Rigel’s and AstraZeneca’s R788 (fostamatinib) – an oral Syk inhibitor for rheumatoid arthritis

Posted by lifetech on March 30th, 2011

Rigel’s and AstraZeneca’s R788 is an oral, small molecule therapy in phase III rheumatoid arthritis (RA) trials. It modulates inflammation via inhibition of splenic tyrosine kinase (Syk). If successful, R788 will compete in a market currently dominated by biologics that inhibit TNF-α — all agents that are administered by injection or intravenous infusion. While a ‘pill’ would seem far preferable to a ‘poke’, particularly for a chronic disease, phase III trials still must show robust efficacy and an appropriate safety profile. The companies have reported data from all three phase II TASKi trials and have begun their phase III OSKIRA trial program. Of special interest, the TASKi3 trial results differed from those of the TASKi 1 and 2 trials. Our latest report explores the possible reasons for TASKi3’s failure and what that means for the ongoing phase III trials. The report also explores FDA guidance on RA drug development and the degree to which the ongoing phase III program meets those standards. Finally, phase II trials have identified some emerging safety signals which need further characterization. Thus, the question remains as to how much risk regulators, patients and the marketplace will accept in exchange for the convenience of an oral treatment for this debilitating disease.