From Pfizer:

Pfizer Announces Positive Top-Line Results from Two Phase 3 Trials of Oral Tofacitinib in Adults with Moderate-to-Severe Ulcerative Colitis

Monday, September 21, 2015 8:00 am EDT

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"We are encouraged by the results of the OCTAVE induction studies as ulcerative colitis is a chronic, and at times debilitating, disease that can be difficult to treat"

NEW YORK--(BUSINESS WIRE)--Pfizer Inc. announced today top-line results from two Phase 3 induction trials of tofacitinib 10 mg twice daily (BID) tablets in the Oral Clinical Trials for tofAcitinib in ulceratiVE colitis (OCTAVE) global clinical development program for the treatment of adults with moderate to severe ulcerative colitis (UC): OCTAVE Induction 1 (A3921094) and OCTAVE Induction 2 (A3921095). Both studies met their primary endpoints as measured by the proportion of patients receiving tofacitinib in remission at Week 8 compared to patients receiving placebo.

“We are encouraged by the results of the OCTAVE induction studies as ulcerative colitis is a chronic, and at times debilitating, disease that can be difficult to treat” said Rory O’Connor, MD, senior vice president and head of Global Medical Affairs, Global Innovative Pharmaceuticals Business, Pfizer Inc. “Pfizer remains committed to advancing the science of Janus kinase inhibition and enhancing understanding of tofacitinib, the first in this new class of medications being investigated for ulcerative colitis. We look forward to sharing the results of our ongoing Phase 3 maintenance study OCTAVE Sustain, when available, which will provide further information on tofacitinib in ulcerative colitis.”

No new or unexpected safety findings for tofacitinib were observed in the studies. Serious adverse events observed were similar to those seen in other clinical development programs for tofacitinib. Detailed analyses of OCTAVE Induction 1 and OCTAVE Induction 2, including additional efficacy and safety data, will be submitted for presentation at a future scientific meeting.

OCTAVE Induction 1 and OCTAVE Induction 2 are two identical Phase 3 placebo-controlled studies evaluating induction of remission by oral tofacitinib 10 mg BID in adult patients with moderate to severe UC. A total of 598 patients in OCTAVE Induction 1 and 541 patients in OCTAVE Induction 2 were randomized to tofacitinib 10 mg BID or placebo treatment groups.

The OCTAVE global clinical development program includes three Phase 3 studies, OCTAVE Induction 1, OCTAVE Induction 2, and OCTAVE Sustain (A3921096), as well as a long-term extension trial, OCTAVE Open (A3921139). Results for OCTAVE Sustain are anticipated by the end of 2016. These four studies will form the potential submission package to regulatory authorities for a potential UC indication.

About Ulcerative Colitis

UC is a chronic, often debilitating inflammatory bowel disease that affects millions of people worldwide.1,2,3 It is believed that UC is the result of complex interactions between multiple factors that include the environment, genetic predisposition, immune response, and the gut microbiome in the colon or intestines.4 It can cause abdominal pain, fever, weight loss and chronic, bloody diarrhea. UC can have an effect on work, family and social activities.5 In up to one-third of patients with UC, treatment is not completely successful or complications arise. Under these circumstances, surgery to remove the colon (colectomy) may be considered. Even after surgery, certain symptoms of UC may still persist. 6,7,8

About Tofacitinib

Tofacitinib (brand name XELJANZ®) is a prescription medicine called a Janus Kinase (JAK) Inhibitor.

XELJANZ is the first and only JAK inhibitor approved in over 40 countries around the world for the treatment of moderate to severe rheumatoid arthritis (RA) as a second-line therapy after failure of one or more disease-modifying antirheumatic drugs (DMARDs). The benefit:risk profile of XELJANZ in RA has been studied in approximately 6,200 patients in the global clinical development program for XELJANZ in moderate to severe RA. A new drug application (NDA) for XELJANZ 11 mg once-daily modified release for the treatment of moderate to severe RA is under review with the U.S. Food & Drug Administration (FDA). In the United States, XELJANZ has a boxed warning for serious infections and malignancies.

Pfizer is committed to advancing the science of JAK inhibition and enhancing understanding of XELJANZ through a robust clinical development program in a range of immune-mediated inflammatory conditions in the areas of rheumatology, dermatology and gastroenterology.

XELJANZ U.S. Label Information

XELJANZ is a prescription medicine called a Janus kinase (JAK) inhibitor. The recommended dose is 5 mg twice-daily (BID). XELJANZ is used to treat adults with moderately to severely active rheumatoid arthritis in which methotrexate did not work well. XELJANZ may be used as a single agent or in combination with MTX 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.

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

Important Safety Information

• XELJANZ can lower the ability of the immune system to fight infections. Some people have serious infections while taking XELJANZ, 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, and monitor them closely for signs and symptoms of TB and other infections during treatment. People should not start taking XELJANZ 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 may increase the risk of certain cancers by changing the way the immune system works. Lymphoma and other cancers, including skin cancers, have happened in patients taking XELJANZ.
• The risks and benefits of treatment should be considered prior to initiating XELJANZ 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. Update immunizations in agreement with current immunization guidelines prior to initiating XELJANZ 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 get tears in their stomach or intestines. This happens most often in people who also take nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, or methotrexate. 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 should be used with caution in patients who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis).
• XELJANZ 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 and while they are taking XELJANZ, to check for these side effects. Normal cholesterol levels are important to good heart health. Healthcare providers may stop XELJANZ treatment because of changes in blood cell counts or liver test results.
• Use of XELJANZ 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 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.

• Patients should tell their healthcare providers if they plan to breastfeed or are breastfeeding. Patients and their healthcare provider should decide if they will take XELJANZ or breastfeed. They should not do both.
• In carriers of the hepatitis B or C virus (viruses that affect the liver), the virus may become active while using XELJANZ. Healthcare providers may do blood tests before and during treatment with XELJANZ.
• Common side effects include upper respiratory tract infections (common cold, sinus infections), headache, diarrhea, and nasal congestion, sore throat, and runny nose (nasopharyngitis).

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.

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 health care products. Our global portfolio includes medicines and vaccines as well as many of the world's best-known consumer health care 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. To learn more, please visit us at www.pfizer.com.

DISCLOSURE NOTICE: The information contained in this release is as of September 21, 2015. 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, including its potential benefits, and a potential indication for the treatment of adults with moderate to severe ulcerative colitis (the “Potential Indication”), 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 ability to meet anticipated trial commencement and completion dates and regulatory submission dates and the possibility of unfavorable clinical trial results, including unfavorable new clinical data and additional analyses of existing clinical data; whether and when any applications for the Potential Indication may be filed with regulatory authorities in any jurisdictions; whether and when regulatory authorities may approve such applications and or any other applications that are pending for XELJANZ, 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, including the Potential Indication; 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, 2014 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 SEC and available at www.sec.gov and www.pfizer.com.

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1 Loftus, E. Clinical Epidemiology of Inflammatory Bowel Disease: Incidence, Prevalence, and Environmental Influences.Gastroenterology 2004;126:1504–1517

2 Kappelman MD, et al. Recent Trends in the Prevalence of Crohn’s Disease and Ulcerative Colitis in a Commercially Insured US Population. Dig Dis Sci. 2013;58:519–525 [p519/col2/par1/ln1-2]

3 Molodecky NA, et al. Gastroenterol. 2012;142(1):46-54. 3. Langholz E. Ther Adv Gastroenterol. 2010;3(2):77-86.

4 Burisch J, et al. The burden of inflammatory bowel disease in Europe. Journal of Crohn’s and Colitis. 2013; 7:322-337

5 Louis E, Roughly A, Thakkar R, et. al. Impact of ulcerative colitis on patient quality of life in a real-world clinical setting. Presented at ECCO Congress 2013, Vienna, Austria. P180. https://www.ecco-ibd.eu/index.php/publications/congress-abstract-s/abstracts-2013/item/p180-impact-of-ulcerative-colitis-on-patient-quality-of-life-in-a-real-world-clinical-setting.html. [p1/results/ln7-9]

6 Landy J, Hart A.L. Commentary: short-term efficacy of tacrolimus in steroid-refractory ulcerative colitis. Alimentary Pharmacology Therapeutics. 2013 Feb. Available at http://www.ncbi.nlm.nih.gov/pubmed/23336680. Accessed August 8, 2015. [P493/Col1/Par1/Ln3-6]

7 Travis S P, Farrant J M, et al. Predicting outcome in severe ulcerative colitis. Gut 1996. Available athttp://www.ncbi.nlm.nih.gov/pubmed/8984031. Accessed August 8 2015. [P909/Col1/Par4/Ln 1-4]

8 Triantafillidis J, Merikas E, Georgopoulos F. Current and emerging drugs for the treatment of inflammatory bowel disease. Drug Design, Development and Therapy 2011. Available at http://www.researchgate.net/publication/51107773. Accessed August 11, 2015.

a. [P188/Col2/Par4/Ln2-6]
b. [P205/Col2/Par4]