Givosiran as subcutaneous injection is in clinical development for the treatment of acute hepatic porphyria (AHP). AHP is a rare genetic condition in which patients lack certain enzymes needed to produce haem, a component of the blood pigment haemoglobin. As a result, substances for making haem accumulate in the body (particularly in the liver) and become toxic, causing attacks of severe abdominal pain, vomiting and nervous system disorders, such as seizures (fits), depression and anxiety. Some patients may also experience skin problems, with skin becoming oversensitive to light. AHP is life-threatening due to the possibility of paralysis and respiratory arrest during attacks and debilitating in the long term because of symptoms such as pain, nausea, seizures and skin blistering.
Givosiran is made of a short, synthetic strand of genetic material called ‘small interfering RNA’ (siRNA) that has been designed to interfere with the production of an enzyme involved in an early step in making haem. By blocking this early step of haem production in patients with AHP, givosiran is expected to prevent the next steps which produce substances that accumulate in the body and cause the symptoms of the disease.
Imetelstat is in clinical development for the treatment of relapsed/refractory low or intermediate-1 risk myelodysplastic syndrome (MDS) in transfusion-dependent patients, following erythropoiesis-stimulating agent (ESA) treatment. MDS are a group of disorders in which red blood cells, white blood cells, and platelets produced by the bone marrow do not grow and mature normally. MDS are long-term debilitating and life-threatening diseases. MDS patients may require repeated blood transfusions and currently have few treatment options.