Two Phase III Studies Confirm Benefits of Pfizer’s Tofacitinib Against Active RA

Pfizer reported positive topline data from two completed Phase III studies evaluating the oral JAK inhibitor tofacitinib (CP-690,550) in patients with active moderate-to-severe rheumatoid arthritis (RA). Both the 12-month Oral Standard study and 6-month Oral Step study met their primary endpoints in terms of a reduction in the signs and symptoms of RA as measured by ACR20 response rates, combined with improvements in physical function. Oral Standard and Oral Step were the final two pivotal trials in the five-study Phase III program for tofacitinib in RA. A sixth, long-term treatment study is ongoing.

In March Pfizer reported positive data from the Phase III placebo-controlled ORAL Sync study evaluating  tofacitinib in moderate-to-severe RA patients who had previously demonstrated inadequate response to a DMARD and who continued to receive background DMARD throughout the trial.  

The newly reported 12-month Oral Standard study included 717 patients with moderate-to-severe active RA who had previously responded inadequately to methotrexate therapy. Participants were randomized to receive either tofacitinib 5 mg or 10 mg twice a day, adalimumab 40 mg subcutaneously every other week, or placebo. After the first three months, nonresponding placebo-treated patients were moved over to one of the tofacitinib doses, and after six months all placebo-treated patients were switched over to tofacitinib therapy.

The Oral Step study enrolled 399 patients with moderate-to-severe active RA who had previously demonstrated an inadequate response to at least one TNF inhibitor. Participants were randomized to receive 5 mg or 10 mg tofacitinib twice daily, or placebo, in addition to stable background methotrexate. All placebo-treated patients were switched over to tofacitinib therapy at the three-month mark.

Oral and topical formulations of tofacitinib are in addition being evaluated in clinical trials for the treatment of a range of diseases and disorders. Oral tofacitinib is in Phase III trials against psoriasis and in Phase II development against psoriatic arthritis, ankyosing spondylitis, Crohn disease, ulcerative colitis, and transplant rejection. Phase II trials of topical tofacitinib are ongoing for the psoriasis and dry-eye indications.