XELJANZ/XELJANZ XR, the First Oral JAK
Inhibitor in the U.S. for Adults with Moderate to Severe Rheumatoid
Arthritis, is now Approved for Adults with Active Psoriatic
Arthritis
Pfizer Inc. (NYSE:PFE) announced today that the United States
Food and Drug Administration (FDA) has approved XELJANZ® 5 mg twice
daily (BID) and XELJANZ® XR (tofacitinib) extended release 11 mg
once daily (QD) for the treatment of adult patients with active
psoriatic arthritis (PsA) who have had an inadequate response or
intolerance to methotrexate or other disease-modifying
antirheumatic drugs (DMARDs). XELJANZ/XELJANZ XR is the first and
only Janus kinase (JAK) inhibitor approved by the FDA for both
moderate to severe rheumatoid arthritis (RA) and active PsA.
“Psoriatic arthritis is a complex and progressive disease with
an unpredictable course,” said Angela Hwang, Global President,
Inflammation and Immunology, Pfizer. “The approval of XELJANZ is an
important step forward for patients seeking new treatments and is a
testament to Pfizer’s unwavering commitment to advancing patient
care.”
The recommended dose of XELJANZ/XELJANZ XR is in combination
with nonbiologic DMARDs, and use in combination with biologic
DMARDs or with potent immunosuppressants such as azathioprine and
cyclosporine is not recommended.
The FDA approval of XELJANZ for the treatment of adult patients
with active PsA was based on data from the Phase 3 Oral
Psoriatic Arthritis Trial (OPAL) clinical
development program, which consisted of two pivotal studies, OPAL
Broaden and OPAL Beyond, as well as available data from an ongoing
long-term extension trial, OPAL Balance. The findings from OPAL
Broaden and OPAL Beyond were published in October 2017 in the New
England Journal of Medicine.
Both pivotal studies met their two primary efficacy endpoints,
demonstrating statistically significant improvements in American
College of Rheumatology 20 (ACR20) response and change from
baseline in the Health Assessment Questionnaire–Disability Index
(HAQ-DI) score at three months in patients receiving XELJANZ 5 mg
BID treatment in combination with a nonbiologic DMARD, compared to
those treated with placebo. In OPAL Broaden, 50% of patients taking
XELJANZ 5 mg BID achieved an ACR20 response, compared to 33% of
patients taking placebo (p≤0.05), at three months. In OPAL Beyond,
50% of patients achieved an ACR20 response with XELJANZ 5 mg BID,
compared to 24% of patients taking placebo (p≤0.05), at three
months. In both studies, statistically significant improvements in
ACR20 response was also seen with XELJANZ 5 mg BID compared to
placebo at week 2, a secondary endpoint and the first post-baseline
assessment (OPAL Broaden: 22% and 6% [p=0.0003], respectively; OPAL
Beyond: 27% and 13% [p=0.0046], respectively).
“As a practicing rheumatologist, I’ve seen the significant
physical impact psoriatic arthritis has on people living with the
disease, and many patients are looking for additional therapeutic
options,” said Philip Mease, M.D., Swedish Medical Center,
University of Washington and study investigator. “I’m pleased that
XELJANZ is now available for use in the treatment of this chronic
condition.”
The safety profile observed in patients with active psoriatic
arthritis treated with XELJANZ was consistent with the safety
profile observed in rheumatoid arthritis patients. The most common
adverse events observed occurring in greater than 3% of patients on
XELJANZ 5 mg BID were nasopharyngitis, upper respiratory tract
infection, headache and diarrhea. Please see Important Safety
Information below.
“Psoriatic arthritis is a serious and debilitating chronic
illness that should be diagnosed and treated early,” said Randy
Beranek, president and CEO, National Psoriasis Foundation. “As an
organization that advocates for people living with psoriatic
arthritis, we welcome the availability of new therapies for
treating this disease.”
About the OPAL Clinical Development Program
OPAL Broaden was a 12-month study in adult patients with active
PsA who had an inadequate response to nonbiologic DMARDs and who
were tumor necrosis factor inhibitor (TNFi) naïve. The study
included an active control arm of adalimumab 40 mg administered
subcutaneously every two weeks; however, the study was not powered
for non-inferiority or superiority comparisons between tofacitinib
and adalimumab. OPAL Beyond was a six-month study of adult patients
with active PsA who had an inadequate response to a TNFi. All
patients had active PsA for at least six months based upon the
Classification Criteria for Psoriatic Arthritis (CASPAR), at least
three tender/painful joints and at least three swollen joints, and
active plaque psoriasis. In both studies, all patients were
required to receive a stable background dose of a single
nonbiologic DMARD.
About Psoriatic Arthritis
Psoriatic arthritis (PsA) is a chronic, autoimmune, inflammatory
disease that may include manifestations in peripheral joints,
tendons, ligaments or skin. PsA may include a variety of symptoms
such as joint pain and stiffness, swollen toes and/or fingers and
reduced range of motion.
About XELJANZ/XELJANZ XR (tofacitinib)
XELJANZ/XELJANZ XR is the first and only Janus kinase (JAK)
inhibitor approved by the FDA for moderate to severe rheumatoid
arthritis (RA) and is now approved for adults with active psoriatic
arthritis (PsA) who have had an inadequate response or intolerance
to methotrexate or other disease-modifying antirheumatic drugs
(DMARDs). As the developer of XELJANZ, Pfizer is committed to
advancing the science of JAK inhibition and enhancing understanding
of tofacitinib through robust clinical development programs in the
treatment of immune-mediated inflammatory conditions.
Please see full Prescribing Information for XELJANZ/XELJANZ XR
available at:
http://labeling.pfizer.com/showlabeling.aspx?id=959
INDICATIONS
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.
IMPORTANT SAFETY INFORMATION
BOXED WARNING: SERIOUS INFECTIONS AND MALIGNANCY
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 risks and benefits of treatment with XELJANZ/XELJANZ XR
should be carefully considered prior to initiating therapy in
patients with chronic or recurrent infection.
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.
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.
WARNINGS AND PRECAUTIONS
SERIOUS INFECTIONS
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. Consider the risks and benefits of
treatment before initiating XELJANZ/XELJANZ XR in patients:
• with chronic or recurrent infection;
• who have been exposed to tuberculosis (TB);
• with a history of a serious or an opportunistic infection;
• who have lived or traveled in areas of endemic TB or mycoses;
or
• with underlying conditions that may predispose them to
infection.
Patients should be closely monitored for the development of
signs and symptoms of infection during and after treatment with
XELJANZ/XELJANZ XR. XELJANZ/XELJANZ XR should be interrupted if a
patient develops a serious infection, an opportunistic infection,
or sepsis.
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.
Risk of infection may be higher with increasing degrees of
lymphopenia and consideration should be given to lymphocyte counts
when assessing individual patient risk of infection.
Tuberculosis
Evaluate and test patients for latent or active infection prior
to and per applicable guidelines during administration of
XELJANZ/XELJANZ XR. Consider anti-TB therapy prior to
administration of XELJANZ/XELJANZ XR in patients with a past
history of latent or active TB in whom an adequate course of
treatment cannot be confirmed, and for patients with a negative
test for latent TB but who have risk factors for TB infection.
Treat patients with latent TB with standard therapy before
administering XELJANZ/XELJANZ XR.
Viral Reactivation
Viral reactivation, including cases of herpes virus reactivation
(eg, herpes zoster), was observed in clinical studies with XELJANZ.
Screening for viral hepatitis should be performed in accordance
with clinical guidelines before starting therapy with
XELJANZ/XELJANZ XR. The risk of herpes zoster is increased in
patients treated with XELJANZ/XELJANZ XR and appears to be higher
in patients treated with XELJANZ in Japan and Korea.
MALIGNANCY and LYMPHOPROLIFERATIVE DISORDERS
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.
In the 7 controlled rheumatoid arthritis clinical studies, 11
solid cancers and 1 lymphoma were diagnosed in 3328 patients
receiving XELJANZ with or without DMARD, compared to 0 solid
cancers and 0 lymphomas in 809 patients in the placebo
with or without DMARD group during the first 12 months of exposure.
Lymphomas and solid cancers have also been observed in the
long-term extension studies in rheumatoid arthritis patients
treated with XELJANZ.
In the 2 controlled Phase 3 clinical trials in patients with
active psoriatic arthritis, there were 3 malignancies
(excluding NMSC) in 474 patients receiving XELJANZ plus nonbiologic
DMARD (6 to 12 months exposure) compared with 0 malignancies
in 236 patients in the placebo plus nonbiologic DMARD group (3
months exposure) and 0 malignancies in 106 patients in the
adalimumab plus nonbiologic DMARD group (12 months exposure). No
lymphomas were reported. Malignancies have also been observed in
the long-term extension study in psoriatic arthritis patients
treated with XELJANZ.
In Phase 2B controlled dose-ranging trials in de-novo renal
transplant patients, all of whom received induction therapy with
basiliximab, high-dose corticosteroids, and mycophenolic acid
products, Epstein Barr Virus-associated post-transplant
lymphoproliferative disorder was observed in 5 out of 218 patients
treated with XELJANZ (2.3%) compared to 0 out of 111 patients
treated with cyclosporine.
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.
Non-Melanoma Skin Cancer
Non-melanoma skin cancers (NMSCs) have been reported in patients
treated with XELJANZ. 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.
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).
LABORATORY ABNORMALITIES
Lymphocyte Abnormalities
Treatment with XELJANZ was associated with initial lymphocytosis
at 1 month of exposure followed by a gradual decrease in mean
lymphocyte counts of approximately 10% during 12 months of therapy.
Counts less than 500 cells/mm3 were associated with an increased
incidence of treated and serious infections. Avoid initiation of
XELJANZ/XELJANZ XR treatment in patients with a count less than 500
cells/mm3. In patients who develop a confirmed absolute lymphocyte
count less than 500 cells/mm3, treatment with XELJANZ/XELJANZ XR is
not recommended. Monitor lymphocyte counts at baseline and every
3 months thereafter.
Neutropenia
Treatment with XELJANZ was associated with an increased
incidence of neutropenia (less than 2000 cells/mm3) compared to
placebo. Avoid initiation of XELJANZ/XELJANZ XR treatment in
patients with an ANC less than 1000 cells/mm3. For patients who
develop a persistent ANC of 500-1000 cells/mm3, interrupt
XELJANZ/XELJANZ XR dosing until ANC is greater than or equal to
1000 cells/mm3. In patients who develop an ANC less than 500
cells/mm3, treatment with XELJANZ/XELJANZ XR is not recommended.
Monitor neutrophil counts at baseline and after 4-8 weeks of
treatment and every 3 months thereafter.
Anemia
Avoid initiation of XELJANZ/XELJANZ XR treatment in patients
with a hemoglobin level less than 9 g/dL. Treatment with
XELJANZ/XELJANZ XR should be interrupted in patients who develop
hemoglobin levels less than 8 g/dL or whose hemoglobin level drops
greater than 2 g/dL on treatment. Monitor hemoglobin at baseline
and after 4-8 weeks of treatment and every 3 months thereafter.
Liver Enzyme Elevations
Treatment with XELJANZ was associated with an increased
incidence of liver enzyme elevation compared to placebo. Most of
these abnormalities occurred in studies with background DMARD
(primarily methotrexate) therapy.
Routine monitoring of liver tests and prompt investigation of
the causes of liver enzyme elevations is recommended to identify
potential cases of drug-induced liver injury. If drug-induced liver
injury is suspected, the administration of XELJANZ/XELJANZ XR
should be interrupted until this diagnosis has been excluded.
Lipid Elevations
Treatment with XELJANZ was associated with increases in lipid
parameters, including total cholesterol, low-density lipoprotein
(LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol.
Maximum effects were generally observed within 6 weeks.
Assess lipid parameters approximately 4-8 weeks following
initiation of XELJANZ/XELJANZ XR therapy, and manage patients
according to clinical guidelines for the management of
hyperlipidemia.
VACCINATIONS
Avoid use of live vaccines concurrently with XELJANZ/XELJANZ XR.
The interval between live vaccinations and initiation of
tofacitinib therapy should be in accordance with current
vaccination guidelines regarding immunosuppressive agents. A
varicella virus naïve patient experienced dissemination of the
vaccine strain of varicella zoster virus 16 days after vaccination
with live attenuated virus vaccine which was 2 days after 5mg twice
daily treatment with tofacitinib. The patient recovered after
discontinuation of tofacitinib and treatment with antiviral
medication. Update immunizations in agreement with current
immunization guidelines prior to initiating XELJANZ/XELJANZ XR
therapy.
GENERAL
Specific to XELJANZ XR
Caution should be used when administering XELJANZ XR to patients
with pre-existing severe gastrointestinal narrowing. There have
been rare reports of obstructive symptoms in patients with known
strictures in association with the ingestion of other drugs
utilizing a non-deformable extended release formulation.
HEPATIC and RENAL IMPAIRMENT
Use of XELJANZ/XELJANZ XR in patients with severe hepatic
impairment is not recommended.
The recommended dose in patients with moderate hepatic
impairment or with moderate or severe renal impairment is XELJANZ 5
mg once daily.
ADVERSE REACTIONS
The most common serious adverse reactions were serious
infections. The most commonly reported adverse reactions during the
first 3 months in controlled clinical trials with XELJANZ 5 mg
twice daily and placebo, respectively, (occurring in greater than
or equal to 2% of patients treated with XELJANZ with or without
DMARDs) were upper respiratory tract infections (4.5%, 3.3%),
headache (4.3%, 2.1%), diarrhea (4.0%, 2.3%), and nasopharyngitis
(3.8%, 2.8%).
USE IN PREGNANCY
There are no adequate and well-controlled studies in pregnant
women and the estimated background risks of major birth defects and
miscarriage for the indicated population is unknown. Based on
animal studies, tofacitinib has the potential to affect a
developing fetus. Women of reproductive potential should be advised
to use effective contraception.
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DISCLOSURE NOTICE: The information contained in this
release is as of December 14, 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 XELJANZ
and XELJANZ XR and a new indication 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, including their 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, without limitation, 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, including in the new
indication; the risk that clinical trial data are subject to
differing interpretations, and, even when we view data as
sufficient to support the safety and/or effectiveness of a product
candidate, regulatory authorities may not share our views and may
require additional data or may deny approval altogether; whether
regulatory authorities will be satisfied with the design of and
results from our clinical studies; whether and when any other
applications for the new indication or any other potential
indications for XELJANZ or XELJANZ XR may be filed with regulatory
authorities in any jurisdictions; whether and when regulatory
authorities in any jurisdictions may approve any other applications
that may be filed or pending 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 new 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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Pfizer Inc.Media:Neha Wadhwa,
212-733-2835Neha.Wadhwa@pfizer.comorInvestors:Chuck Triano,
212-733-3901Charles.E.Triano@pfizer.com
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