CIMZIA® (certolizumab pegol) Label Change Marks Important Advance for European Women of Childbearing Age With Chronic Rheumatic Disease

Brussels (ots/PRNewswire) -

- European Medicines Agency (EMA) has approved label change for UCB's
CIMZIA® (certolizumab pegol), making it the first anti-TNF for
potential use in women with chronic rheumatic disease, during both
pregnancy and breastfeeding
- Data submitted to regulatory authorities included
first-of-their-kind clinical studies demonstrating minimal transfer
of CIMZIA through the placenta and breast milk from mother to
infant[1],[2]
- Adequate disease control is crucial in women of childbearing age to
ensure optimal infant and maternal health and to reduce adverse
pregnancy outcomes

UCB today announced that the European Medicines Agency (EMA)
approved a label change for CIMZIA® (certolizumab pegol), making it
the first anti-TNF treatment option that could be considered for
women with chronic rheumatic disease, during both pregnancy and
breastfeeding.

"Women of childbearing age with chronic rheumatic disease are a
patient population in need of reliable treatment options and
guidance. Women frequently discontinue their anti-TNF treatment
throughout pregnancy, a time when disease control is essential to
ensure optimal infant and maternal health. CIMZIA is the only
available anti-TNF treatment that is clinically proven to show
minimal placental transfer from mother to infant during pregnancy,"
said Xavier Mariette, MD, PhD, Head of Rheumatology, Bicetre
Hospital, Paris-Sud University.

"Today's label change for CIMZIA is important for many European
women who need treatment options to manage their chronic rheumatic
disease without compromising their plans for pregnancy and
breastfeeding," said Emmanuel Caeymaex, Head of Immunology and
Executive Vice President, Immunology Patient Value Unit, UCB. "UCB is
executing on its Patient Value Strategy to connect the unmet needs of
patients with innovative science. The research we conducted to
support this label change provides critical information for
physicians and women as they plan for pregnancy and appropriate
disease management. This new label underscores UCB's commitment to
delivering value to underserved patient populations and improving
their overall treatment experience."

Chronic rheumatic diseases such as rheumatoid arthritis (RA),
axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA)
frequently manifest in women of childbearing age,[3] with RA, for
example affecting three times more women than men.[4] The
consequences of active disease in pregnancy can have serious
implications for both mother and infant, including an increased risk
of miscarriage,[5] an increased risk of preterm delivery, the need
for a cesarean, and the infant being small for gestational age.[6]

Adequate disease control is crucial to ensure the best fetal and
maternal health, since high disease activity during pregnancy is
associated with an increased risk of adverse pregnancy
outcomes.[7]-[11] Despite the perception that disease activity
spontaneously improves during pregnancy, approximately 50% of women
with chronic rheumatic disease need effective therapeutic
intervention and are faced with difficult questions regarding the
impact of active disease on their baby and the safety of different
therapies during pregnancy.[12]-[16] As such, there is an evident
need for effective and well tolerated treatment during pregnancy.[8]
Additionally, women who are considering breastfeeding, along with
their treating physicians, often face a conflict between the risks of
maternal medications needed for postpartum disease control and the
optimal nutritional health of the child.

UCB has been leading the way in studying how biologic drugs impact
women of childbearing age. Two key areas of focus are the transfer of
a biologic drug through the placenta to the fetus and via the
mother's breast milk to the infant. Anti-TNF lactation data
historically has been based on case reports without any controlled
studies. However, UCB is changing the way this research is conducted.
The findings from two, first-of-their-kind studies have strong
implications for this patient population as they consider pregnancy.
Based on results from the landmark CRIB study, there is no to minimal
placental transfer evident from mother to child during pregnancy.
Data from CRADLE, the prospective pharmacokinetic trial measuring the
presence of an anti-TNF in breast milk, found minimal transfer of
CIMZIA during lactation.

The approval of the CIMZIA label change in the EU is based on data
from the post marketing CRIB and CRADLE studies as well as our
pregnancy outcomes data. The studies included women with rheumatoid
arthritis, psoriatic arthritis, axial spondyloarthritis, and Crohn's
Disease (CD). In the EU, CIMZIA is not indicated in CD.

About the CRIB Study[1]

CRIB was a pharmacokinetic study assessing the potential level of
placental transfer of certolizumab pegol (CZP) from pregnant women to
their infants. The study followed sixteen women (>= 30 weeks
gestation) who were already receiving CZP for approved indications.

The study found that CZP levels were below the lower limit of
quantification in 13 out of 14 infant blood samples at birth, and in
all samples at weeks four and eight. One infant had a minimal CZP
level of 0.042µg/mL (infant/mother ratio of 0.09%). No anti-CZP
antibodies were detected in mothers, umbilical cords, or infants.
These data indicate no to minimal placental transfer of CZP from
mothers to infants, suggesting lack of in utero fetal exposure during
the third trimester.

In CRIB, adverse events experienced by the infants did not show
any patterns or clusters of events suggesting a specific safety
signal in children. Safety data in the mothers were in line with the
known safety profile of CZP and pregnancy profile of these underlying
diseases.

About the CRADLE Study[2]

The primary objectives of the CRADLE pharmacokinetic study were to
determine the concentration of CZP in human breast milk and the
average daily infant dose, an estimation of the daily dose of
maternal CZP ingested by the infant over the dosing interval.

Among 137 breast milk samples from 17 mothers, all samples had CZP
concentrations that were minimal, less than 3 times the lower limit
of quantification and less than 1% of the expected therapeutic dose.
A post-hoc analysis of the relative infant dose (RID) of CZP in
breast milk was calculated and ranged from 0.04% to 0.30%. The RID is
a useful parameter for assessing drug safety in breastfeeding and
experts consider a RID that is less than 10% to be unlikely of
concern to infant wellbeing.

In CRADLE, adverse events in the infants of mothers exposed to CZP
were consistent with those occurring in unexposed infants of similar
age. Adverse events in mothers exposed to CZP were consistent with
the known safety profile of CZP.

About Pregnancy Outcomes Data

Data from more than 500 prospectively collected pregnancies
exposed to CIMZIA® with known pregnancy outcomes, including more than
400 pregnancies exposed during the first trimester, does not indicate
a malformative effect of CIMZIA. However, the available clinical
experience is too limited to, with a reasonable certainty, conclude
that there is no increased risk associated with CIMZIA administration
during pregnancy. CIMZIA should only be used during pregnancy if
clinically needed.

About CIMZIA® in the EU/EEA

In the EU, CIMZIA® in combination with methotrexate (MTX) is
indicated for the treatment of moderate to severe active RA in adult
patients inadequately responsive to disease-modifying anti-rheumatic
drugs (DMARDs) including MTX.

CIMZIA can be given as monotherapy in case of intolerance to MTX
or when continued treatment with MTX is inappropriate. CIMZIA in
combination with MTX is also indicated for the treatment of severe,
active and progressive RA in adults not previously treated with MTX
or other DMARDs. CIMZIA has been shown to reduce the rate of
progression of joint damage as measured by X-ray and to improve
physical function, when given in combination with MTX.

CIMZIA, in combination with MTX, is also indicated for the
treatment of active psoriatic arthritis in adults when the response
to previous DMARD therapy has been inadequate. CIMZIA can be given as
monotherapy in case of intolerance to MTX or when continued treatment
with MTX is inappropriate.

CIMZIA is also indicated in the EU for the treatment of adult
patients with severe active axial spondyloarthritis (axSpA),
comprising:

- Ankylosing spondylitis (AS) - adults with severe active AS who have
had an inadequate response to, or are intolerant to non-steroidal
anti-inflammatory drugs (NSAIDs).
- Axial spondyloarthritis (axSpA) without radiographic evidence of AS
- adults with severe active axSpA without radiographic evidence of
AS but with objective signs of inflammation by elevated C-reactive
protein (CRP) and/or Magnetic Resonance Imaging (MRI) who have had
an inadequate response to, or are intolerant to NSAIDs.

About CIMZIA® in Fertility, Pregnancy and Lactation in the
EU/EEA

Women of childbearing potential

The use of adequate contraception should be considered for women
of childbearing potential. For women planning pregnancy, continued
contraception may be considered for 5 months after the last CIMZIA®
dose due to its elimination rate, but the need for treatment of the
woman should also be taken into account (see below).

Pregnancy

Data from more than 500 prospectively collected pregnancies
exposed to CIMZIA® with known pregnancy outcomes, including more than
400 pregnancies exposed during the first trimester, does not indicate
a malformative effect of CIMZIA. However, the available clinical
experience is too limited to, with a reasonable certainty, conclude
that there is no increased risk associated with CIMZIA administration
during pregnancy.

Animal studies using a rodent anti-rat TNF? did not reveal
evidence of impaired fertility or harm to the foetus. However, these
are insufficient with respect to human reproductive toxicity. Due to
its inhibition of TNF?, CIMZIA administered during pregnancy could
affect normal immune response in the newborn.

CIMZIA should only be used during pregnancy if clinically needed.
Non-clinical studies suggest low or negligible level of placental
transfer of a homologue Fab-fragment of certolizumab pegol (no Fc
region).

In a clinical study 16 women were treated with certolizumab pegol
(200 mg every 2 weeks or 400 mg every 4 weeks) during pregnancy.
Certolizumab pegol plasma concentrations measured in 14 infants at
birth were Below the Limit of Quantification (BLQ) in 13 samples; one
was 0.042 µg/ml with an infant/mother plasma ratio at birth of 0.09%.
At Week 4 and Week 8, all infant concentrations were BLQ. The
clinical significance of low levels certolizumab pegol for infants is
unknown. It is recommended to wait a minimum of 5 months following
the mother's last CIMZIA administration during pregnancy before
administration of live or live-attenuated vaccines (e.g. BCG
vaccine), unless the benefit of the vaccination clearly outweighs the
theoretical risk of administration of live or live-attenuated
vaccines to the infants.

Breastfeeding

In a clinical study in 17 lactating women treated with CIMZIA®,
minimal transfer of certolizumab pegol from plasma to breast milk was
observed. The percentage of the maternal certolizumab pegol dose that
was reaching an infant during a 24 hour period was estimated to 0.04%
to 0.30%. In addition, since certolizumab pegol is a protein that is
degraded in the gastrointestinal tract after oral administration, the
absolute bioavailability is expected to be very low in a breastfed
infant. Consequently, CIMZIA can be used during breastfeeding.

Important Safety Information about CIMZIA® in the EU/EEA

CIMZIA® was studied in 4,049 patients with rheumatoid arthritis
(RA) in controlled and open label trials for up to 92 months. The
commonly reported adverse reactions (1-10%) in clinical trials with
CIMZIA® and post-marketing were viral infections (includes herpes,
papillomavirus, influenza), bacterial infections (including abscess),
rash, headache (including migraine), asthaenia, leukopaenia
(including lymphopaenia, neutropaenia), eosinophilic disorder, pain
(any sites), pyrexia, sensory abnormalities, hypertension, pruritus
(any sites), hepatitis (including hepatic enzyme increase), injection
site reactions, and nausea. Serious adverse reactions include sepsis,
opportunistic infections, tuberculosis, herpes zoster, lymphoma,
leukaemia, solid organ tumours, angioneurotic oedema,
cardiomyopathies (includes heart failure), ischemic coronary artery
disorders, pancytopaenia, hypercoagulation (including
thrombophlebitis, pulmonary embolism), cerebrovascular accident,
vasculitis, hepatitis/hepatopathy (includes cirrhosis), and renal
impairment/nephropathy (includes nephritis). In RA controlled
clinical trials, 4.4% of patients discontinued taking CIMZIA® due to
adverse events vs. 2.7% for placebo.

CIMZIA® is contraindicated in patients with hypersensitivity to
the active substance or any of the excipients, active tuberculosis or
other severe infections such as sepsis or opportunistic infections or
moderate-to-severe heart failure.

Serious infections including sepsis, tuberculosis and
opportunistic infections have been reported in patients receiving
CIMZIA®. Some of these events have been fatal. Monitor patients
closely for signs and symptoms of infections including tuberculosis
before, during, and after treatment with CIMZIA®. Treatment with
CIMZIA® must not be initiated in patients with a clinically important
active infection. If an infection develops, monitor carefully and
stop CIMZIA® if infection becomes serious. Before initiation of
therapy with CIMZIA®, all patients must be evaluated for both active
and inactive (latent) tuberculosis infection. If active tuberculosis
is diagnosed prior to or during treatment, CIMZIA® therapy must not
be initiated and must be discontinued. If latent tuberculosis is
diagnosed, appropriate anti-tuberculosis therapy must be started
before initiating treatment with CIMZIA®. Patients should be
instructed to seek medical advice if signs/symptoms (e.g. persistent
cough, wasting/weight loss, low grade fever, listlessness) suggestive
of tuberculosis occur during or after therapy with CIMZIA®.

Reactivation of hepatitis B has occurred in patients receiving a
TNF-antagonist including CIMZIA® who are chronic carriers of the
virus (i.e. surface antigen positive). Some cases have had a fatal
outcome. Patients should be tested for HBV infection before
initiating treatment with CIMZIA®. Carriers of HBV who require
treatment with CIMZIA® should be closely monitored and in the case of
HBV reactivation CIMZIA® should be stopped and effective anti-viral
therapy with appropriate supportive treatment should be initiated.

TNF-antagonists including CIMZIA® may increase the risk of new
onset or exacerbation of clinical symptoms and/or radiographic
evidence of demyelinating disease; of formation of autoantibodies and
uncommonly of the development of a lupus-like syndrome; of severe
hypersensitivity reactions. If a patient develops any of these
adverse reactions, CIMZIA® should be discontinued and appropriate
therapy instituted.

With the current knowledge, a possible risk for the development of
lymphomas, leukaemia or other malignancies in patients treated with a
TNF-antagonist cannot be excluded. Rare cases of neurological
disorders, including seizure disorder, neuritis and peripheral
neuropathy, have been reported in patients treated with CIMZIA®.

Adverse reactions of the haematologic system, including medically
significant cytopaenia, have been infrequently reported with CIMZIA®.
Advise all patients to seek immediate medical attention if they
develop signs and symptoms suggestive of blood dyscrasias or
infection (e.g., persistent fever, bruising, bleeding, pallor) while
on CIMZIA®. Consider discontinuation of CIMZIA® therapy in patients
with confirmed significant haematological abnormalities.

The use of CIMZIA® in combination with anakinra or abatacept is
not recommended due to a potential increased risk of serious
infections. As no data are available, CIMZIA® should not be
administered concurrently with live vaccines. The 14-day half-life of
CIMZIA® should be taken into consideration if a surgical procedure is
planned. A patient who requires surgery while on CIMZIA® should be
closely monitored for infections.

CIMZIA® was studied in 325 patients with active axial
spondyloarthritis (axSpA) in a placebo-controlled clinical trial for
up to 30 months and in 409 patients with psoriatic arthritis (PsA) in
a placebo-controlled clinical trial for up to 30 months. The safety
profile for axSpA and PsA patients treated with CIMZIA® was
consistent with the safety profile in RA and previous experience with
CIMZIA®.

Please consult the full prescribing information in relation to
other side effects, full safety and prescribing information. European
SmPC date of revision December 2017. http://www.ema.europa.eu/docs/en
_GB/document_library/EPAR_-_Product_Information/human/001037/WC500069
763.pdf

CIMZIA® is a registered trademark of the UCB Group of Companies.

Corporate Communications Investor Relations Brand
Communications
France Nivelle, Antje Witte, Andrea
Levin Christopher,
Global Communications, UCB Investor Relations, UCB Immunology
Communications, UCB
T +32.2.559.9178, T +32.2.559.94.14, T
+1.404.483.7329
france.nivelle@ucb.com antje.witte@ucb.com
andrea.levin@ucb.com

Laurent Schots,
Media Relations, UCB
T +32.2.559.92.64,
laurent.schots@ucb.com

ots Originaltext: UCB Pharma
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biopharmaceutical company focused on the discovery and development of
innovative medicines and solutions to transform the lives of people
living with severe diseases of the immune system or of the central
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