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Investigational Kinase Inhibitor Fostamatinib Inferior to Humira in Phase II Trial
Key findings have been announced from the OSKIRA-4 trial — a phase IIb study of the investigational tyrosine kinase inhibitor fostamatinib (AstraZeneca) as an oral treatment for rheumatoid arthritis (RA).
The 6-month study evaluated improvements in the signs and symptoms of RA in 280 patients who were randomly assigned to receive fostamatinib as monotherapy, adalimumab (Humira, Abbott) as monotherapy, or placebo. The patients had not been treated with a disease-modifying antirheumatic drug (DMARD), were DMARD intolerant, or had shown an inadequate response to DMARDs. Three dosing regimens of fostamatinib were evaluated: 100 mg twice daily; 100 mg twice daily for 1 month followed by 100 mg once daily; and 100 mg twice daily for 1 month followed by 150 mg once daily.
The study had two primary objectives: a superiority comparison with placebo at 6 weeks and a non-inferiority analysis against adalimumab monotherapy at 24 weeks, as measured by changes from baseline in the Disease Activity Score 28 (DAS28) — a composite endpoint that assesses the signs and symptoms of RA in 28 joints.
Oral fostamatinib as monotherapy showed a statistically significant change in the DAS28 score from baseline compared with placebo at week 6 at dosages of 100 mg twice daily and 100 mg twice daily for 1 month followed by 150 mg once daily, but not at 100 mg twice daily for 1 month followed by 100 mg once daily.
More important, all of the ostamatinib monotherapy doses were inferior to adalimumab monotherapy at week 24 based on DAS28 scores.
Fostamatinib (previously known as R788) is the first kinase inhibitor with selectivity for spleen tyrosine kinase (SYK) that is in development as an oral treatment for RA. The drug blocks signaling in multiple cell types involved in inflammation and tissue degradation in RA and may inhibit the steps required for disease progression.
Further assessments of the risk–benefit profile of fostamatinib used in combination with a DMARD are being conducted in the pivotal OSKIRA phase III program, and the results are expected in the first half of 2013.
Source: AstraZeneca; December 13, 2012.