NEW YORK -- (BUSINESS WIRE) -- Pfizer Inc. (NYSE:PFE) announced today the publication of two-year results from the ORAL Start study in the June 19 issue of The New England Journal of Medicine. ORAL Start is a 24-month Phase 3 study in patients with moderately to severely active rheumatoid arthritis who had not previously received methotrexate. The study showed that XELJANZ (tofacitinib citrate) 5 mg and 10 mg twice daily, as monotherapy (e.g., taken without methotrexate), inhibited the progression of structural damage and reduced the signs and symptoms of rheumatoid arthritis, and was statistically significantly superior to methotrexate on these measures at Month 6 (primary endpoint) and at all measured time points up to 24 months. XELJANZ is not indicated in patients who had not previously received methotrexate. The safety profile of XELJANZ in the ORAL Start study was consistent with that seen previously in the clinical development program.
In the United States, XELJANZ 5 mg tablets are indicated for the treatment of adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate. XELJANZ may be used alone or in combination with methotrexate or other non-biologic, disease-modifying antirheumatic drugs (DMARDs). Use of XELJANZ in combination with biologic DMARDs or potent immunosuppressants, such as azathioprine and cyclosporine, is not recommended. The recommended dose is a 5 mg pill taken twice daily.
“This study showed that XELJANZ taken by itself was statistically significantly superior to methotrexate in measures of clinical, radiographic and functional efficacy rheumatoid arthritis outcomes, and these results were sustained over two years,” said lead investigator Roy M. Fleischmann, MD, professor, Metroplex Clinical Research Center, Dallas, Texas. “These results also add to the information on the efficacy and safety of XELJANZ as monotherapy.”
The ORAL Start study was a 24-month Phase 3 randomized, double-blind, controlled trial in which 956 patients with moderately to severely active rheumatoid arthritis who had not previously received methotrexate were randomized to receive XELJANZ 5 mg or 10 mg twice daily or to methotrexate dose-titrated over 8 weeks to 20 mg weekly. As previously announced, both doses of XELJANZ met the study’s co-primary efficacy endpoints: reduction of progression of radiographic measures of disease as measured by average change from baseline in van der Heijde modified Total Sharp Score (mTSS)[0.18 and 0.04 (both P<0.001) for XELJANZ 5 mg and 10 mg twice daily, respectively, versus 0.84 for methotrexate], and clinical response as measured by ACR70 response rates, a measure of at least 70% reduction in signs and symptoms of rheumatoid arthritis [25.5% and 37.7% for XELJANZ 5 mg and 10 mg twice daily, respectively (both P<0.001), versus 12.0% for methotrexate], at Month 6. ORAL Start also evaluated improvement in physical function as measured by mean change from baseline in the Health Assessment Questionnaire Disability Index (HAQ-DI)[-0.83 and -0.94 (both P<0.001) for XELJANZ 5 mg and 10 mg twice-daily, respectively, versus -0.58 for methotrexate], at Month 6. These results were sustained at all measured time points up to 24 months.
The six- and 12-month radiographic data from this study were recently added to the XELJANZ U.S. label (February, 2014) as part of an FDA approved label update.
“The publication of the ORAL Start data in The New England Journal of Medicine marks the sixth Phase 3 study in the XELJANZ clinical program to be published in a major medical journal,” said Dr. Steven Romano, Global Medicines Development Lead for the Pfizer Global Innovative Pharmaceutical business. “The publication of all of the completed XELJANZ Phase 3 rheumatoid arthritis clinical studies in such respected publications speaks to the significance and clinical relevance of the data for XELJANZ.”
The safety profile of XELJANZ in the ORAL Start study was consistent with that seen previously in the clinical development program. The incidence of adverse events, serious adverse events and discontinuations due to adverse events were similar across groups. Most adverse events were mild or moderate and the most frequently reported adverse events in all groups were infections. Herpes zoster (shingles) occurred in 4.0% of patients on XELJANZ and 1.1% of patients on methotrexate. Confirmed malignancies developed in five patients treated with XELJANZ and one patient treated with methotrexate. XELJANZ was associated with increases in average serum creatinine and lipid levels.
XELJANZ U.S. Label Information
XELJANZ is a prescription medicine called a Janus kinase (JAK) inhibitor. XELJANZ is used to treat adults with moderately to severely active rheumatoid arthritis in which methotrexate did not work well.
Important Safety Information
It is not known if XELJANZ will harm an unborn baby. To monitor the outcomes of pregnant women exposed to XELJANZ, a registry has been established. Physicians are encouraged to register patients and pregnant women are encouraged to register themselves by calling 1-877-311-8972.
Please click the direct link to the full prescribing information for XELJANZ, including boxed warning and Medication Guide: http://labeling.pfizer.com/ShowLabeling.aspx?id=959.
About Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease that typically affects the hands and feet, although any joint lined by the synovial membrane can be affected.1 RA causes a range of symptoms, including stiffness and swelling in the joints,2 particularly those in the hands, feet and knees.1 Although the exact cause of RA is unknown,1 it is considered to be an autoimmune disease, because the immune system in people with RA mistakes the body’s healthy tissues for a threat and attacks them.1 Some people are at increased risk of developing RA, including people with a family history of RA, smokers and women.3 Three times as many women are affected by RA compared to men.2 RA affects approximately 23.7 million people4 worldwide and 1.6 million people in the United States.5,6 It can develop at any time during adulthood, but it usually occurs between 40 and 70 years of age.2
Pfizer Inc.: Working together for a healthier world®
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DISCLOSURE NOTICE: The information contained in this release is as of June 18, 2014. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments.
This release contains forward-looking information about XELJANZ (tofacitinib citrate), including its potential benefits, that involves substantial risks and uncertainties. Such risks and uncertainties include, among other things, whether and when the FDA will assess the benefit: risk profile of the 10 mg twice-daily dose; and competitive developments.
A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2013 and in its subsequent reports on Form 10-Q and Form 8-K.
1 Medline Plus, “Rheumatoid Arthritis” Accessed 11 October 2011. Available at http://www.nlm.nih.gov/medlineplus/ency/article/000431.htm.
2 Lee DM, Weinblatt ME. Rheumatoid arthritis. Lancet. 2001; 358:903-911.
3 Mayo Clinic, “Rheumatoid Arthritis.” Accessed 14 September 2011. Available at http://www.mayoclinic.com/health/rheumatoid-arthritis/DS00020/DSECTION=risk-factors.
4 World Health Organization, “The Global Burden of Disease, 2004 Update.” Accessed 13 March 2012. Available at http://www.who.int/healthinfo/global_burden_disease/GBD_report_2004update_full.pdf.
5 Sacks, J., Lou, Y., Helmick, C. Prevalence of Specific Types of Arthritis and Other Rheumatic Conditions in the Ambulatory Health Care System in the United States 2001-2005. Arthritis Care and Research. 2010. 62(4): 460- 464.
6 Howden, L., Meyer, J., 2010 U.S. Census Bureau results --- U.S. Census Bureau, 2010 Census Summary File 1.