Pfizer : Announces Initiation of Phase 3 Trial of Tofacitinib in Patients with Ankylosing Spondylitis

For immediate release: October 18, 2018

Media Contact: Neha Wadhwa M: [phone]

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Investor Contact: Ryan Crowe O: [phone]

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Pfizer Announces Initiation of Phase 3 Trial of Tofacitinib in

Patients with Ankylosing Spondylitis

NEW YORK, N.Y., October 18, 2018-Pfizer Inc. (NYSE:PFE) announced today the initiation ofNCT03502616, a Phase 3, randomized, double-blind, placebo-controlled, investigational study evaluating the efficacy and safety of tofacitinib 5 mg twice daily (BID), an oral Janus kinase (JAK) inhibitor, versus placebo in adult patients with active ankylosing spondylitis (AS). This study, now open for enrollment, is being conducted in adult patients who have had an inadequate response or who have been intolerant to a nonsteroidal anti-inflammatory drug (NSAID) therapy.1Tofacitinib is not FDA approved for the treatment of adults with ankylosing spondylitis (AS) and its safety and efficacy has not been established in AS.

"Ankylosing spondylitis is often progressive and can lead to loss of mobility for some patients,"said Michael Corbo, Chief Development Officer, Inflammation & Immunology, Pfizer Global Product Development."We are proud to initiate our Phase 3 study to evaluate tofacitinib in ankylosing spondylitis, given the significant need for additional treatment options for people living with this debilitating condition."

About the Study

The primary endpoint of the study is the proportion of patients achieving 20 percent improvement in Assessment in SpondyloArthritis

International Society (ASAS20) response criteria at Week 16.1The trialwill run for a total of 48 weeks.1For more information about the study, please visitClinicalTrials.gov.

About Ankylosing Spondylitis

Ankylosing spondylitis (AS) is a form of chronic inflammatory arthritis that affects the axial skeleton, including the sacroiliac joint and the spine. Approximately 50 percent of AS patients have other joint involvement, including peripheral arthritis and enthesitis.2,3

About XELJANZ®(tofacitinib)

XELJANZ®(tofacitinib) is approved in the U.S. for adult patients in three indications: moderately to severely active rheumatoid arthritis

(RA), active psoriatic arthritis (PsA) and moderately to severely active ulcerative colitis (UC).4As a pioneer in JAK science, we are continuing to advance our research and development of JAK inhibition through robust clinical programs.

The JAK pathways are believed to play an important role in inflammatory processes as they are involved in signaling for over 50 cytokines and growth factors, many of which drive immune-mediated conditions.5,6

INDICATIONS and IMPORTANT SAFETY INFORMATION

Rheumatoid Arthritis

• •XELJANZ/XELJANZ XR (tofacitinib) is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate. It may be used as monotherapy or in combination with methotrexate or other nonbiologic disease-modifying antirheumatic drugs (DMARDs).

• •Limitations of Use: Use of XELJANZ/XELJANZ XR in combination with biologic DMARDs or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended.

Psoriatic Arthritis

• •XELJANZ/XELJANZ XR (tofacitinib) is indicated for the treatment of adult patients with active psoriatic arthritis who have had an inadequate response or intolerance to methotrexate or other disease-modifying antirheumatic drugs (DMARDs).

• •Limitations of Use: Use of XELJANZ/XELJANZ XR in combination with biologic DMARDs or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended.

Ulcerative Colitis

• •XELJANZ (tofacitinib) is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis (UC).

• •Limitations of Use: Use of XELJANZ in combination with biologic therapies for UC or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended.

SERIOUS INFECTIONS

Patients treated with XELJANZ/XELJANZ XR are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants, such as methotrexate or corticosteroids.

If a serious infection develops, interrupt XELJANZ/XELJANZ XR until the infection is controlled.

Reported infections include:

• •Active tuberculosis, which may present with pulmonary or extrapulmonary disease. Patients should be tested for latent tuberculosis before XELJANZ/XELJANZ XR use and during therapy. Treatment for latent infection should be initiated prior to XELJANZ/XELJANZ XR use.

• •Invasive fungal infections, including cryptococcosis and pneumocystosis. Patients with invasive fungal infections may present with disseminated, rather than localized, disease.

• •Bacterial, viral, including herpes zoster, and other infections due to opportunistic pathogens.

The most common serious infections reported with XELJANZ included pneumonia, cellulitis, herpes zoster, urinary tract infection, diverticulitis, and appendicitis. Avoid use of XELJANZ/XELJANZ XR in patients with an active, serious infection, including localized infections, or with chronic or recurrent infection.

In the UC population, XELJANZ 10 mg twice daily was associated with greater risk of serious infections compared to 5 mg twice daily. Opportunistic herpes zoster infections (including meningoencephalitis, ophthalmologic, and disseminated cutaneous) were seen in patients who were treated with XELJANZ 10 mg twice daily.

The risks and benefits of treatment with XELJANZ/XELJANZ XR should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection,or those who have lived or traveled in areas of endemic TB or mycoses. Screening for viral hepatitis should be performed in accordance with clinical guidelines before starting therapy.

Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with XELJANZ/XELJANZ XR, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy.

Caution is also recommended in patients with a history of chronic lung disease, or in those who develop interstitial lung disease, as they may be more prone to infection.

MALIGNANCIES

Lymphoma and other malignancies have been observed in patients treated with XELJANZ. Epstein Barr Virus-associated post-transplant lymphoproliferative disorder has been observed at an increased rate in renal transplant patients treated with XELJANZ and concomitant immunosuppressive medications.

Consider the risks and benefits of XELJANZ/XELJANZ XR treatment prior to initiating therapy in patients with a known malignancy other than a successfully treated non-melanoma skin cancer (NMSC) or when considering continuing XELJANZ/XELJANZ XR in patients who develop a malignancy.

Malignancies (including solid cancers and lymphomas) were observed more often in patients treated with XELJANZ 10 mg twice daily dosing in the UC long-term extension study.

Other malignancies were observed in clinical studies and the post-marketing setting including, but not limited to, lung cancer, breast cancer, melanoma, prostate cancer, and pancreatic cancer. NMSC have been reported in patients treated with XELJANZ. In the UC population, treatment with XELJANZ 10 mg twice daily was associated with greater risk of NMSC. Periodic skin examination is recommended for patients who are at increased risk for skin cancer.

GASTROINTESTINAL PERFORATIONS

Gastrointestinal perforations have been reported in XELJANZ clinical trials, although the role of JAK inhibition is not known. In these studies, many patients with rheumatoid arthritis were receiving background therapy with Nonsteroidal Anti-Inflammatory Drugs (NSAIDs).