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New Analysis Shows Efficacy of SIMPONI(TM) (golimumab) in Anti-TNF Experienced Rheumatoid Arthritis Patients

Posted on: Tuesday, 9 June 2009, 17:04 CDT

Anti-TNF Experienced Patients Demonstrated Improvement With Every-Four-Week Subcutaneous SIMPONI Despite Previous Medication or Reason for Discontinuation

COPENHAGEN, June 9 /PRNewswire/ -- A new analysis demonstrated that a greater proportion of patients with moderately to severely active rheumatoid arthritis (RA) who had prior treatment with anti-tumor necrosis factor (TNF)-alpha agents and received subcutaneous injections of SIMPONI(TM) (golimumab) once every four weeks experienced significant improvements in signs and symptoms through week 24, compared with patients receiving placebo. Patients continued to receive stable doses of methotrexate, sulfasalazine and/or hydroxychloroquine if receiving them at baseline. These data were presented at the 2009 European League Against Rheumatism (EULAR) Annual Congress.

Findings from the GOlimumab After Former anti-TNF Therapy Evaluated in RA (GO-AFTER) study, demonstrated that patients previously treated with adalimumab, etanercept or infliximab responded to and tolerated SIMPONI regardless of the type of prior anti-TNF therapy, as well as the number of prior therapies or reason for discontinuation. According to the study, 39 percent of patients receiving SIMPONI whose prior anti-TNF-alpha therapy had been discontinued due to a lack of efficacy achieved at least a 20 percent improvement in arthritis symptoms (ACR 20) at week 14, compared with 18 percent of patients receiving placebo (p<0.001). Thirty-four percent of patients receiving SIMPONI whose prior anti-TNF-alpha therapy had been discontinued for all other reasons achieved ACR 20, compared with 20 percent of patients receiving placebo (p=0.027).

"Golimumab has shown promise in the treatment of rheumatoid arthritis patients who have previously discontinued other anti-TNF-alpha therapies," said Josef S. Smolen, MD, Professor and Chairman, Department of Rheumatology, Medical University of Vienna, Vienna, Austria, lead investigator. "Regardless of the reasons for discontinuation of prior anti-TNF-alpha agents, golimumab has demonstrated efficacy and tolerability, and provides hope for people struggling with rheumatoid arthritis."

Regardless of the particular anti-TNF-alpha agent previously used in treatment (adalimumab, etanercept or infliximab), the findings were consistent and showed SIMPONI to be effective in improving signs and symptoms of RA. Eighty percent of patients received prior anti-TNF-alpha therapy for at least 12 weeks and 49 percent received prior anti-TNF-alpha therapy for at least 48 weeks. At week 14, 32 percent of patients previously treated with adalimumab, 41 percent of patients previously treated with etanercept and 41 percent of patients previously treated with infliximab achieved ACR 20. At week 24, 34 percent, 44 percent and 48 percent of patients, respectively, achieved ACR 20. Patients also experienced significant improvement in disease activity at six months as measured by DAS28.

Investigators reported that the safety profile of SIMPONI among anti-TNF-alpha experienced patients in the GO-AFTER trial was similar to findings from two additional Phase 3 trials that evaluated SIMPONI in biologic-naive patients.

"The efficacy of SIMPONI demonstrated in this Phase 3 study is encouraging news for patients with moderately to severely active rheumatoid arthritis who have been previously treated with anti-TNF agents," said Robert J. Spiegel, MD, chief medical officer, Schering-Plough Research Institute. "The study demonstrates that every four-week subcutaneous injections of golimumab may benefit these patients by reducing the signs and symptoms of rheumatoid arthritis."

About the GO-AFTER Trial

GO-AFTER is the first placebo-controlled, double-blind, Phase 3 registration trial that demonstrates the efficacy and safety of an anti-TNF-alpha agent in patients previously treated with other anti-TNFs. The trial included 461 patients with active RA of 8.65 years mean duration. Discontinuation of previous anti-TNF-alpha therapy was to occur at least 8 to 12 weeks prior to enrollment in the study. Reasons for discontinuation of prior anti-TNF agent included lack of efficacy (58 percent), intolerance (17 percent), and other reasons (40 percent). Patients were randomized to one of three treatment groups: subcutaneous placebo, SIMPONI 50 mg or SIMPONI 100 mg every four weeks. (The approved dose in the US and Canada is 50 mg administered by subcutaneous injection once a month.) At baseline, 66 percent of patients were receiving methotrexate; 5 percent and 8 percent of patients were receiving sulfasalazine and hydroxychloroquine, respectively. Patients continued to receive stable doses of methotrexate, sulfasalazine and/or hydroxychloroquine if receiving them at baseline.

Subgroup analyses were performed for ACR 20 response at week 14 across disease-modifying anti-rheumatic drug use, number of prior anti-TNF-alpha agents and reason for discontinuation of prior TNF inhibitor. Ninety-five percent confidence intervals were calculated comparing the proportions of ACR 20 responders at week 14 in the combined SIMPONI vs. placebo groups. A subset of patients receiving a single prior anti-TNF-alpha agent was also examined to assess the impact of TNF inhibitor types (P75 receptor-fusion protein versus monoclonal antibody) on SIMPONI response.

The occurrence of adverse events (AEs) through week 24 was similar among patients previously receiving only adalimumab (76 percent), etanercept (70 percent) and infliximab (78 percent), as well as among patients who received one, two and three prior anti-TNF-alpha agents in both placebo (74 percent, 77 percent, 71 percent, respectively) and SIMPONI (75 percent, 70 percent, 77 percent respectively) treated patients. SIMPONI was generally well tolerated in this study. Through week 24, 72 percent, 66 percent and 78 percent of patients in the placebo, SIMPONI 50 mg and SIMPONI 100 mg groups, respectively, experienced at least one AE. Seven percent of patients in the placebo group experienced serious AEs, compared with 5 percent and 3 percent of patients in the SIMPONI 50 mg and SIMPONI 100 mg groups, respectively. Serious infections were reported in 3 percent, 3 percent and 1 percent of patients, and injection site reactions (ISR) through week 16 occurred in 3 percent, 4 percent and 11 percent of patients in the placebo, SIMPONI 50 mg and SIMPONI 100 mg groups, respectively. The most commonly reported ISR was erythema. No serious or severe ISRs were reported, and none led to the discontinuation of patients in the study. Antibodies to SIMPONI were detected in 4 percent of golimumab-treated patients (50 mg and 100 mg).

The GO-AFTER study was supported by Centocor Ortho Biotech Inc. and Schering-Plough Corporation.

About Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic and debilitating disease that affects approximately 1.3 million people in the United States and more than three million people in Europe. Signs and symptoms of RA include pain, stiffness and motion restriction in multiple joints. Because RA is a progressive disease, it can cause permanent joint deformity and severe disability if not diagnosed early or if initial treatment is delayed. RA can occur at any age, but is most common in adults 30-50 years old and is two to three times more prevalent in women than in men. The cause of RA is unknown, although genetic factors may contribute to the disease.

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 in the joints of people with rheumatoid arthritis. 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.

(This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could vary materially from Centocor Ortho Biotech Inc. and/or Johnson & Johnson's expectations and projections. Risks and uncertainties include general industry conditions and competition; economic conditions, such as interest rate and currency exchange rate fluctuations; technological advances and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approvals; domestic and foreign health care reforms and governmental laws and regulations; and trends toward health care cost containment. A further list and description of these risks, uncertainties and other factors can be found in Exhibit 99 of Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended December 28, 2008. Copies of this Form 10-K, as well as subsequent filings, are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. Neither Centocor Ortho Biotech Inc. nor Johnson & Johnson undertake to update any forward-looking statements as a result of new information or future events or developments.)

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.

SCHERING-PLOUGH DISCLOSURE NOTICE: The information in this press release includes certain "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including statements relating to the potential market for SIMPONI. Forward-looking statements relate to expectations or forecasts of future events. Schering-Plough does not assume the obligation to update any forward-looking statement. Many factors could cause actual results to differ materially from Schering-Plough's forward-looking statements, including market forces, economic factors, product availability, patent and other intellectual property protection, current and future branded, generic or over-the-counter competition, the regulatory process, and any developments following regulatory approval, among other uncertainties. For further details about these and other factors that may impact the forward-looking statements, see Schering-Plough's Securities and Exchange Commission filings, including Item 1A. "Risk Factors" in Schering-Plough's 2009 10-Q, filed May 1, 2009.

SOURCE Centocor Ortho Biotech Inc.

Source: PR Newswire

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