Playing JAKs

How cytokine-level thinking is guiding Pfizer’s clinical immunology plans

A desire to improve upon marketed autoimmune drug Xeljanz tofacitinib, coupled with interesting biological findings, led Pfizer Inc. to develop a portfolio of selective Janus kinase inhibitors that are taking the target into new disease areas.

A broad Phase II program is designed to study each molecule in one or a couple of lead indications that could give hints about how it will perform in several others. Data emerging in the 2018-19 time frame will help the pharma find the most likely indications for monotherapy and combination regimens.

Xeljanz is an oral pan-JAK inhibitor approved to treat rheumatoid arthritis. Collectively, JAK kinases mediate the effects of cytokine signaling. There are four members of the JAK family: JAK-1, -2 and -3, and tyrosine kinase 2 (TYK2).

In RA, pan-JAK inhibition broadly suppresses the activity of TNF, growth factors and hormones, giving oral Xeljanz efficacy that has been shown to be comparable to marketed TNF inhibitors that

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