AstraZeneca released top-line results of OSKIRA-1, a phase III study to assess the efficacy and safety of fostamatinib, the first oral spleen tyrosine kinase (SYK) inhibitor in development for rheumatoid arthritis (RA). OSKIRA-1 had two primary endpoints: assessing signs and symptoms of RA as measured by ACR20 response rates, and an X-ray endpoint known as mTSS (modified Total Sharp Score).
In the OSKIRA-1 study, fostamatinib achieved a statistically significant improvement in ACR20 response rate at 24 weeks in both the 100mg twice daily group and the group that received 100mg twice daily for four weeks followed by 15 mg once daily (49%, p<0.001 and 44%, p=0.006, respectively) compared to placebo (34%). Fostamatinib did not demonstrate a statistically significant difference in mTSS compared to placebo at 24 weeks for either dose (p=0.252 and p=0.170, respectively).
The safety and tolerability findings for fostamatinib observed in the OSKIRA-1 study were generally consistent with those previously reported for the TASKi phase II program. The most commonly reported adverse events were typical of those seen in earlier studies, including hypertension, diarrhea, nausea, headache and nasopharyngitis.
"These top-line results provide important information on the efficacy and safety of fostamatinib and demonstrate that the compound has an effect on the signs and symptoms of rheumatoid arthritis,” said Briggs Morrison, MD, executive vice president of global medicines development and chief medical officer. “We will await the results of the remaining phase III studies, OSKIRA-2 and OSKIRA-3, to further evaluate and characterize the profile of fostamatinib as a potential treatment for rheumatoid arthritis."
OSKIRA-1 randomized 923 patients who had experienced an inadequate response to methotrexate (MTX) and, over a 24-week period, evaluated the effectiveness of two dosing regimens of fostamatinib (100mg twice daily or fostamatinib 100mg twice daily for four weeks followed by 150 mg once daily) in combination with MTX versus placebo in combination with MTX. Patients on fostamatinib remained on treatment in OSKIRA-1 for 12 months.
The OSKIRA-2 and OSKIRA-3 results are expected later in the second quarter of 2013.