Furthermore, these abnormal red blood cells are destroyed at a faster rate than normal, leading to a condition called haemolytic anaemia. Vaso-occlusive crisis (VOC) and haemolytic anaemia are the most common complications of sickle cell disease and are frequent causes of visits to emergency departments and hospitalisation.
Currently, most patients with sickle cell disease are treated with hydroxyurea and crizanlizumab, medicines for preventing VOC.
However, there is a high unmet need for medicines to treat haemolytic anaemia, which is experienced to various degrees by all patients. Available treatment options are limited to blood transfusions and allogenic hematopoietic stem cell transplantation (a procedure where the patient receives stem cells to help the bone marrow produce healthy blood cells). Therefore, new medicines for this manifestation of the disease are needed.
The active substance of Oxbryta is voxelotor, a small molecule which attaches to and stabilises haemoglobin, preventing haemoglobin polymerization (i.e. formation of abnormal haemoglobin) that causes the red blood cells to become sickle shaped.
The main study that EMA’s recommendation is based on was a Phase 3, randomised, double blind, placebo controlled, multicentre study.
The study investigated the safety and efficacy of voxelotor in 274 patients with sickle cell disease aged 12 to 65 years. Patients enrolled in the clinical trial had a baseline haemoglobin level between 5.5 and 10.5 g/dL. 90 patients received 1500 mg of voxelotor, 92 patients received 900 mg of voxelotor and 92 patients received a placebo.
After 24 weeks of treatment, 51.1% of patients treated with 1,500 mg of voxelotor had a greater than 1 g/dl increase in their haemoglobin levels compared to 6.5% of those receiving placebo. These results were observed when Oxbryta was used on its own or in combination with hydroxyurea, which is the standard treatment for patients with sickle cell disease.
The most common side effects reported in clinical trials for Oxbryta included headache, diarrhoea and abdominal pain. ■