Pfizer Inc. announced today top-line results from ORAL Start (A3921069), a phase 3 study of the investigational agent tofacitinib, a novel, oral Janus kinase (JAK) inhibitor for the treatment of adults with moderate-to-severe active rheumatoid arthritis (RA).

ORAL Start, an ongoing two-year study in methotrexate (MTX)-naïve patients with moderate-to-severe active RA, randomized to receive tofacitinib 5 or 10 mg twice-daily (BID) as monotherapy or MTX, met its primary endpoints at both the 5 and 10 mg BID doses. Tofacitinib 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), and in reducing signs and symptoms of RA, as measured by ACR70 response rates. Both primary endpoints assessed tofacitinib versus MTX at six months. The data reported are from a planned analysis at one year.

No new safety signals emerged in the ORAL Start study, and the safety profile of tofacitinib remained consistent with that seen previously in the clinical development program. 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.

A detailed analysis of the ORAL Start findings will be submitted to a future scientific meeting.

Pfizer also noted during its second quarter earnings call that the US Food and Drug Administration (FDA) has recently requested additional analysis of the existing data in the tofacitinib New Drug Application (NDA). Pfizer is planning to provide FDA with this information in early August and, given this timing, it anticipates that FDA may require additional time beyond the August 21 Prescription Drug User Fee Act (PDUFA) date to review the information.

ORAL Start is an ongoing two-year study that randomized 958 patients with moderate-to-severe active RA who were naïve to MTX to receive tofacitinib monotherapy 5 or 10 mg BID or MTX. The primary objectives of ORAL Start are to compare preservation of joint structure, treatment of signs and symptoms and safety and tolerability with tofacitinib 5 or 10 mg BID versus MTX. Results are from a planned 12-month interim analysis.

Tofacitinib is a novel, oral JAK inhibitor that is being investigated as a targeted immunomodulator and disease-modifying therapy for RA. Unlike recent therapies for RA, which are directed at extracellular targets such as pro-inflammatory cytokines, tofacitinib takes a novel approach targeting the intracellular pathways that operate as hubs in the inflammatory cytokine network.

Tofacitinib was evaluated in the phase 3 ORAL (Oral Rheumatoid Arthritis Phase 3 TriaLs) program, a comprehensive, multi-study, global clinical development program that included approximately 5,000 patients who represent a broad cross-section of the RA patient population. In these trials, tofacitinib was studied as monotherapy or in combination with non-biologic disease-modifying antirheumatic drugs (or DMARDs), mostly MTX, in patients who were MTX-naïve or who had a previous inadequate response to DMARDs, including TNF inhibitors.

Tofacitinib is currently under review for the treatment of moderate–to-severe active RA by several regulatory agencies around the world, including in the United States, Europe and Japan. If approved, tofacitinib would be the first RA treatment in a new class of medicines known as JAK inhibitors.