Pfizer Inc. announced top-line results from the ORAL Scan phase 3 study (A3921044) of tofacitinib (development code: CP-690,550), formerly known as tasocitinib, an investigational, novel, oral JAK inhibitor. ORAL Scan is an ongoing two-year study in patients with moderate-to-severe active rheumatoid arthritis (RA) who had an inadequate response to methotrexate (MTX) and were randomized to receive tofacitinib 5 or 10 mg BID or placebo added to background MTX. The data reported are from a planned analysis at one year.
The ORAL Scan study met all primary endpoints at the 10 mg BID dose, showing statistically significant changes versus placebo in reducing signs and symptoms of RA, as measured by ACR20 response rates at six months; in reducing the progression of structural damage, as measured by change from baseline in modified Total Sharp Score (mTSS) at six months; in improving physical function, as measured by mean change in HAQ DI at three months; and in reaching DAS28-4(ESR) <2.6 at six months.
For the 5 mg BID dose, the study demonstrated statistically significant improvements versus placebo in ACR20 response rates at six months, but the difference from placebo in mTSS did not reach statistical significance at six months. Due to the pre-specified step-down statistical procedure, no further testing was performed on HAQ DI and DAS28-4(ESR) <2.6 for the 5 mg BID dose.
No new safety signals emerged in the ORAL Scan study. The efficacy and safety profile of tofacitinib in this study remains consistent with that seen previously in the clinical programme. A full analysis of the ORAL Scan efficacy and safety data will be submitted to a future scientific meeting.
ORAL Scan is an ongoing two-year study that randomized 800 patients with moderate-to-severe active RA who had an inadequate response to MTX to receive tofacitinib 5 or 10 mg BID or placebo added to background MTX. At the three month visit, non-responding placebo-assigned patients were advanced in a blinded fashion to a predetermined treatment of tofacitinib, 5 or 10 mg BID, for the remainder of the study. At the end of six months, all placebo-assigned patients were advanced to their predetermined tofacitinib treatment assignment in a blinded fashion for the remainder of the study. The two year data from this study are expected in 2012.
Tofacitinib is a novel, oral Janus kinase (JAK) inhibitor that is being investigated as a targeted immunomodulator and disease-modifying therapy for RA. More than 4,000 RA patients have been treated with tofacitinib in clinical trials to date. Unlike current therapies for RA, which are directed at extracellular targets such as pro-inflammatory cytokines, tofacitinib takes a novel approach, targeting the intracellular signaling pathways that operate as hubs in the inflammatory cytokine network.