UCB's Cimzia(R) (certolizumab pegol), Shows Rapid and Sustained Clinical Response in Adult Patients Living with Moderate to Severe Rheumatoid Arthritis

UCB's Cimzia(R) (certolizumab pegol), Shows Rapid and Sustained Clinical
Response in Adult Patients Living with Moderate to Severe Rheumatoid Arthritis
-- In adult patients with moderate to severely active rheumatoid arthritis,
Cimzia(R) provided rapid and sustained improvements in ACR20, physical
function, fatigue and pain as early as the first week, with sustained relief
up to 100 weeks

PHILADELPHIA, Oct. 17 /PRNewswire/ -- UCB today announced data that showed
rapid and sustained improvements in ACR20, physical function, pain and fatigue
of rheumatoid arthritis (RA) as early as the first week, and inhibition of
progression of structural joint damage (seen at week 24) following treatment
with Cimzia® (certolizumab pegol), together with methotrexate (MTX), was
sustained up to 100 weeks. Cimzia® is approved for the treatment of adult
patients with moderately to severely active rheumatoid arthritis. Cimzia® can
be dosed at 400 mg initially and at weeks 2 and 4, followed by 200 mg every
other week; for maintenance dosing, 400 mg every 4 weeks can be considered.

Also presented at the Annual Scientific Meeting of the American College of
Rheumatology (ACR) in Philadelphia data from a post hoc analysis() showed the
speed of developing a clinical response to treatment with 200 mg Cimzia® and
MTX, was important in improving long-term outcomes for patients living with
active RA. The analysis found most patients achieved early control at Week 6.
These patients had significantly better control of symptoms and significantly
better improvements in pain and physical function at one year, compared to
patients who achieved a later response at Week 12.

"These recently published data have shown Cimzia® to work rapidly, and
demonstrate that an early response to treatment is associated with greater
improvements in long-term outcomes," said lead investigator Edward Keystone,
M.D., at The Rebecca MacDonald Center for Arthritis, Mount Sinai Hospital, The
University of Toronto. "The data also confirm the rapid and sustained effect
of Cimzia® in providing effective and clinically meaningful relief of
rheumatoid arthritis, and reducing disease progression," he added. "This
highlights the importance of getting the disease under control quickly in this
debilitating condition which helps improve overall quality of life."

The post hoc analysis() presented at the meeting investigated the relationship
between the kinetics of response and long-term outcomes in patients who
responded to treatment with 200 mg Cimzia® every 2 weeks and MTX, as measured
by ACR20 response or change in DAS28 of greater than or equal to 1.2 from
baseline.

Early Week 6 responders had significantly higher ACR20, ACR50 and ACR70
responses at Week 52, compared to the later Week 12 responders [ACR20 83.1%
versus 66.7%; ACR50 66.7% versus 34.5%; and ACR70 39.0% versus 16.1%,
respectively (p < 0.001)]. Patients with an early ACR20 response at Week 6
also experienced significantly greater improvements in physical function
(HAQ-DI) and pain relief (VAS), compared to later Week 12 responders, and
early Week 6 Disease Activity Score (DAS28) responders reported significantly
greater pain relief (p < 0.001).

Radiographic data presented from the RAPID 1* open-label extension study found
the inhibition of progression of structural joint damage observed from
baseline to Week 24 and Week 52 was maintained out to Week 100 in patients who
completed treatment with Cimzia® and MTX. The mean change from baseline in
modified total Sharp score (mTSS)(b) for the combined Cimzia® dose groups at
Week 100 was 0.59.

In the same study rapid improvements in ACR(a) scores were sustained up to 100
weeks in patients maintained on open-label treatment with 400 mg Cimzia® every
2 weeks and MTX in the RAPID 1. ACR20 response rates at Week 100, in patients
who completed treatment with Cimzia® were 68.2% and 69.5% for patients who
originally received Cimzia® 200 mg or 400 mg every 2 weeks plus MTX,
respectively. ACR50 response rates were 55.2% and 51.5% respectively. Similar
results were also observed for DAS28, and patient reported outcomes such as
physical function and health-related quality of life.

These and other Cimzia® data are available on display during the 2009 Annual
Scientific Meeting of the American College of Rheumatology in Philadelphia,
Oct. 17 - 21.

Serious and sometimes fatal side effects have been reported with Cimzia®,
including tuberculosis (TB), bacterial sepsis, invasive fungal infections
(such as histoplasmosis), and infections due to other opportunistic pathogens.
In pre-marketing controlled trials of all patient populations combined the
most common adverse reactions (greater than or equal to 8%) were upper
respiratory infections (18%), rash (9%) and urinary tract infections (8%).

*About RAPID 1
RAPID 1 is a Phase III double-blind placebo-controlled trial, involving 982
adults, that was designed to establish the efficacy and tolerability of
certolizumab pegol together with MTX, in the treatment of active RA in
patients who did not adequately respond to conventional treatment. Patients
were randomly allocated to receive one of three treatment regimens: 393
patients received certolizumab pegol 400 mg and at Weeks 0, 2 and 4, then 200
mg every two weeks; 390 patients received certolizumab pegol 400 mg every 2
weeks; 199 patients received placebo every 2 weeks. RAPID 1 met co-primary
endpoints: ACR20 response rate at Week 24 and change from baseline in mTSS at
Week 52. Significantly more patients in the certolizumab pegol 200 mg and 400
mg groups achieved an ACR20 response versus placebo (p less than or equal to
0.001); rates at Week 24 were 58.8%, 60.8%, and 13.6%, respectively, and
remained significant at Week 52 (p less than or equal to 0.001). Certolizumab
pegol 200 mg and 400 mg also significantly inhibited radiographic progression;
mean changes from baseline in mTSS at Week 52 were 0.4 and 0.2, respectively,
versus 2.8 for placebo (rank analysis p less than or equal to 0.001).
Certolizumab pegol treated patients reported rapid, significant and clinically
meaningful improvements in physical function versus placebo (p less than or
equal to 0.001).

(+) Post hoc analysis of RAPID 1
The post hoc analysis of the RAPID 1 study aimed to determine if a more rapid
response to certolizumab pegol, together with MTX, was associated with better
long-term improvements in physical function, and relief of pain and fatigue,
in the treatment of active RA in patients who did not respond to conventional
treatment. Patients who responded to treatment with certolizumab pegol 200 mg
every two weeks by Week 12 were divided into two subgroups: The earlier Week 6
responders and later Week 12 responders based on responder definitions: ACR20
response or DAS28 change of greater than or equal to 1.2 from baseline. The
early Week 6 DAS and ACR20 responders had a higher probability of achieving
ACR20/50/70 scores at Week 52 (p < 0.001). By ACR20 definition, 83.1% of the
early Week 6 responders maintained an ACR20 response at Week 52 compared to
66.7% of the later Week 12 responders (p < 0.001).

(++) Open label extension study to RAPID 1(028)
The Phase III, open-label extension (OLE) study to RAPID 1 is investigating
the long-term efficacy and safety of subcutaneous certolizumab pegol (400 mg
every 2 weeks) together with methotrexate in the treatment of signs and
symptoms and in the prevention of joint damage in patients with active RA.
Patients completing RAPID 1 through 52 weeks (completers), or who were ACR20
nonresponders at Week 12 (confirmed at Week 14) and were to be withdrawn from
the study at Week 16 (withdrawers), could continue in the 028 study. The
open-label extension study continued to evaluate the effects of certolizumab
pegol( )over two years. This analysis was performed in completers (n= 508)
with 100 weeks of exposure from RAPID 1 baseline. 95.8% of completers entered
open-label treatment, and of these, 91.1% continued in the study after 100
Weeks. ACR response rates in these patients were sustained throughout the
study. At Week 100, ACR20 response rates were 68.2% and 69.5% in patients who
originally received certolizumab pegol 200 mg or 400 mg plus MTX,
respectively. ACR50 response rates were 55.2% and 51.5 % respectively. At Week
100, 72.4% and 77.3% of certolizumab pegol 200 mg or 400 mg completers
respectively, were mTSS non-progressors, as defined by a change from RAPID 1
baseline in mTSS of less than or equal to 0.05.

(a)ACR (American College of Rheumatology) response scores measure improvement
in the tender and swollen joint count and also include assessment of the
following five parameters: patient's global assessment, physician's global
assessment, patient's assessment of pain, degree of disability, and level of
acute-phase reactant. ACR20 is achieved when there is 20% improvement in the
tender and swollen joint count as well as a 20% improvement in at least three
of the five parameters. ACR50 and ACR70 are an extension of these criteria
corresponding to a 50% and 70% improvement respectively.

(b)The modified total Sharp score (mTSS) is a measurement used to assess
changes in bone erosion and joint-space narrowing measured by X-ray. A smaller
change in mTSS reflects less progression of joint damage.

About CIMZIA®
Cimzia®is the only PEGylated anti-TNF (Tumour Necrosis Factor). Cimzia® has a
high affinity for human TNF-alpha, selectively neutralising the
pathophysiological effects of TNF-alpha. Over the past decade, TNF-alpha has
emerged as a major target of basic research and clinical investigation. This
cytokine plays a key role in mediating pathological inflammation, and excess
TNF-alpha production has been directly implicated in a wide variety of
diseases. The U.S. Food and Drug Administration (FDA) has approved Cimzia® for
reducing signs and symptoms of Crohn's disease and maintaining clinical
response in adult patients with moderate to severe active disease who have had
an inadequate response to conventional therapy and for the treatment of adults
with moderate to severely active rheumatoid arthritis. Cimzia® was approved in
Switzerland for induction of a clinical response and for the maintenance of a
clinical response and remission in patients with active Crohn's disease who
have not responded adequately to conventional treatment in September 2007. UCB
is also developing Cimzia®in other autoimmune disease indications. Cimzia® is
a registered trademark of UCB PHARMA S.A.

IMPORTANT SAFETY INFORMATION

Risk of Serious Infections
Patients treated with Cimzia® are at an 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. Cimzia® should be discontinued if a patient
develops a serious infection or sepsis. Reported infections include:

-- Active tuberculosis, including reactivation of latent tuberculosis.
Patients with tuberculosis have frequently presented with disseminated
or extrapulmonary disease. Patients should be tested for latent
tuberculosis before Cimzia® use and during therapy. Treatment for
latent infection should be initiated prior to Cimzia® use.
-- Invasive fungal infections, including histoplasmosis ,
coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and
pneumocystosis. Patients with histoplasmosis or other invasive fungal
infections may present with disseminated, rather than localized
disease.
Antigen and antibody testing for histoplasmosis may be negative in
some
patients with active infection. Empiric anti-fungal therapy should be
considered in patients at risk for invasive fungal infections who
develop severe systemic illness .

-- Bacterial, viral and other infections due to opportunistic pathogens.

The risks and benefits of treatment with Cimzia® 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 Cimzia®, including
the possible development of tuberculosis in patients who tested negative for
latent tuberculosis infection prior to initiating therapy.

Serious and sometimes fatal infection due to bacterial, mycobacterial,
invasive fungal, viral or other opportunistic pathogens has been reported in
patients receiving TNF-blocking agents. Among opportunistic infections,
tuberculosis, histoplasmosis, aspergillosis, candidiasis, coccidioidomycosis,
listeriosis, and pneumocystosis were the most common. Treatment with Cimzia®
should not be initiated in patients with an active infection, including
clinically important localized infections. Cimzia® should be discontinued if a
patient develops a serious infection or sepsis. Patients who develop a new
infection during treatment with Cimzia® should be closely monitored, undergo a
prompt and complete diagnostic workup appropriate for immunocompromised
patients, and appropriate antimicrobial therapy should be initiated.
Appropriate empiric antifungal therapy should also be considered while a
diagnostic workup is performed for patients who develop a serious systemic
illness and reside or travel in regions where mycoses are endemic.

Malignancies
During controlled and open-labeled portions of Cimzia® studies of Crohn's
disease and other diseases, malignancies (excluding non-melanoma skin cancer)
were observed at a rate of 0.5 per 100 patient-years among 4,650
Cimzia®-treated patients versus a rate of 0.6 per 100 patient-years among
1,319 placebo-treated patients. In studies of Cimzia® for Crohn's disease and
other investigational uses, there was one case of lymphoma among 2,657
Cimzia®-treated patients and one case of Hodgkin lymphoma among 1,319
placebo-treated patients. In Cimzia® RA clinical trials (placebo-controlled
and open label) a total of three cases of lymphoma were observed among 2,367
patients. This is approximately 2-fold higher than expected in the general
population. Patients with RA, particularly those with highly active disease,
are at a higher risk for the development of lymphoma. The potential role of
TNF blocker therapy in the development of malignancies is not known.

Heart Failure
Cases of worsening congestive heart failure (CHF) and new onset CHF have been
reported with TNF blockers. Cimzia® has not been formally studied in patients
with CHF. Exercise caution when using Cimzia® in patients who have heart
failure and monitor them carefully.

Hypersensitivity
Symptoms compatible with hypersensitivity reactions, including angioedema,
dyspnea, hypotension, rash, serum sickness, and urticaria, have been reported
rarely following Cimzia® administration. If such reactions occur, discontinue
further administration of Cimzia® and institute appropriate therapy.

Hepatitis B Reactivation
Use of TNF blockers, including Cimzia®, may increase the risk of reactivation
of hepatitis B virus (HBV) in patients who are chronic carriers of this virus.
Some cases have been fatal. Evaluate patients at risk for HBV infection for
prior evidence of HBV infection before initiating Cimzia® therapy. Exercise
caution in prescribing Cimzia® for patients identified as carriers of HBV,
with careful evaluation and monitoring prior to and during treatment. In
patients who develop HBV reactivation, discontinue Cimzia® and initiate
effective anti-viral therapy with appropriate supportive treatment.

Neurologic Reactions
Use of TNF blockers, including Cimzia®, has been associated with rare cases of
new onset or exacerbation of clinical symptoms and/or radiographic evidence of
demyelinating disease. Rare cases of neurological disorders, including seizure
disorder, optic neuritis, and peripheral neuropathy have been reported in
patients treated with Cimzia®. Exercise caution in considering the use of
Cimzia® in patients with these disorders.

Hematologic Reactions
Rare reports of pancytopenia, including aplastic anemia, have been reported
with TNF blockers. Medically significant cytopenia (e.g., leukopenia,
pancytopenia, thrombocytopenia) has 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 hematologic
abnormalities.

Drug Interactions
An increased risk of serious infections has been seen in clinical trials of
other TNF blocking agents used in combination with anakinra or abatacept.
Formal drug interaction studies have not been performed with rituximab or
natalizumab; however because of the nature of the adverse events seen with
these combinations with TNF blocker therapy, similar toxicities may also
result from the use of Cimzia® in these combinations. Therefore, the
combination of Cimzia® with anakinra, abatcept, rituximab, or natalizumab is
not recommended. Interference with certain coagulation assays has been
detected in patients treated with Cimzia® . There is no evidence that Cimzia®
therapy has an effect on in vivo coagulation. Cimzia® may cause erroneously
elevated aPTT assay results in patients without coagulation abnormalities.

Autoimmunity
Treatment with Cimzia® may result in the formation of autoantibodies and,
rarely, in the development of a lupus-like syndrome. Discontinue treatment if
symptoms of lupus-like syndrome develop.

Immunizations
Do not administer live vaccines or attenuated vaccines concurrently with
Cimzia®.

Adverse Reactions
In controlled Crohn's clinical trials, the most common adverse events that
occurred in greater than or equal to 5% of Cimzia® patients (n=620) and more
frequently than with placebo (n=614) were upper respiratory infection (20%
Cimzia®, 13% placebo), urinary tract infection (7% Cimzia®, 6% placebo), and
arthralgia (6% Cimzia®, 4% placebo). The proportion of patients who
discontinued treatment due to adverse reactions in the controlled clinical
studies was 8% for Cimzia® and 7% for placebo.

In controlled RA clinical trials, the most common adverse events that occurred
in greater than or equal to 3% of patients taking Cimzia® 200 mg every other
week with concomitant methotrexate (n=640) and more frequently than with
placebo with concomitant methotrexate (n=324) were upper respiratory tract
infection (6% Cimzia®, 2% placebo), headache (5% Cimzia®, 4% placebo),
hypertension (5% Cimzia®, 2% placebo), nasopharyngitis (5% Cimzia®, 1%
placebo), back pain (4% Cimzia®, 1% placebo), pyrexia (3% Cimzia®, 2%
placebo), pharyngitis (3% Cimzia®, 1% placebo), rash (3% Cimzia®, 1% placebo),
acute bronchitis (3% Cimzia®, 1% placebo), fatigue (3% Cimzia®, 1% placebo).
Hypertensive adverse reactions were observed more frequently in patients
receiving Cimzia® than in controls. These adverse reactions occurred more
frequently among patients with a baseline history of hypertension and among
patients receiving concomitant corticosteroids and non-steroidal
anti-inflammatory drugs. Patients receiving Cimzia® 400mg as monotherapy
every 4 weeks in RA controlled clinical trials had similar adverse reactions
to those patients receiving Cimzia® 200mg every other week. The proportion of
patients who discontinued treatment due to adverse reactions in the controlled
clinical studies was 5% for Cimzia® and 2.5% for placebo.
Please see full prescribing information at
www.cimzia.com/rheumatoidarthritis/pdf/Prescribing_Information.pdf

About UCBUCB, Brussels, Belgium (www.ucb.com) is a biopharmaceutical company
dedicated to the research, development and commercialization of innovative
medicines with a focus on the fields of central nervous system and immunology
disorders. Employing approximately 10,000 people in over 40 countries, UCB
generated revenue of EUR 3.6 billion in 2008. UCB is listed on Euronext
Brussels (symbol: UCB).

Forward-looking statementsThis press release contains forward-looking
statements based on current plans, estimates and beliefs of management. Such
statements are subject to risks and uncertainties that may cause actual
results to be materially different from those that may be implied by such
forward-looking statements contained in this press release. Important factors
that could result in such differences include: changes in general economic,
business and competitive conditions, effects of future judicial decisions,
changes in regulation, exchange rate fluctuations and hiring and retention of
its employees.

SOURCE UCB

Bert Kelly of UCB Immunology Public Relations, +1-770-970-8491,
Bert.kelly@ucb.com; or Scott Fleming of Global Immunology Public Relations,
+44-770-277-7378, Scott.fleming@ucb.com