Syk inhibitors have had a rough ride, with both Rigel and Portola running into significant issues in clinical development.

Rigel and partner Astra Zeneca released data from a Phase 2 Rheumatoid Arthritis study, summarized here:

“In the study known as OSKIRA-1, two doses of fostamatinib significantly improved the signs and symptoms of rheumatoid arthritis compared to a placebo following 24 weeks of treatment. However, fostamatinib failed to show improvements over placebo in bone erosion and joint-space narrowing as measured by X-ray.” from http://www.thestreet.com/story/11888193/1/astra-rigel-arthritis-pill-posts-mixed-trial-results.html).

Sadly thats about all you need to know about fostamatinib, especially given that earlier data have been unimpressive as we discussed in December. There is no clear role for this drug in RA given the label granted to Pfizer for their JAK inhibitor tofacitinib, approved for use as second line therapy for RA. Tofacitinib also has shown clear evidence of protection from joint damage, something fostamatinib has failed to do.

Fostamatinib is apparently moving forward in multiple oncology indications, and therein may lie its future, if it has one.

Portola’s Syk inhibitor, licensed by Biogen Idec, is in development limbo, and the clinical trial in RA was withdrawn. Whether this is due to toxicity issues, efficacy concerns, or commercial strategy is not known, as Biogen has not provided an update on this drug.

In the meantime companies continue to focus on kinases that signal downstream of Syk, notably Btk and PI3K. While PI3K inhibition may carry too much toxicity for use outside of oncology, Btk inhibitors appear to be safe enough to develop in autoimmunity and inflammation. We will continue to watch the development of small molecule inhibitors in this space, and anticipate success for novel Btk inhibitors.