Phase 3 Data Show Intravenous Golimumab Inhibited Radiographic
Progression in Patients with Active Rheumatoid Arthritis
WASHINGTON, Nov. 12, 2012 /PRNewswire/ -- New Phase 3
findings from a Janssen Research & Development, LLC
(Janssen)-sponsored study showed treatment with the investigational
intravenous (I.V.) therapy golimumab, a tumor necrosis factor (TNF)
inhibitor, significantly inhibited radiographic progression in
patients with active moderate to severe rheumatoid arthritis (RA)
despite treatment with methotrexate. Analysis of study
patients' X-rays showed significant inhibition of the progression
of structural damage at week 24 in greater proportions of patients
receiving I.V. golimumab plus methotrexate compared with patients
receiving placebo plus methotrexate. The inhibition of
structural damage progression was maintained in patients randomized
to I.V. golimumab through week 52, and inhibition of structural
damage progression was observed at week 52 in patients receiving
placebo who crossed over to I.V. golimumab at week 24.
Treatment with I.V. golimumab plus methotrexate also led to
improvements in signs and symptoms and disease activity with nearly
60 percent of patients achieving at least a 20 percent improvement
in the American College of Rheumatology (ACR 20) score at week 14,
the study's primary endpoint, and nearly two-thirds of patients
achieving that response at week 52. These data are being
presented at the 2012 Annual Meeting of the American College of
Rheumatology.
In September, Janssen announced the submission of a Biologics
License Application (BLA) to the U.S. Food and Drug Administration
(FDA) requesting approval of I.V. golimumab in combination with
methotrexate for the treatment of adults with moderately to
severely active RA. Golimumab is currently marketed as
SIMPONI® (golimumab), a subcutaneous injection approved
by the United States Food and Drug Administration (FDA) for the
treatment of moderately to severely active RA with the medicine
methotrexate, active psoriatic arthritis alone or with the medicine
methotrexate and active ankylosing spondylitis.
"These Phase 3 data show treatment with intravenous golimumab
plus methotrexate induced and maintained improvements in the signs
and symptoms of rheumatoid arthritis, and inhibited the progression
of structural damage. Such findings are encouraging for
rheumatologists and patients," said Rene Westhovens, M.D., Ph.D.,
Professor at the Department of Rheumatology, KU Leuven,
Belgium, and study
investigator. "Through week 52, intravenously administered
golimumab showed a consistent benefit-to-risk profile compared with
previously reported week 24 data."
In the Phase 3 Multicenter, Randomized, Double-blind,
Placebo-controlled Trial of Golimumab, an Anti-TNF-alpha Monoclonal
Antibody, Administered Intravenously, in Subjects with Active
Rheumatoid Arthritis Despite Methotrexate Therapy (GO-FURTHER),
patients were randomized to receive I.V. golimumab 2 mg/kg or
placebo, via a 30-minute infusion, plus methotrexate at weeks 0, 4
and then every 8 weeks. Non-responders to placebo at week 16
were crossed over to receive I.V. golimumab, and all remaining
patients receiving placebo crossed over at week 24.
Radiographic progression was assessed by the change from baseline
in van der Heijde-Sharp (vdH-S)
scores, an X-ray measure of joint destruction, including joint
erosion and joint space narrowing in which higher scores indicate
greater structural damage. At week 24, patients receiving
I.V. golimumab had a mean change (+/- standard deviation) in total
vdH-S score of 0.03 (+/-1.90) from baseline, compared with a mean
change of 1.09 (+/- 3.19) in the placebo group (P <
0.001). At week 52, patients who received the 52-week regimen
of I.V. golimumab had a mean change of 0.13 (+/- 3.11) from
baseline, compared with a mean change of 1.22 (+/- 3.98) in
patients who crossed over from placebo to I.V. golimumab during the
trial (P < 0.001). Patients randomized to I.V.
golimumab and those in the crossover group had a mean change in
total vdH-S score of 0.15 (+/- 1.83) and 0.12 (+/- 2.44),
respectively, from week 24 to 52, supporting inhibition of
structural damage progression in all patients receiving I.V.
golimumab.
Significant proportions of patients receiving I.V. golimumab
also demonstrated improvements in signs and symptoms compared with
patients receiving placebo according to ACR scores, European League
Against Rheumatism (EULAR)/Disease Activity Score (DAS) 28
C-reactive protein (CRP) response criteria and Health Assessment
Questionnaire (HAQ) disability scores at weeks 14 and 24. A
majority of those patients who achieved ACR 20, ACR 50, ACR 70 and
EULAR/DAS 28 CRP good/moderate response by week 24 maintained
response through week 52 (82 percent of ACR20 responders; 71.7
percent of ACR 50 responders; 60.9 percent of ACR 70 responders; 80
percent demonstrating DAS28-CRP good/moderate response). The
EULAR/DAS 28 CRP is a measure of disease activity in patients with
RA that is calculated by assessing the number of tender and swollen
joints (among a total of 28), serum CRP level (indicator of
inflammation), and the patient's assessment of global
health.
Through week 52 of the GO-FURTHER trial, the safety profile of
I.V. golimumab remained consistent with previously reported week 24
data. Through week 24, adverse events (AEs) occurred in 53
percent of patients receiving I.V. golimumab and 49 percent of
patients receiving placebo, and serious AEs were reported in more
I.V. golimumab-treated patients (4 percent) than placebo-treated
patients (2 percent). Rates of AEs and serious AEs at week 52
among patients receiving I.V. golimumab were 65 percent and 9
percent, respectively. There were no serious opportunistic
infections through week 52 of the study. One case of
tuberculosis and one death, a myocardial infarction secondary to
community-acquired pneumonia, were reported in the I.V. golimumab
group. Through week 52, the proportions of infusions and
patients with infusion reactions were 0.7 percent and 3.6 percent,
respectively, (versus 1.1 percent and 3.5 percent at week 24,
respectively).
About GO-FURTHER
The GO-FURTHER trial is a Phase 3,
international multicenter, double-blind, placebo-controlled study
including 592 adults with RA designed to compare ACR 20 response at
week 14 in patients receiving an I.V. golimumab infusion plus
methotrexate compared with patients receiving placebo infusions
plus methotrexate. The trial included patients diagnosed with
active RA who had at least six tender and six swollen joints and
who had been receiving background methotrexate for at least three
months. Patients were randomized 2:1 to receive a 30 (+/- 10)
minute I.V. infusion of golimumab 2 mg/kg or placebo plus
methotrexate at weeks 0, 4, and then every eight weeks. The
primary endpoint of the study was ACR 20 at week 14. At week
16, patients receiving placebo with less than 10 percent
improvement in combined swollen and tender joint counts were
entered into early escape to receive I.V. golimumab 2 mg/kg at week
16 and week 20. All patients receiving placebo crossed over
to I.V. golimumab at week 24. Radiographs of the hands and feet
were taken at baseline, week 24 (week 16 for early escape
participants) and week 52 and were scored using the modified vdHS
score. Week 24 results from the Janssen-sponsored study were
presented earlier this year at the 2012 EULAR Annual Congress and
also appeared in the Annals of the Rheumatic
Diseases.
About Rheumatoid Arthritis
Rheumatoid
Arthritis is a chronic, systemic inflammatory condition that is
often characterized by symptoms that include pain, stiffness and
inflammation, and in some cases, joint destruction and
disability. It is estimated that 1.5 million
Americans[1] and more than 23.5 million
people worldwide[2] are affected by the
condition, for which there is no cure.
About SIMPONI
SIMPONI is a human monoclonal
antibody that targets and neutralizes excess TNF-alpha, a
protein that when overproduced in the body due to chronic
inflammatory diseases can cause inflammation and damage to bones,
cartilage and tissue. SIMPONI is approved in 57 countries for
adult rheumatologic indications, including the United States where SIMPONI received FDA
approval in April 2009 for the
treatment of moderately to severely active rheumatoid arthritis
(RA) with the medicine methotrexate, active psoriatic arthritis
alone or with the medicine methotrexate and active ankylosing
spondylitis. SIMPONI is available either through the
SmartJect® autoinjector or a prefilled syringe as a
subcutaneously administered injection. For more information
about SIMPONI, visit www.SIMPONI.com.
Applications requesting approval of SIMPONI as a subcutaneously
administered anti-TNF-alpha therapy for the treatment of adult
patients with moderately to severely active ulcerative colitis have
been submitted in Europe and the
U.S.
In addition, applications requesting approval of I.V. golimumab
for the treatment of adults with moderately to severely active RA
have been submitted in the U.S. and Europe.
Janssen Biotech, Inc. discovered and developed SIMPONI and
markets the product in the United States. Janssen
pharmaceutical companies market SIMPONI in Canada, Central and South America, the Middle East, Africa and Asia Pacific.
In Japan, Indonesia and Taiwan, Janssen Biotech, Inc. licenses
distribution rights to SIMPONI to Mitsubishi Tanabe Pharma
Corporation and has retained co-marketing rights in those
countries. In Europe, Russia
and Turkey, Janssen Biotech, Inc.
licenses distribution rights to SIMPONI to Schering-Plough
(Ireland) Company, a subsidiary of
Merck & Co., Inc.
The U.S. full prescribing information for SIMPONI can be
accessed at the following link:
http://www.simponi.com/sites/default/files/pdf/prescribing-information.pdf.
For further information about SIMPONI outside of the United States, please consult the relevant
official product information applicable to that country
location
Important Safety Information About SIMPONI Subcutaneous
Formulation
SIMPONI® (golimumab) is a
prescription medicine. SIMPONI® can lower your ability
to fight infections. There are reports of serious infections caused
by bacteria, fungi, or viruses that have spread throughout the
body, including tuberculosis (TB) and histoplasmosis. Some of these
infections have been fatal. Your doctor will test you for TB before
starting SIMPONI® and will monitor you for signs
of TB during treatment. Tell your doctor if you have been in
close contact with people with TB. Tell your doctor if you have
been in a region (such as the Ohio
and Mississippi River Valleys and the Southwest) where certain
fungal infections like histoplasmosis or coccidioidomycosis are
common.
You should not start SIMPONI® if you have any kind of
infection. Tell your doctor if you are prone to or have a history
of infections or have diabetes, HIV or a weak immune system. You
should also tell your doctor if you are currently being treated for
an infection or if you have or develop any signs of an infection
such as:
- fever, sweat, or chills
- muscle aches
- cough
- shortness of breath
- blood in phlegm
- weight loss
- warm, red, or painful skin or sores on your body
- diarrhea or stomach pain
- burning when you urinate or urinate more than normal
- feel very tired
Unusual cancers have been reported in children and teenage
patients taking TNF-blocker medicines. For children and adults
taking TNF blockers, including SIMPONI®, the chances for
getting lymphoma or other cancers may increase. You should tell
your doctor if you have had or develop lymphoma or other
cancers.
Tell your doctor about all the medications you take including
ORENCIA (abatacept), KINERET (anakinra), ACTEMRA (tocilizumab),
RITUXAN (rituximab), or another TNF blocker, or if you are
scheduled to or recently received a vaccine. People taking
SIMPONI® should not receive live vaccines.
Reactivation of hepatitis B virus has been reported in patients
who are carriers of this virus and are taking TNF-blocker
medicines, such as SIMPONI®. Some of these cases have
been fatal. Your doctor should do blood tests before and after you
start treatment with SIMPONI®. Tell your doctor if you
know or think you may be a carrier of hepatitis B virus or if you
experience signs of hepatitis B infection, such as:
- feel very tired
- dark urine
- skin or eyes look yellow
- little or no appetite
- vomiting
- muscle aches
- clay-colored bowel movements
- fevers
- chills
- stomach discomfort
- skin rash
Heart failure can occur or get worse in people who use TNF
blockers, including SIMPONI®. Your doctor will closely
monitor you if you have heart failure. Tell your doctor right away
if you get new or worsening symptoms of heart failure like
shortness of breath or swelling of your lower legs or
feet.
Rarely, people using TNF blockers, including
SIMPONI®, can have nervous system problems such as
multiple sclerosis or Guillain-Barre syndrome. Tell your doctor
right away if you have symptoms like vision changes, weakness in
your arms or legs, or numbness or tingling in any part of your
body.
Serious liver problems can happen in people using TNF blockers,
including SIMPONI®. Contact your doctor immediately if
you develop symptoms such as feeling very tired, skin or eyes look
yellow, poor appetite or vomiting, or pain on the right side of
your stomach.
Low blood counts have been seen with people using TNF blockers,
including SIMPONI®. If this occurs, your body may not
make enough blood cells to help fight infections or help stop
bleeding. Your doctor will check your blood counts before and
during treatment. Tell your doctor if you have signs such as fever,
bruising, bleeding easily, or paleness.
Rarely, people using TNF blockers have developed lupus-like
symptoms. Tell your doctor if you have any symptoms such as a rash
on your cheeks or other parts of the body, sensitivity to the sun,
new joint or muscle pain, becoming very tired, chest pain or
shortness of breath, swelling of the feet, ankles, and/or legs.
New or worse psoriasis symptoms may occur. Tell your doctor if
you develop red scaly patches or raised bumps that are filled with
pus.
Tell your doctor if you are pregnant, planning to become
pregnant or are breastfeeding or have a baby and were using
SIMPONI® during pregnancy. Tell your baby's doctor
before your baby receives any vaccine because of an increased risk
of infection for up to 6 months after birth.
Tell your doctor if you are allergic to rubber or latex. The
needle cover contains dry natural rubber.
Tell your doctor if you have any symptoms of an allergic
reaction while taking SIMPONI® such as hives, swollen
face, breathing trouble, chest pain. Some reactions can be serious
and life-threatening.
Common side effects of SIMPONI® include: upper
respiratory tract infection, reaction at site of injection, and
viral infections.
Please read the Medication Guide for SIMPONI® and
discuss any questions you have with your doctor.
You are encouraged to report negative side effects of
prescription drugs to the FDA. Visit
http://www.fda.gov/Safety/MedWatch/, or call
1-800-FDA-1088.
The U.S. full prescribing information for SIMPONI®
can be accessed at the following link:
http://www.simponi.com/sites/default/files/pdf/prescribing-information.pdf.
About Janssen Research & Development, LLC
At
Janssen Research & Development, LLC, we are united and
energized by one mission—to discover and develop innovative
medicines that ease patients' suffering, and solve the most
important unmet medical needs of our time. As one of the
Janssen Pharmaceutical Companies of Johnson & Johnson, our
strategy is to identify the biggest unmet medical needs and match
them with the best science, internal or external, to find solutions
for patients worldwide. We leverage our world-class discovery and
development expertise, and operational excellence, to bring
innovative, effective treatments in oncology, immunology,
neuroscience, infectious diseases and vaccines, and cardiovascular
and metabolic diseases. For more information on Janssen
R&D, visit http://www.janssenrnd.com/.
[1] Centers for Disease Control and Prevention.
Arthritis-Related Statistics.
http://www.cdc.gov/arthritis/data_statistics/arthritis_related_stats.htm.
Accessed November 10, 2012.
[2] World Health Organization. The global burden of disease:
2004 update. Geneva: WHO Press,
2008.
http://www.who.int/healthinfo/global_burden_disease/GBD_report_2004update_full.pdf.
Accessed November 10, 2012.
SOURCE Janssen Research & Development, LLC