Washington, DC, November 12, 2012 – 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-Barré 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/.
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[1] Centers for Disease Control and Prevention. Arthritis-Related Statistics. http://www.cdc.gov/arthritis/data_statistics/arthritis_related_stats.htm. Accessed October 16, 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 October 16, 2012.
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