AstraZeneca's Fostamatinib Improves Outcomes of RA Patients

A phase II study of AstraZeneca’s new oral syk inhibitor, fostamatinib (R788), proves to be more effective than placebo in treating rheumatoid arthritis (RA).

Fostamatinib (R788) significantly improved outcomes of patients with RA who responded inadequately to ongoing treatment with methotrexate (MTX). The results will be published in The New England Journal of Medicine.

The experimental drug was recently in-licensed from Rigel Pharmaceuticals, Inc. The six-month phase IIb study completed by Rigel, known as TASKi2, demonstrated that 67% of patients taking fostamatinib 100mg twice daily achieved the primary efficacy endpoint at six months, which was significantly higher than placebo. Also, 36% of patients achieved an ACR 20 response after just one week. The most common adverse events included diarrhea and upper respiratory infection.

“In this study, we saw a significant clinical benefit in this rheumatoid arthritis population and a manageable safety profile,” said Mark C. Genovese, Division of Rheumatology, Stanford University, Palo Alto, CA, in a press release. “Based on the data, further study of fostamatinib as an oral agent for the treatment of patients with rheumatoid arthritis is certainly warranted.”

Fostamatinib is the first oral syk inhibitor in development as a novel therapeutic approach for RA. It is thought to reversibly block signalling in multiple cell types involved in inflammation and tissue degradation in RA.

The patients in the study had active RA, despite treatment with MTX alone, and were given either fostamatinib 100mg twice daily (bid), fostamatinib 150mg once daily (qd), or placebo. Both fostamatinib groups reported significant clinical.

After six months, the ACR 20 response was achieved by significantly more patients in both the fostamatinib 100mg bid group and the fostamatinib 150mg qd group than the placebo group. The ACR 50 response rates were 43%, 32%, and 19% for the fostamatinib 100mg bid group, 150mg qd group, and placebo group, respectively. The ACR 70 response rates were 28%, 14%, and 10% for the fostamatinib 100mg bid group, 150mg qd group, and placebo group, respectively. In addition, the DAS 28 remission rate was significantly higher in both the fostamatinib 100mg bid group and the fostamatinib 150mg qd group, compared to the placebo group.

The most common drug-related adverse events in the study were diarrhea, upper respiratory infection, and neutropenia. Hypertension occurred more frequently in fostamatinib treated patients than placebo.

AstraZeneca plans to begin a phase III clinical trial for fostamatinib, which will be called OSKIRA (Oral Syk Inhibition in Rheumatoid Arthritis), in the second half of 2010.