Pfizer Inc. (NYSE: PFE) announced today that 14 abstracts for tofacitinib, an investigational oral Janus kinase (JAK) inhibitor for the treatment of adults with moderate-to-severe active rheumatoid arthritis (RA), will be presented at the American College of Rheumatology (ACR) / Association of Rheumatology Health Professionals (ARHP) 2012 Annual Meeting, which is being held November 9-14 in Washington, D.C.
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. The FDA has provided an anticipated Prescription Drug User Fee Act (PDUFA) date of November 21, 2012. If approved, tofacitinib would be the first RA treatment in a new class of medicines known as JAK inhibitors and the first new oral disease-modifying antirheumatic drug (or DMARD) for RA in more than 10 years.
Results Being Presented for Phase 3 Studies, ORAL Start and ORAL Scan; Long-Term Safety and Efficacy Data Up To 48 months will also be Presented
- ORAL Start (A3921069), an ongoing Phase 3, 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. In this study, tofacitinib monotherapy was found to be superior to MTX, with statistically significant changes shown in inhibiting structural damage as measured by change from baseline in van der Heijde modified Total Sharp Score (mTSS) and in reducing signs and symptoms of RA as measured by ACR70 response rates, both assessed at six months. Secondary endpoints, including ACR20 and ACR50 responses, DAS-defined remission (DAS28-4(ESR) <2.6), and mean change in HAQ-DI, were statistically significantly greater with tofacitinib versus MTX at all time points. No new safety signals emerged in the study and the overall safety profile of tofacitinib remained consistent with that seen previously in the RA clinical development program. Results are from a pre-specified planned analysis at one year. “Radiographic, Clinical and Functional Comparison of Tofacitinib Monotherapy Versus Methotrexate in Methotrexate-Naïve Patients with Rheumatoid Arthritis”[Abstract #27194; Tuesday, November 13, 2012 at 2:45 p.m. EST]
- Results from a two-year analysis of ORAL Scan (A3921044), a completed Phase 3 study in patients with moderate-to-severe active RA who had an inadequate response to MTX, will also be presented. Patients were randomized to receive tofacitinib 5 or 10 mg BID or placebo, in each case with background MTX. Primary outcomes from the one-year analysis from ORAL Scan were previously reported at the ACR 2011 Annual Scientific Meeting. 1 ,2 The two-year analysis evaluated consistency of the efficacy and safety profile of tofacitinib 5 or 10 mg BID in patients who remained on active treatment through 24 months. The two-year results showed that patients on tofacitinib maintained improvements in efficacy including reductions in signs and symptoms, inhibition of structural damage, and improvements in physical function through month 24. No new safety signals emerged. “Tofacitinib, an Oral Janus Kinase Inhibitor, in Combination with Methotrexate Reduced the Progression of Structural Damage in Patients with Rheumatoid Arthritis: Year 2 Efficacy and Safety Results From a 24-Month Phase 3 Study” [Abstract #26718; Monday, November 12, 2012].
- Data from a pooled analysis of two long-term, open-label extension studies (NCT00413699, NCT00661661) involving patients with moderate-to-severe RA who had participated in randomized Phase 2 or 3 studies of tofacitinib dosed at 5 or 10 mg BID showed a consistent safety profile and sustained efficacy over 48 months. Safety and efficacy were similar for patients receiving tofacitinib as monotherapy or with background nonbiologic disease-modifying antirheumatic drugs (DMARDs). Primary endpoints were adverse events and confirmed laboratory safety data. Secondary endpoints included ACR responses, DAS28-4(ESR) and HAQ-DI. “Tofacitinib, an Oral Janus Kinase Inhibitor, in the Treatment of Rheumatoid Arthritis: Open Label, Long-Term Extension Safety and Efficacy Up To 48 Months” [Abstract #27156; Monday, November 12, 2012].
The overall safety profile of tofacitinib was consistent across all aforementioned trials. Notable safety findings observed in the tofacitinib RA program include serious and other important infections, including tuberculosis and herpes zoster; malignancies, including lymphoma; gastrointestinal perforations; decreased neutrophil and lymphocyte counts; and lipid elevations. The most common serious adverse events were serious infections. The most commonly reported adverse events were upper respiratory tract infections, headache, nasopharyngitis and diarrhea.