Phase 3 OCTAVE Studies of Oral Tofacitinib in Ulcerative Colitis Results Published in The New England Journal of Medicine

NEW YORK–(BUSINESS WIRE)– Pfizer Inc. (NYSE:PFE) announced today that detailed results from the
Phase 3 Oral Clinical Trials for tofAcitinib
in ulceratiVE colitis (OCTAVE) clinical program were published in The
New England Journal of Medicine (NEJM).

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Data from all three pivotal Phase 3 studies – OCTAVE Induction 1, OCTAVE
Induction 2 and OCTAVE Sustain – met their respective primary endpoints,
demonstrating that tofacitinib citrate was more effective than placebo
in inducing and maintaining remission in patients with moderate to
severe ulcerative colitis (UC).^1a,1b Remission was defined as
a Mayo score* of 2 points or lower, with no individual subscore
exceeding 1 point, and a rectal bleeding subscore of 0.^1c

“The publication of results from the full Phase 3 OCTAVE clinical
program is a significant milestone,” said William J. Sandborn, MD,
Chief, Division of Gastroenterology, Professor of Medicine at the
University of California San Diego School of Medicine and study
investigator. “This robust data set provides evidence that tofacitinib,
if approved, could be an important new oral treatment option with the
potential to help patients with moderate to severe active ulcerative
colitis achieve and maintain remission.”

OCTAVE Induction 1 & 2

OCTAVE Induction 1 and OCTAVE Induction 2 each evaluated induction of
remission by oral tofacitinib 10 mg twice-daily (BID) compared to
placebo in adult patients with moderate to severe UC.^1d The
studies enrolled 598 and 541 patients, respectively.^1d
Eligible patients were randomly assigned to receive eight weeks of
therapy with oral tofacitinib 10 mg BID (476 and 429 patients,
respectively) or placebo (122 and 112 patients, respectively).^1e,1f

In OCTAVE Induction 1, a statistically significant and greater
proportion of patients receiving tofacitinib 10 mg BID (18.5%) were in
remission at Week 8, compared to 8.2% receiving placebo (p=0.007).^1g
Similar results were observed in OCTAVE Induction 2, with 16.6% of
patients receiving tofacitinib 10 mg BID achieving remission at Week 8,
compared to 3.6% receiving placebo (p<0.001).^1h

In addition, across each study, a statistically significant and greater
proportion of patients receiving tofacitinib 10 mg BID achieved the key
secondary endpoint of mucosal healing at Week 8, including 31.3% of
patients compared to 15.6% receiving placebo in OCTAVE Induction 1, and
28.4% of patients compared to 11.6% receiving placebo in OCTAVE
Induction 2 (p<0.001 across both studies).^1i,1j

OCTAVE Sustain

The OCTAVE Sustain study evaluated the efficacy of tofacitinib as
maintenance therapy compared to placebo in adult patients with moderate
to severe UC.^1k It included patients who had completed one of
the OCTAVE Induction studies and had achieved at least clinical response
(≥3 points reduction and ≥30% decrease from baseline Mayo score plus a
decrease in rectal bleeding subscore of ≥1 or absolute rectal bleeding
subscore ≤1).^1l A total of 593 participants were randomized
to receive maintenance treatment with tofacitinib 5 mg BID (198
patients), tofacitinib 10 mg BID (197 patients) or placebo (198
patients) for 52 weeks.^1m

In OCTAVE Sustain, 34.3% and 40.6% of patients achieved remission at
Week 52 with tofacitinib 5 mg BID and tofacitinib 10 mg BID,
respectively, compared to 11.1% taking placebo (p<0.001).¹ⁿ
In addition, both doses of tofacitinib met the key secondary endpoints
of the study, mucosal healing and sustained steroid-free remission among
baseline remitters.^1o Across tofacitinib 5 mg BID,
tofacitinib 10 mg BID and placebo arms, mucosal healing was achieved by
37.4%, 45.7% and 13.1% of patients (p<0.001), respectively, and
sustained steroid-free remission was achieved by 35.4%, 47.3% and 5.1%
(p<0.001), respectively.^1o

“Ulcerative colitis is a debilitating disease that affects all aspects
of patients’ lives. We are pleased to share the results of this
promising clinical trial of tofacitinib as part of our efforts to
improve the lives of patients through our research with Janus kinase
inhibitors, » said Michael Corbo, PhD, Chief Development Officer,
Inflammation & Immunology, Global Product Development, Pfizer, Inc. « If
approved for this indication, tofacitinib could potentially be an
important new oral treatment option for people living with UC.”

During the OCTAVE Induction studies, overall infection and serious
infection rates were higher with tofacitinib than placebo.^1p
In OCTAVE Induction 1, 23.3% and 1.3% of patients receiving tofacitinib
10 mg BID had infections and serious infections, respectively, compared
to 15.6% and 0 receiving placebo.^1p In OCTAVE Induction 2,
18.2% and 0.2% of patients receiving tofacitinib 10 mg BID had
infections and serious infections, respectively, compared to 15.2% and 0
receiving placebo.^1p

During OCTAVE Sustain, serious infection rates were similar across
treatment groups (1.0%, 0.5% and 1.0% across tofacitinib 5 mg BID, 10 mg
BID and placebo groups, respectively).^1q Overall infection
rates were higher with tofacitinib than placebo (35.9%, 39.8% and 24.2%
across tofacitinib 5 mg BID, 10 mg BID and placebo groups,
respectively). Cases of herpes zoster were more frequently observed with
tofacitinib 10 mg BID compared to other treatment groups (1.5%, 5.1% and
0.5% across tofacitinib 5 mg BID, 10 mg BID and placebo groups,
respectively).^1q

Across all studies, five tofacitinib-treated patients had adjudicated
non-melanoma skin cancer, five had adjudicated cardiovascular events and
there were increases in lipids with tofacitinib.^1r,1s,1t,1u
There were two cases of malignancy in the control groups limited to one
case of non-melanoma skin cancer and one case of invasive ductal breast
carcinoma during OCTAVE Sustain.^1t

The manuscript of full study results, which indicate that tofacitinib
citrate was more effective than placebo in inducing and maintaining
remission in patients with moderate to severe active UC, is available at http://www.nejm.org/doi/full/10.1056/NEJMoa1606910.

About Ulcerative Colitis

UC is a chronic, often debilitating inflammatory bowel disease that
affects millions of people worldwide.^2,3 While the exact
cause of UC is unknown, it is believed that UC is the result of complex
interactions between multiple factors that include genetic
predisposition and an exaggerated immune response to a microbial trigger.⁴
It can cause chronic diarrhea with blood and mucus, abdominal pain and
cramping, fever and weight loss.⁵ UC can have a significant
effect on work, family and social activities.⁶ In up to
one-third of patients with UC, treatment is not completely successful or
complications may arise.⁷ Under these circumstances, surgery
to remove the colon (colectomy) may be considered.⁷

About XELJANZ^® (tofacitinib citrate)

XELJANZ^® (tofacitinib citrate) is a prescription
medicine called a Janus kinase (JAK) inhibitor. XELJANZ is approved in
more than 80 countries around the world for the treatment of moderately
to severely active rheumatoid arthritis (RA). XELJANZ is being
investigated for the treatment of moderate to severe UC and is not
currently approved for this indication.

As the developer of XELJANZ, Pfizer is a leader in JAK innovation.
Pfizer is committed to advancing the science of JAK inhibition and
enhancing understanding of XELJANZ through robust clinical development
programs in the treatment of immune-mediated inflammatory conditions.

XELJANZ/XELJANZ XR U.S. Label Information

XELJANZ (tofacitinib citrate)/XELJANZ XR (tofacitinib citrate)
extended-release 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.

• 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/XELJANZ XR 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/XELJANZ XR.
  Healthcare providers may do blood tests before and during treatment
  with XELJANZ/XELJANZ XR.
• 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/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,
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DISCLOSURE NOTICE: The information contained in this release is as of
May 3, 2017. 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
new indication for XELJANZ for the treatment of adult patients with
moderate to severe active UC (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 ability to meet anticipated trial
commencement and completion dates and regulatory submission dates, as
well as the possibility of unfavorable clinical trial results, including
unfavorable new clinical data and additional analyses of existing
clinical data; uncertainties regarding the commercial success of XELJANZ
and XELJANZ XR; whether and when any applications for the potential
indication may be filed with regulatory authorities in any
jurisdictions; whether and when regulatory authorities in any
jurisdictions may approve such applications and/or any other
applications that are pending or may be filed for XELJANZ or XELJANZ XR,
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, 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, 2016 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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