NEW YORK--(BUSINESS WIRE)--
Pfizer Inc. (NYSE: PFE) announced today that the U.S. Food and Drug
Administration (FDA) has extended the action date by three months for
the supplemental New Drug Application (sNDA) for XELJANZ®
(tofacitinib), an oral treatment under investigation for adult patients
with moderately to severely active ulcerative colitis (UC).
The FDA determined that additional review time was necessary due to
information recently submitted by Pfizer and as such constitutes a major
amendment. The FDA has provided an anticipated Prescription Drug User
Fee Act (PDUFA) date in June 2018.
If approved by the FDA, tofacitinib would be the first oral Janus kinase
(JAK) inhibitor to be a therapeutic option for people living with
moderately to severely active UC.
About Tofacitinib
Tofacitinib citrate is a Janus kinase (JAK) inhibitor. Applications for
tofacitinib for the treatment of moderately to severely active UC are
currently under review by the U.S. FDA and the European Medicines Agency
(EMA). It is not currently approved for the treatment of UC.
As the developer of tofacitinib, Pfizer is a leader in JAK science and
is committed to 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
INDICATION
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.
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, 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 (e.g.,
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 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 rheumatoid
arthritis 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 5 mg 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.
Pfizer Inc.: Working together for a healthier world®
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to people that extend and significantly improve their lives. We strive
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DISCLOSURE NOTICE: The information contained in this release is as of
December 12, 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
(tofacitinib) and a potential new indication for the treatment of adult
patients with moderately to severely active ulcerative colitis (the
“potential indication”), 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; 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 potential indication or
any other potential indications for XELJANZ or XELJANZ XR may be filed
with regulatory authorities in any jurisdictions; whether and when the
FDA and EMA may approve the applications for XELJANZ for the potential
indication and 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 potential indication for XELJANZ; 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.
View source version on businesswire.com: http://www.businesswire.com/news/home/20171212006393/en/
Source: Pfizer Inc.