Ruxolitinib is in clinical development for acute graft versus host disease (aGvHD). After a donor stem cell transplant, the donor’s stem cells (the graft) may sometimes react against the host’s own cells. This is called GVHD. aGVHD is most likely to happen in the first three months after transplant. The symptoms depend on which parts of the body are affected. It often causes an itchy skin rash. If the bowel, the stomach or the liver are affected, the patient may have sickness and diarrhoea. aGVHD is graded by how severe it is. It goes from grade 1, which is mild, to grade 4 which is very severe. Current standard treatment includes the use of steroids but this is often associated with significant side effects. Steroid resistance in GvHD may also develop which is difficult to treat and associated with a high mortality.
Ruxolitinib works by blocking the action of enzymes known as Janus kinases (JAKs), which are involved in the production and growth of blood cells and immune function. By blocking JAKs, ruxolitinib reduces the abnormal production of blood cells, thereby reducing the symptoms of the diseases. Ruxolitinib is administered as oral tablets and if licenced, will offer a treatment option for patients with steroid-refractory aGvHD after allogeneic hematopoietic stem cell transplantation.
Avapritinib is in clinical development for the treatment of advanced systemic mastocytosis (SM) in adults. SM is a condition where mast cells grow uncontrollably and accumulate in body organs/tissues such as the skin, internal organs, lymph nodes and bones. Mast cells are immune cells that release inflammatory mediators that are important in the body’s allergic responses. When mast cells are present in large numbers there is a high release of these mediators leading to symptoms such as itching, fever, abdominal pain, nausea and vomiting. In advanced SM, mast cells collect in such high quantities that they lead to organ damage and dysfunction, bone fractures and anaemia.