OREANDA-NEWS. March 24, 2016. Pfizer Inc. (NYSE:PFE) announced today that the European Medicines Agency (EMA) has accepted for review the Marketing Authorization Application (MAA) for XELJANZ® (tofacitinib citrate) 5 mg tablets twice daily for the treatment of patients with moderate to severe rheumatoid arthritis (RA) who have had an inadequate response or intolerance to methotrexate (MTX). The EMA will now initiate its review of the XELJANZ MAA.

This application provides additional information to the original MAA submission, including data from the Phase 3 ORAL (Oral Rheumatoid Arthritis Phase 3 TriaLs) global development program in RA. This program consisted of six completed clinical trials, in addition to two open-label long-term extension (LTE) studies, one of which is still ongoing. To date, the ORAL development program has accumulated more than 19,400 patient-years of drug exposure having been studied in more than 6,100 patients including follow-up observations of up to eight years in the LTE study.1

“We are committed to making XELJANZ available to RA patients in the EU. The up to eight years of data that we have accumulated demonstrate our commitment to understanding the efficacy and safety of XELJANZ in patients living with RA,” said Michael Corbo, Category Development Lead, Inflammation & Immunology, Pfizer Global Innovative Pharmaceuticals Business. “We look forward to working together with the EMA on its review.”

XELJANZ is the only oral Janus kinase (JAK) inhibitor approved in more than 45 countries around the world for the treatment of moderate to severe RA. Since XELJANZ was first approved in the U.S. in 2012, it has been prescribed to more than 50,000 patients worldwide.

About Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease that causes a range of symptoms, including pain and swelling in the joints,2,3 particularly those in the hands, feet and knees.3 Although the exact cause of RA is unknown,3 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.3 Some people are at increased risk of developing RA, including people with a family history of RA, smokers and women.4 Three times as many women are affected by RA compared to men.3 RA affects approximately 23.7 million people worldwide5 and 1.6 million people in the United States.6,7 It can develop at any time during adulthood, but it usually occurs between 40 and 70 years of age.3

About XELJANZ (tofacitinib citrate)

XELJANZ® is a prescription medicine called a Janus kinase (JAK) inhibitor.

As the developer of XELJANZ, Pfizer is a leader in JAK innovation. XELJANZ does not require injections or infusions. XELJANZ can be taken with or without methotrexate.

XELJANZ is approved in more than 45 countries around the world for the treatment of moderate to severe RA as a second-line therapy after failure of one or more disease-modifying antirheumatic drugs (DMARDs).

Pfizer is committed to advancing the science of JAK inhibition and enhancing understanding of XELJANZ through a robust clinical development program.

About XELJANZ XR (tofacitinib citrate) extended-release

Pfizer has also developed an extended-release formulation, XELJANZ XR 11 mg, the first and only once-daily oral JAK inhibitor for the treatment of moderate to severe RA, approved in the United States.

XELJANZ/XELJANZ XR U.S. Label Information

XELJANZ/XELJANZ XR is a prescription medicine called a Janus kinase (JAK) inhibitor. XELJANZ/XELJANZ XR is used to treat adults with moderately to severely active rheumatoid arthritis in which methotrexate did not work well. XELJANZ/XELJANZ XR may be used as a single agent or in combination with methotrexate (MTX) or other non-biologic disease-modifying antirheumatic drugs (DMARDs). Use of XELJANZ/XELJANZ XR in combination with biologic DMARDs or potent immunosuppressants, such as azathioprine and cyclosporine is not recommended.

  • It is not known if XELJANZ/XELJANZ XR is safe and effective in people with hepatitis B or C.
  • XELJANZ/XELJANZ XR is not for people with severe liver problems.
  • It is not known if XELJANZ/XELJANZ XR is safe and effective in children.

Important Safety Information

  • XELJANZ/XELJANZ XR can lower the ability of the immune system to fight infections. Some people can have serious infections while taking XELJANZ/XELJANZ XR, including tuberculosis (TB), and infections caused by bacteria, fungi, or viruses that can spread throughout the body. Some people have died from these infections. Healthcare providers should test patients for TB before starting XELJANZ/XELJANZ XR, and monitor them closely for signs and symptoms of TB and other infections during treatment. People should not start taking XELJANZ/XELJANZ XR if they have any kind of infection unless their healthcare provider tells them it is okay.
  • People may be at a higher risk of developing shingles.
  • XELJANZ/XELJANZ XR may increase the risk of certain cancers by changing the way the immune system works. Lymphoma and other cancers, including skin cancers, can happen in patients taking XELJANZ/XELJANZ XR.
  • The risks and benefits of treatment should be considered prior to initiating XELJANZ/XELJANZ XR in patients with chronic or recurrent infection; who have been exposed to tuberculosis; with a history of a serious or an opportunistic infection; who have resided or traveled in areas of endemic tuberculosis or endemic mycoses; or with underlying conditions that may predispose them to infection.
  • Viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster), was observed in clinical studies with XELJANZ.
  • Use of live vaccines should be avoided concurrently with XELJANZ/XELJANZ XR. Update immunizations in agreement with current immunization guidelines prior to initiating XELJANZ/XELJANZ XR therapy.
  • Some people who have taken XELJANZ with certain other medicines to prevent kidney transplant rejection have had a problem with certain white blood cells growing out of control (Epstein Barr virus-associated post-transplant lymphoproliferative disorder).
  • Some people taking XELJANZ/XELJANZ XR can get tears in their stomach or intestines. This happens most often in people who also take nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, or methotrexate.
  • XELJANZ/XELJANZ XR should be used with caution in patients who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis), or who have a narrowing within their digestive tract. Patients should tell their healthcare provider right away if they have fever and stomach-area pain that does not go away or a change in bowel habits.
  • XELJANZ/XELJANZ XR can cause changes in certain lab test results including low blood cell counts, increases in certain liver tests, and increases in cholesterol levels. Healthcare providers should do blood tests before starting patients on XELJANZ/XELJANZ XR and while they are taking XELJANZ/XELJANZ XR, to check for these side effects. Normal cholesterol levels are important to good heart health. Healthcare providers may stop XELJANZ/XELJANZ XR treatment because of changes in blood cell counts or liver test results.
  • Use of XELJANZ/XELJANZ XR in patients with severe hepatic impairment is not recommended.
  • Patients should tell their healthcare providers if they plan to become pregnant or are pregnant.

It is not known if XELJANZ/XELJANZ XR will harm an unborn baby. To monitor the outcomes of pregnant women exposed to XELJANZ/XELJANZ XR, 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/XELJANZ XR, including boxed warning and Medication Guide: http://labeling.pfizer.com/ShowLabeling.aspx?id=959.

Pfizer Inc.: Working together for a healthier world®

At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of healthcare products. Our global portfolio includes medicines and vaccines as well as many of the world's best-known consumer healthcare products. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 150 years, Pfizer has worked to make a difference for all who rely on us. For more information, please visit us at www.pfizer.com. In addition, to learn more, follow us on Twitter at @Pfizer and@Pfizer_News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.

DISCLOSURE NOTICE: The information contained in this release is as of March 23, 2016. 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 a potential indication in Europe for XELJANZ® (tofacitinib citrate) 5 mg tablets twice daily for the treatment of patients with moderate to severe rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate (the “potential indication”), including its potential benefits, that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include, among other things, the uncertainties inherent in research and development, including the possibility of unfavorable clinical trial results, including unfavorable new clinical data and additional analyses of existing clinical data; whether and when the European Medicines Agency may approve the Marketing Authorization Application for the potential indication and whether and when regulatory authorities in any other jurisdictions where applications are pending or may be submitted for the potential indication may approve any such applications, which will depend on the assessment by such regulatory authorities of the benefit-risk profile suggested by the totality of the efficacy and safety information submitted; decisions by regulatory authorities regarding labeling and other matters that could affect the availability or commercial potential of XELJANZ and XELJANZ XR; 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, 2015 and in its subsequent reports on Form 10-Q, including in the sections thereof captioned “Risk Factors” and “Forward-Looking Information and Factors That May Affect Future Results”, as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S. Securities and Exchange Commission and available at www.sec.gov and www.pfizer.com.

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1 CII_Adhoc_944_P123LTE_21AUG2015. Tofacitinib Protocol P123LTE. Table 1.4.1.1.A

2 Lee DM, Weinblatt ME. Rheumatoid arthritis. Lancet. 2001; 358:903-911.

3 Medline Plus, “Rheumatoid Arthritis” Accessed 11 October 2011. Available athttp://www.nlm.nih.gov/medlineplus/ency/article/000431.htm.

4 Mayo Clinic, “Rheumatoid Arthritis.” Accessed 14 September 2011. Available athttp://www.mayoclinic.com/health/rheumatoid-arthritis/DS00020/DSECTION=risk-factors.

5 Annals of Rheumatic Diseases, “The global burden of rheumatoid arthritis: estimates from the Global Burden of Disease 2010 study.” Accessed 14 July 2015. Available at http://ard.bmj.com/content/early/2014/02/18/annrheumdis-2013-204627.

6 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.

7 Howden, L., Meyer, J., 2010 U.S. Census Bureau results --- U.S. Census Bureau, 2010 Census Summary File 1.