Pfizer has reported positive top-line results from the ORAL Start (A3921069) Phase 3 study evaluating tofacitinib in patients with moderate-to-severe active rheumatoid arthritis (RA).
The ongoing two-year study in methotrexate (MTX)-naïve patients randomised to receive tofacitinib 5mg or 10mg twice-daily (BID) as monotherapy or MTX, met its primary endpoints at both the 5mg and 10mg BID doses.
The primary objectives of the study are to compare preservation of joint structure, treatment of signs and symptoms and safety and tolerability with tofacitinib 5mg or 10mg BID versus MTX.
Tofacitinib, an oral Janus kinase (JAK) inhibitor, was found to be superior to MTX with statistically significant changes shown in inhibiting structural damage, as measured by change from baseline in modified Total Sharp Score (mTSS).
As measured by ACR70 response rates, Tofacitinib was found to be superior to MTX with statistically significant changes shown in reducing signs and symptoms of RA.
Both the primary endpoints assessed tofacitinib versus MTX at six months. The results are from a planned 12-month interim analysis.
The ORAL Start study did not note emergence of any new safety signals and the safety profile of tofacitinib remained consistent with that seen previously in the clinical development programme.
The safety findings observed in the overall tofacitinib RA programme include serious and other important infections, including tuberculosis and herpes zoster; malignancies, including lymphoma; decreased neutrophil counts and neutropenia; and lipid elevations.
Pfizer is considering providing the FDA with the information in response to the request made by the regulatory body to provide additional analysis of the existing data in the tofacitinib new drug application.