Many different immunosuppressant drugs are already available, being used for organ transplantation and also in autoimmune diseases such as psoriasis, rheumatoid arthritis and lupus. However, they target molecules that are widely expressed and as a result cause numerous side effects, many of them serious, such as nephrotoxicity, hyperlipidaemia and neurotoxicity.
By hitting a target that is exclusively expressed in the immune system, a more specific mode of action should be possible, and one that is being investigated is Janus kinase 3, or JAK-3, one of the many cytokines that is required for immune cell development and homeostasis. Pfizer is developing a JAK-3 inhibitor, CP-690550, which is selective for JAK-3 and no other form of JAK, and thus should cause fewer adverse events.
Trials have been carried out in a number of conditions. In one, 61 new kidney transplant patients were given 15 or 30mg of the drug or tacrolimus in a multicentre randomised, parallel group, open label study, along with steroids and an IL-2 receptor antagonist.1 No deaths, transplant failure or malignancies were seen in the six months after the transplant, and those given the higher dose were more likely to contract infections, but serum lipids rose more in the CP-690550 group.
It has also been investigated in rheumatoid arthritis. In the Phase IIa randomised double blind, placebo controlled trial in 264 subjects, they were given doses of 5, 15 or 30mg twice a day for six weeks.2,3 Lipid levels rose in a dose dependent manner, and all doses were effective in improving the symptoms of arthritis. Significant improvements in pain were seen in the two higher doses, and also in the lower dose after four weeks. Trials are continuing for both indications.