Long-Term Data in Patients Receiving Every-Four-Week Subcutaneous SIMPONI Presented at 2009 EULAR Annual Congress
COPENHAGEN, DENMARK | June 9, 2009 | Findings from open-labeled, uncontrolled extensions of two randomized, placebo-controlled Phase 3 studies showed that subcutaneous (SC) injections of SIMPONI(TM) (golimumab) 50 mg or 100 mg every four weeks provided persistent improvements in the signs and symptoms in patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS). Investigators reported these new data from the long term treatment extensions of the GO-REVEAL and GO-RAISE trials at the 2009 European League Against Rheumatism (EULAR) Annual Congress.
In the Golimumab – A Randomized EValuation of Safety and Efficacy in Subjects with Psoriatic Arthritis Using a Human Anti-TNF MonocLonal Antibody (GO-REVEAL) study, patients with active PsA were randomized to placebo (n=113), SIMPONI 50 mg (n=146) or SIMPONI 100 mg (n=146). Of the 405 patients originally randomized in the Phase 3 study, a two-year observational analysis of 276 patients remaining in the study and evaluated at two years was performed. Sixty-four of 70 patients who received SIMPONI 50 mg and 95 of 130 patients who received SIMPONI 100 mg achieved ACR 20, respectively. Forty-three of 76 patients receiving SIMPONI 50 mg who switched to SIMPONI 100 mg in early escape also achieved ACR 20. At least 50 percent improvement in arthritis signs and symptoms (ACR 50) was seen in 47 of 70 patients receiving SIMPONI 50 mg and 70 of 130 patients receiving SIMPONI 100 mg, respectively, while 70 percent improvement (ACR 70) was seen in 31 of 70 patients and 48 of 130 patients in the SIMPONI 50 mg and 100 mg dose groups, respectively.
In a similar analysis, SIMPONI-treated patients also experienced sustained improvements in skin manifestations of PsA through two years. Patients with greater than three percent Body Surface Area (BSA) psoriasis skin involvement at baseline (n=296) were evaluated for Psoriatic Area and Severity Index (PASI) responses. Of the 296 patients who had at least three percent BSA involved with skin symptoms of PsA, 200 were evaluated at two years. PASI 75 was also observed in 33 of 48 patients receiving SIMPONI 50 mg who did not change dose and 73 of 96 patients receiving SIMPONI 100 mg. Thirty-five of 56 patients receiving SIMPONI 50 mg who switched to SIMPONI 100 mg in early escape also achieved PASI 75.
"According to our findings, patients receiving golimumab 50 mg or 100 mg experienced sustained improvements in the signs and symptoms of psoriatic arthritis through two years of treatment," said Iain B. McInnes, MD, PhD, FRCP, Professor of Experimental Medicine, University of Glasgow, study investigator. "These findings demonstrate the promise and utility of golimumab in treating both the joint and skin manifestations of this disease."
In the open-label, uncontrolled extension of the Golimumab – A Randomized Study in Ankylosing Spondylitis Subjects of a Novel Anti-TNF mAB Injection (SC) Given Every Four Weeks (GO-RAISE) study, patients receiving every-four-week subcutaneous treatment with SIMPONI experienced sustained improvements in the signs and symptoms of AS. As in the GO-REVEAL study, the GO-RAISE findings were based on observed data only, in patients who were followed through two years. Of the 356 patients originally randomized, 286 were evaluated at two years. Improvements in the Assessment in Ankylosing Spondylitis criteria (ASAS 20) were maintained through two years in each of the study arms:
— SIMPONI 50 mg after switch from placebo at week 16 (24 of 31 patients)
— SIMPONI 50 mg after switch from placebo at week 24 (28 of 31 patients)
— SIMPONI 50 mg only (77 of 90 patients)
— SIMPONI 50 mg to 100 mg (7 of 16 patients)
— SIMPONI 100 mg combined (91 of 118 patients)
"In the GO-RAISE trial, treatment with golimumab provided sustained symptom relief to patients living with the chronic inflammatory disease, ankylosing spondylitis," said Jurgen Braun, MD, lead physician at the Rheumazentrum Ruhrgebiet, Professor of Rheumatology at the Free University of Berlin, lead study investigator. "As seen in this study, the possibilities of this new anti-TNF-alpha therapy are encouraging for both the physician and rheumatology patient communities."
In similar analyses from GO-RAISE, investigators also reported that study patients receiving SIMPONI showed sustained improvements in spinal and hip mobility through two years as measured by the Bath Ankylosing Spondylitis Metrology Index (BASMI). Improvements in Mental Component Summary (MCS) and Physical Component Summary (PCS) Short Form (SF)-36 questionnaire scores were also maintained through two years.
"The sustained symptom relief demonstrated in these Phase 3 studies is encouraging," said Robert J. Spiegel, MD, chief medical officer, Schering-Plough Research Institute. "The sustained efficacy and safety SIMPONI demonstrated through two years of observation further support the positive benefit of SIMPONI in patients with psoriatic arthritis and ankylosing spondylitis."
About the GO-REVEAL Trial
The GO-REVEAL trial involved 405 adults with psoriatic arthritis. Patients with at least 3 swollen and tender joints and active psoriatic skin lesions of at least two cm in diameter were randomly assigned to receive SC injections of placebo or SIMPONI (50 or 100 mg) every four weeks for two years. The primary endpoint was ACR 20 response at week 14 for combined SIMPONI groups and individual SIMPONI dose groups vs. placebo. At week 16, patients with inadequate arthritis response were switched to SIMPONI 50 mg (patients originally receiving placebo) or SIMPONI 100 mg (patients originally receiving SIMPONI 50 mg). All patients received SIMPONI from week 24. The trial was unblinded to investigators and patients after all patients reached week 52 and the week 52 database was locked. Investigators could choose to dose escalate patients receiving SIMPONI 50 mg to 100 mg based on clinical judgment. The primary endpoint was ACR 20 response at week 14 for combined SIMPONI groups and individual SIMPONI dose groups vs. placebo.
Through two years, SIMPONI was generally well-tolerated, with nine percent of SIMPONI-treated patients experiencing serious adverse events. Injection site reactions occurred in eight percent of patients receiving SIMPONI. There were no reports of tuberculosis, and one case of histoplasmosis in a patient (SIMPONI 100 mg) living in an endemic area was successfully treated. Malignancies reported through week 104 included basal cell skin cancer (one patient), colon cancer (one patient) and small cell lung cancer (one patient) in patients receiving SIMPONI 50 mg, and basal cell skin cancer (three patients), prostate cancer (one patient), and small cell lung cancer (one patient) in patients receiving SIMPONI 100 mg. Two patients died through two years, one due to a climbing accident (SIMPONI 50 mg) and one due to small cell lung cancer (SIMPONI 100 mg).
About the GO-RAISE Trial
The GO-RAISE trial included 356 patients with active ankylosing spondylitis. Patients were randomized to receive subcutaneous injections of SIMPONI 50 mg or 100 mg or placebo every four weeks. The primary endpoint was the proportion of patients achieving ASAS 20 at week 14. At week 16, patients in the placebo or 50 mg group demonstrating less than 20 percent improvement from baseline in both total back pain and morning stiffness measures were switched to either SIMPONI 50 mg (previously receiving placebo) or SIMPONI 100 mg (previously receiving SIMPONI 50 mg). At week 24, patients still receiving placebo were switched to SIMPONI 50 mg.
Through two years, SIMPONI was generally well tolerated, with 11 percent of SIMPONI-treated patients experiencing serious adverse events. Injection site reactions occurred in 11 percent of patients receiving SIMPONI. There was one case of pulmonary tuberculosis in a patient (SIMPONI 100 mg). Malignancies reported through week 104 consisted of two basal cell skin cancers (one patient on SIMPONI 100 mg, one placebo patient). No deaths occurred.
The GO-REVEAL and GO-RAISE studies were supported by Centocor Ortho Biotech Inc. and Schering-Plough Corporation.
About Psoriatic Arthritis
Psoriatic arthritis is a chronic inflammatory arthropathy manifesting with joint pain and swelling that can lead to joint destruction and debilitation. It is frequently associated with inflamed, scaly, red patches of skin psoriasis and psoriasis nail involvement. Symptoms may include stiffness and tenderness of the joints and surrounding tissue and reduced range of motion. Joints of the hands, wrists, knees, ankles, feet, lower back and neck are commonly affected. Psoriasis affects an estimated two to three percent of the world’s population, and approximately one out of three patients affected by psoriasis may develop psoriatic arthritis. Both men and women are equally affected by psoriatic arthritis, most commonly between the ages 30 and 50, in the peak of their productive years.
About Ankylosing Spondylitis
AS is a painful and progressive form of spinal arthritis, and symptoms of inflammatory back pain often first present in people under the age of 35 years. It typically begins in the late teens and early twenties and in severe cases can result in fusing of the spinal vertebrae and cause structural damage to hips and other joints. Often misdiagnosed as "just back pain" or undifferentiated arthritis, AS is a systemic inflammatory disease that, in addition to its effect on the spine, can affect internal organs, peripheral joints and vision. The Spondylitis Association of America estimates that between 350,000 and one million people in the US suffer from AS.
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. The first once-monthly subcutaneous anti-TNF-alpha therapy, SIMPONI is approved in Canada and the United States and is available either through the SIMPONI SmartJect(TM) autoinjector or a prefilled syringe. The approved dose for SIMPONI in the US and Canada is a 50 mg subcutaneous injection given once a month.
Indications in the US:
In the United States, SIMPONI is indicated for the treatment of moderately to severely active rheumatoid arthritis in adults, in combination with methotrexate; active psoriatic arthritis in adults, alone or in combination with methotrexate; and active ankylosing spondylitis in adults.
Indications in Canada:
In Canada, SIMPONI, in combination with methotrexate (MTX), is indicated for reducing the signs and symptoms in adult patients with moderately to severely active RA; reducing signs and symptoms in adult patients with moderately to severely active PsA, alone or in combination with MTX; and reducing signs and symptoms in adult patients with active AS who have had an inadequate response to conventional therapies.
SIMPONI is also being studied as an intravenous infusion therapy for the treatment of moderately to severely active rheumatoid arthritis.
In March 2008, Centocor Ortho Biotech Inc. and Schering-Plough Corporation announced that a Marketing Authorization Application (MAA) had been submitted to the European Medicines Agency (EMEA) requesting the approval of SIMPONI as a once-monthly subcutaneous treatment for adults with RA, PsA and AS.
Centocor Ortho Biotech Inc. developed and discovered SIMPONI and has exclusive marketing rights to the product in the United States. Following regulatory approvals, Schering-Plough will assume exclusive marketing rights outside the United States except in Japan, Indonesia and Taiwan, where SIMPONI will be co-marketed by Mitsubishi Tanabe Pharma Corporation and Janssen Pharmaceutical Kabushiki Kaisha; Hong Kong, where SIMPONI will be exclusively marketed by Janssen-Cilag; and China, where SIMPONI will be exclusively marketed by Xian-Janssen.
Important Safety Information
SIMPONI(TM) is a prescription medicine. SIMPONI(TM) 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(TM) 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(TM) if you have any kind of infection. Tell your doctor if you are prone to or have a history of infections or have diabetes. 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
Tell your doctor about all the medications you take or if you are scheduled to or recently received a vaccine.
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(TM). Some of these cases have been fatal. Your doctor may do blood tests before and after you start treatment with SIMPONI(TM). 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
— skin or eyes look yellow
— little or no appetite
— vomiting
— muscle aches
— dark urine
— clay-colored bowel movements
— fevers
— chills
— stomach discomfort
— skin rash
If you take SIMPONI(TM) or other TNF blockers, your risk for developing lymphoma or other cancers may increase. You should tell your doctor if you have had or develop lymphoma or other cancers.
Heart failure can occur or get worse in people who use TNF blockers like SIMPONI(TM). Your doctor will monitor you closely 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 can have nervous system problems such as multiple sclerosis. 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.
Liver problems can happen in people using TNF blockers. 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. 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.
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(TM) such as hives, swollen face, breathing trouble, or chest pain. Common side effects of SIMPONI(TM) include: upper respiratory tract infection, nausea, abnormal liver tests, redness at site of injection, high blood pressure, bronchitis, dizziness, sinus infection, flu, runny nose, fever, cold sores, numbness or tingling.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.
The Full Prescribing Information and Medication Guide for SIMPONI will be available at www.SIMPONI.com.
About Centocor Ortho Biotech Inc.
Centocor Ortho Biotech Inc. redefines the standard of care in immunology, nephrology, and oncology. The company was created when Ortho Biotech Inc. merged into Centocor, Inc., and Centocor, Inc. was renamed Centocor Ortho Biotech Inc. Built upon a pioneering history, Centocor Ortho Biotech Inc. harnesses innovations in large-molecule and small-molecule research to create important new therapeutic options. Beyond its innovative medicines, Centocor Ortho Biotech is at the forefront of developing education and public policy initiatives to ensure patients and their families, caregivers, advocates, and healthcare professionals have access to the latest treatment information, support services, and quality care. For more information about Centocor Ortho Biotech, visit www.CentocorOrthoBiotech.com. Centocor Ortho Biotech is a wholly-owned subsidiary of Johnson & Johnson.
About Schering-Plough
Schering-Plough (headquartered in the US) is an innovation-driven, science-centered global health care company. Through its own biopharmaceutical research and collaborations with partners, Schering-Plough creates therapies that help save and improve lives around the world. The company applies its research-and-development platform to human prescription and consumer products as well as to animal health products. Schering-Plough’s vision is to "Earn Trust, Every Day" with the doctors, patients, customers and other stakeholders served by its colleagues around the world. The company is based in Kenilworth, N.J., and its Web site is www.schering-plough.com.
SOURCE Centocor Ortho Biotech Inc.
