- CHMP also recommends XELJANZ® (tofacitinib) approval for the
treatment of adults with active ankylosing spondylitis
Pfizer Inc. (NYSE: PFE) today announced that the European
Medicines Agency's (EMA) Committee for Medicinal Products for Human
Use (CHMP) has adopted a positive opinion recommending the 100 mg
and 200 mg doses of abrocitinib, an oral, once-daily, Janus kinase
1 (JAK1) inhibitor, for marketing authorization to treat moderate
to severe atopic dermatitis (AD) in adults who are candidates for
systemic therapy. The CHMP also adopted a positive opinion
recommending marketing authorization for XELJANZ® (tofacitinib) 5
mg and 10 mg, administered twice daily, for the treatment of adults
with active ankylosing spondylitis (AS) who have responded
inadequately to conventional therapy.
“The CHMP’s positive recommendation brings us closer to our goal
of helping people living with moderate to severe atopic dermatitis
in Europe find relief,” said Michael Corbo, PhD, Chief Development
Officer, Inflammation & Immunology, Pfizer Global Product
Development. “We look forward to working with the European
Commission and hope to soon provide abrocitinib to people in Europe
and eventually to more people worldwide who are living with this
debilitating disease, many of whom have limited treatment options
today.”
“Atopic dermatitis can be a debilitating condition that impacts
the daily lives of millions of people,” said Dr. Diamant Thaci,
Comprehensive Center for Inflammation Medicine, University of
Luebeck, Germany. “Abrocitinib has shown significant efficacy,
including relief from the hallmark chronic itch, rapid improvements
in skin clearance, extent and severity of disease versus placebo,
and a favorable risk-benefit profile. If approved, abrocitinib may
become an important new treatment option for patients living with
moderate to severe atopic dermatitis.”
Based on these CHMP recommendations, a decision by the European
Commission, which authorizes marketing approval in the European
Union, is expected on the abrocitinib and XELJANZ applications
later this year. If granted by the European Commission, the
centralized marketing authorizations would be valid in all EU
Member States as well as in Iceland, Liechtenstein, and Norway.
The recommendation for abrocitinib is based on the results of
five Phase 3 studies and a long-term extension study from a robust
clinical trial program including more than 3,100 patients.
The recommendation for XELJANZ is based on data from a Phase 3,
multicenter, randomized, double-blind, placebo-controlled study
that evaluated the efficacy and safety of XELJANZ twice daily
versus placebo in 269 adult patients living with active AS.
About Abrocitinib Abrocitinib is an oral small molecule
that selectively inhibits Janus kinase (JAK) 1. Inhibition of JAK1
is thought to modulate multiple cytokines involved in
pathophysiology of atopic dermatitis, including interleukin IL-4,
IL-13, IL-31, IL-22, and thymic stromal lymphopoietin (TSLP).
CIBINQO® (abrocitinib) received marketing authorization from the
UK Medicines and Healthcare products Regulatory Agency (MHRA) and
the Japanese Ministry of Health, Labour and Welfare (MHLW) in
September 2021.
About XELJANZ XELJANZ is approved in the European Union
in four indications: adults with moderately to severely active
rheumatoid arthritis (RA) after disease modifying antirheumatic
drug (DMARD) failure or intolerance, adults with active psoriatic
arthritis (PsA) after DMARD failure or intolerance, adults with
moderately to severely active ulcerative colitis (UC) who have had
an inadequate response, lost response, or were intolerant to either
conventional therapy or a biologic agent, and active polyarticular
juvenile idiopathic arthritis (JIA) and juvenile PsA in patients
two years of age and older who have responded inadequately to
previous therapy with DMARDs. Limitations of Use below.
XELJANZ has been studied in more than 50 clinical trials
worldwide and prescribed to more than 300,000 adult patients (the
majority of whom were RA patients) worldwide since 2012.i,ii.
In June 2021, the Committee for Medicine Products for Human Use
of the European Medicines Agency adopted a recommendation from the
Pharmacovigilance Risk Assessment Committee (PRAC) following its
review of XELJANZ in the European Union, which states that in
patients over 65 years of age, patients who are current or past
smokers, patients with other cardiovascular (CV) risk factors, and
patients with other malignancy risk factors, XELJANZ should only be
used if no suitable treatment alternatives are available. The
CHMP-endorsed PRAC recommendation is applicable to all EU member
states and has been implemented in the XELJANZ summary of product
characteristics.
Pfizer is also continuing to work with the U.S. Food and Drug
Administration (FDA) and other regulatory agencies to review the
full results and analysis of the ORAL Surveillance data. Most
recently in September 2021, the FDA issued a Drug Safety
Communication (DSC) related to XELJANZ®/XELJANZ XR® and two other
arthritis medicines in the same drug class, based on its completed
review of the ORAL Surveillance trial.
About Atopic Dermatitis AD is a chronic skin disease
characterized by inflammation of the skin and skin barrier
defects.iii,iv Lesions of AD are characterized by erythema (skin
turning red or purple depending on normal skin color), itching,
induration (hardening)/papulation (formulation of papules), and
oozing/crusting.iii,iv
AD affects up to 10% of adults worldwide.v The prevalence of AD
in adults in the European Union is approximately 5-10%.vi,vii
About Ankylosing Spondylitis AS is a chronic,
inflammatory disease that affects men and women in early adulthood.
The first symptoms usually occur before the age of 30 and seldom
onset after the age of 45.viii,ix Symptoms of AS include pain and
stiffness in the back and hips. Over time, some patients may
experience fusion of the vertebrae in the spinal column.ix AS can
cause severe, chronic pain for those living with the disease and
can negatively impact health-related quality of life.ix An
estimated average of 0.19% of adults in the European Union live
with AS.x
FDA-APPROVED 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.
- 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 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/XELJANZ XR is indicated for the treatment of adult
patients with moderately to severely active ulcerative colitis
(UC), who have had an inadequate response or who are intolerant to
TNF blockers.
- Limitations of Use: Use of XELJANZ in combination with
biological therapies for UC or with potent immunosuppressants such
as azathioprine and cyclosporine is not recommended.
Polyarticular Course Juvenile Idiopathic Arthritis
- XELJANZ/XELJANZ Oral Solution is indicated for the treatment of
active polyarticular course juvenile idiopathic arthritis (pcJIA)
in patients 2 years of age and older.
- Limitations of Use: Use of XELJANZ/XELJANZ Oral Solution in
combination with biologic DMARDs or potent immunosuppressants such
as azathioprine and cyclosporine is not recommended.
IMPORTANT SAFETY INFORMATION
SERIOUS INFECTIONS Patients treated with XELJANZ* 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 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 use and during therapy. Treatment for
latent infection should be initiated prior to XELJANZ 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
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 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. Viral reactivation
including herpes virus and hepatitis B reactivation have been
reported. 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, 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.
MORTALITY Rheumatoid arthritis (RA) patients 50 years of age
and older with at least one cardiovascular (CV) risk factor treated
with XELJANZ 10 mg twice a day had a higher rate of all-cause
mortality, including sudden CV death, compared to those treated
with XELJANZ 5 mg given twice daily or TNF blockers in a large,
ongoing, postmarketing safety study. XELJANZ 10 mg twice daily
or XELJANZ XR 22 mg once daily is not recommended for the treatment
of RA or PsA. For UC, use XELJANZ at the lowest effective dose and
for the shortest duration needed to achieve/maintain therapeutic
response.
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 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 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.
NMSCs 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.
THROMBOSIS Thrombosis, including pulmonary embolism, deep
venous thrombosis, and arterial thrombosis, have occurred in
patients treated with XELJANZ and other Janus kinase inhibitors
used to treat inflammatory conditions. RA patients who were 50
years of age and older with at least one CV risk factor treated
with XELJANZ 10 mg twice daily compared to XELJANZ 5 mg twice daily
or TNF blockers in a large, ongoing postmarketing safety study had
an observed increase in incidence of these events. Many of these
events were serious and some resulted in death. Avoid XELJANZ in
patients at risk. Discontinue XELJANZ and promptly evaluate
patients with symptoms of thrombosis. For patients with UC, use
XELJANZ at the lowest effective dose and for the shortest duration
needed to achieve/maintain therapeutic response. XELJANZ 10 mg
twice daily or XELJANZ XR 22 mg once daily is not recommended for
the treatment of RA or PsA. In a long-term extension study in UC,
four cases of pulmonary embolism were reported in patients taking
XELJANZ 10 mg twice daily, including one death in a patient with
advanced 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). There
was no discernable difference in frequency of gastrointestinal
perforation between the placebo and the XELJANZ arms in clinical
trials of patients with UC, and many of them were receiving
background corticosteroids. 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 or
taking NSAIDs).
HYPERSENSITIVITY Angioedema and urticaria that may
reflect drug hypersensitivity have been observed in patients
receiving XELJANZ and some events were serious. If a serious
hypersensitivity reaction occurs, promptly discontinue tofacitinib
while evaluating the potential cause or causes of the reaction.
LABORATORY ABNORMALITIES Lymphocyte Abnormalities:
Treatment with XELJANZ was associated with initial lymphocytosis at
one month of exposure followed by a gradual decrease in mean
lymphocyte counts. Avoid initiation of XELJANZ 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 is not recommended. 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. 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 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
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 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 treatment in patients
with a hemoglobin level less than 9 g/dL. Treatment with XELJANZ
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. If
drug-induced liver injury is suspected, the administration of
XELJANZ should be interrupted until this diagnosis has been
excluded. 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.
Lipid Elevations: Treatment with XELJANZ was associated
with dose-dependent 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. There were no clinically
relevant changes in LDL/HDL cholesterol ratios. Manage patients
with hyperlipidemia according to clinical guidelines. Assessment of
lipid parameters should be performed approximately 4-8 weeks
following initiation of XELJANZ therapy.
VACCINATIONS Avoid use of live vaccines concurrently with
XELJANZ. The interval between live vaccinations and initiation of
tofacitinib therapy should be in accordance with current
vaccination guidelines regarding immunosuppressive agents. Update
immunizations in agreement with current immunization guidelines
prior to initiating XELJANZ therapy.
PATIENTS WITH GASTROINTESTINAL NARROWING 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 in patients
with severe hepatic impairment is not recommended.
For patients with moderate hepatic impairment or with moderate
or severe renal impairment taking XELJANZ 5 mg twice daily, reduce
to XELJANZ 5 mg once daily.
For UC patients with moderate hepatic impairment or with
moderate or severe renal impairment taking XELJANZ 10 mg twice
daily, reduce to XELJANZ 5 mg twice 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 in patients with RA 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 infection, nasopharyngitis, diarrhea, headache,
and hypertension. The safety profile observed in patients with
active PsA treated with XELJANZ was consistent with the safety
profile observed in RA patients.
Adverse reactions reported in ≥5% of patients treated with
either 5 mg or 10 mg twice daily of XELJANZ and ≥1% greater than
reported in patients receiving placebo in either the induction or
maintenance clinical trials for UC were: nasopharyngitis, elevated
cholesterol levels, headache, upper respiratory tract infection,
increased blood creatine phosphokinase, rash, diarrhea, and herpes
zoster.
USE IN PREGNANCY Available data with XELJANZ use in
pregnant women are insufficient to establish a drug associated risk
of major birth defects, miscarriage or adverse maternal or fetal
outcomes. There are risks to the mother and the fetus associated
with rheumatoid arthritis and UC in pregnancy. In animal studies,
tofacitinib at 6.3 times the maximum recommended dose of 10 mg
twice daily demonstrated adverse embryo-fetal findings. The
relevance of these findings to women of childbearing potential is
uncertain. Consider pregnancy planning and prevention for females
of reproductive potential.
* Unless otherwise stated, “XELJANZ” in the Important Safety
Information refers to XELJANZ, XELJANZ XR, and XELJANZ Oral
Solution.
Please see full Prescribing Information, including BOXED WARNING
for XELJANZ available at: www.xeljanzpi.com.
About Pfizer: Breakthroughs That Change Patients’ Lives
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, including innovative medicines and vaccines. 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 170 years, we have worked to make a difference for all
who rely on us. We routinely post information that may be important
to investors on our website at www.Pfizer.com. In addition, to
learn more, please visit us on www.Pfizer.com and follow us on
Twitter at @Pfizer and @Pfizer News, LinkedIn, YouTube and like us
on Facebook at Facebook.com/Pfizer.
Disclosure Notice The information contained in this
release is as of October 15, 2021. 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
product candidate, abrocitinib, and XELJANZ (tofacitinib),
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 the
ability to meet anticipated clinical endpoints, commencement and/or
completion dates for our clinical trials, regulatory submission
dates, regulatory approval dates and/or launch dates, as well as
the possibility of unfavorable new clinical data and further
analyses of existing clinical data; the risk that clinical trial
data are subject to differing interpretations and assessments by
regulatory authorities; whether regulatory authorities will be
satisfied with the design of and results from our clinical studies;
whether and when drug applications may be filed in any other
jurisdictions for any potential indication for abrocitinib or
XELJANZ; whether and when the applications for abrocitinib and
XELJANZ pending with the U.S. Food and Drug Administration (FDA)
and European Medicines Agency may be approved and whether and when
any such other applications that may be pending or filed for
abrocitinib or XELJANZ may be approved by regulatory authorities,
which will depend on myriad factors, including making a
determination as to whether the product's benefits outweigh its
known risks and determination of the product's efficacy and, if
approved, whether abrocitinib or XELJANZ will be commercially
successful; decisions by regulatory authorities impacting labeling,
manufacturing processes, safety and/or other matters that could
affect the availability or commercial potential of abrocitinib or
XELJANZ; uncertainties regarding the commercial or other impact of
the results of clinical trial A3921133 (ORAL Surveillance) or any
other Janus kinase (JAK) inhibitor studies and data, the FDA’s drug
safety communication, the CHMP-endorsed PRAC recommendation and any
potential actions by regulatory authorities based on analysis of
such studies and data, including on other JAK inhibitors in our
portfolio, which will depend, in part, on benefit-risk assessments
and labeling determinations; uncertainties regarding the impact of
COVID-19 on our business, operations, and financial results; 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, 2020 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.
i ClinicalTrials.gov. Tofacitinib RA Studies. Accessed September
2021.
https://clinicaltrials.gov/ct2/results?term=tofacitinib%2C+rheumatoid+arthritis%2C+ORAL&type=&rslt=&recr=&age_v=&gndr=&cond=Rheumatoid+Arthritis&intr=&titles=&outc=&spons=&lead=&id=&state1=&cntry1=&state2=&cntry2=&state3=&cntry3=&locn=&rcv_s=&rcv_e=&lup_s=&lup_e=
ii Pfizer. Data on File. June 2021. iii Hanifin JM, Reed ML. A
population-based survey of eczema in the United States. Dermatitis.
2007;18(2):82-91. iv Bieber T. Atopic dermatitis. Dermatology.
2012;1(3):203-217. v Oszukowska M, Michalak I, Gutfreund K, et al.
Role of primary and secondary prevention in atopic dermatitis.
Postep Derm Alergol. 2015:32(6):409-420. vi J. Silverberg, A.
Wollenberg, A. Egeberg, et al. Worldwide prevalence and severity of
Atopic Dermatitis. Poster presented at EADV 2018 Annual Meeting.
Paris, France. vii Barbarot S, Auziere S, Gadkari A, et al.
Epidemiology of atopic dermatitis in adults: Results from an
international survey. Allergy. 2018;73(6):1284-1293.
doi:10.1111/all.13401. viii Exarchou S, Lindstr�m U, Askling J, et
al. The prevalence of clinically diagnosed ankylosing spondylitis
and its clinical manifestations: a nationwide register study.
Arthritis Res Ther. 2015;17(1):118. Published 2015 May 9.
doi:10.1186/s13075-015-0627-0 ix University of Maryland Medical
Center. A Patient’s Guide to AS. Available at:
https://www.umms.org/ummc/health-services/orthopedics/services/spine/patient-guides/ankylosing-spondylitis
x Dean LE, Jones GT, MacDonald AG, Downham C, Sturrock RD,
Macfarlane GJ. Global prevalence of ankylosing spondylitis.
Rheumatology (Oxford). 2014 Apr;53(4):650-7. doi:
10.1093/rheumatology/ket387. Epub 2013 Dec 9. PMID: 24324212.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20211015005319/en/
Media Relations: +1 (212) 733-1226 EUPress@Pfizer.com
Investor Relations: +1 (212) 733-4848 IR@Pfizer.com
Pfizer (NYSE:PFE)
Gráfico Histórico do Ativo
De Mar 2024 até Abr 2024
Pfizer (NYSE:PFE)
Gráfico Histórico do Ativo
De Abr 2023 até Abr 2024