Healthcare Industry News: Methotrexate
News Release - June 11, 2008
Phase 3 Data Show Efficacy of Golimumab in Patients with Active Rheumatoid Arthritis Previously Treated with Anti-TNF AgentsStudy Demonstrated a Significant Reduction in the Signs and Symptoms of RA and Improved Physical Function
PARIS, June 11 (HSMN NewsFeed) -- Findings presented for the first time from a novel, randomized, double-blind, placebo-controlled Phase 3 study showed that patients with moderately-to-severely active rheumatoid arthritis (RA) who were previously treated with anti-tumor necrosis factor (TNF)-alpha agents, experienced significant improvements in signs and symptoms and physical function after receiving every four-week subcutaneous injections of golimumab (CNTO 148) 50 mg or 100 mg. Investigators also reported that the patients who received golimumab showed sustained improvements in disease activity and physical function through six months. The study was presented at the European League Against Rheumatism (EULAR) Annual Congress of Rheumatology.
"Our findings show that golimumab holds great promise in various RA patient populations, including those patients who have previously discontinued other TNF inhibitors," said Josef S. Smolen, M.D., professor and Chairman, Department of Rheumatology, Medical University of Vienna and lead study investigator. "Golimumab may provide an appropriate treatment option to the many people facing the consequences of this debilitating disease."
In the study, GOlimumab After Former anti-TNF Therapy Evaluated in RA (GO-AFTER), 35 percent and 38 percent of patients receiving golimumab 50 mg and 100 mg, respectively, achieved the primary endpoint of at least 20 percent improvement in arthritis symptoms (ACR 20) at week 14, compared with 18 percent of patients receiving placebo (p<0.001). These results were maintained through six months. Importantly, among the 58 percent of patients whose prior anti-TNF-alpha therapy had been discontinued due to lack of efficacy, 36 percent receiving golimumab 50 mg and 43 percent receiving golimumab 100 mg achieved ACR 20 as compared to 18 percent of patients treated with placebo (p=0.006 for 50 mg group, p<0.001 for 100 mg group, respectively). Patients in each study group continued to receive stable doses of Methotrexate (MTX), sulfasalazine (SSZ) and/or hydrochloroquine (HCQ) if they were receiving them at baseline.
"When treating patients with progressive rheumatoid arthritis, our goal is to reduce pain and improve physical function," said Jonathan Kay, M.D., Director, Clinical Trials, Rheumatology Unit, Massachusetts General Hospital; Associate Clinical Professor of Medicine, Harvard Medical School and lead study investigator. "We are encouraged by the results of these trials which suggest that golimumab may offer a significant benefit to a growing population of RA patients with prior TNF inhibitor experience."
Patients in both treatment groups receiving golimumab also experienced significant improvement in physical function and disease activity through six months as measured by the Health Assessment Questionnaire (HAQ) and the Disease Activity Score (DAS28), respectively. At 24 weeks, 52 percent of patients in the combined golimumab dosing group experienced a clinically relevant improvement in physical function (improvement in HAQ score of at least 0.25 from baseline), compared with 34 percent of patients receiving placebo (p<0.001). HAQ assesses the degree of difficulty a patient has in accomplishing tasks in eight functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping and other activities of daily living). Additionally, at six months, more than half of patients in the combined golimumab group were classified as DAS28 responders (using either C-reactive protein [CRP] or erythrocyte sedimentation [ESR] rate), compared with 23 percent and 25 percent of placebo-treated patients, respectively, indicating improvements in levels of disease activity.
Additionally, two separate Phase 3 studies, which were also presented at EULAR, evaluated golimumab in RA patients who had active RA despite MTX therapy (GO-FORWARD), and golimumab in RA patients who had not previously been treated with MTX (GO-BEFORE).
"Golimumab has the potential to benefit a broad range of patients by offering monthly subcutaneous treatment for RA," said Robert J. Spiegel, M.D., chief medical officer, Schering-Plough Research Institute. "These findings mark an important milestone for golimumab as we look forward to expanding the immunology franchise at Schering-Plough and remaining leaders in the rheumatology community."
In March 2008, Centocor Inc. and Schering-Plough Corporation (NYSE: SGP ) announced that a Marketing Authorization Application (MAA) had been submitted to the European Medicines Agency requesting the approval of golimumab as a monthly subcutaneous treatment for adults with RA, psoriatic arthritis and ankylosing spondylitis. The initial submission and Phase 3 development programs are unprecedented among anti-TNF-alpha therapies, as they mark the first time that an MAA has been proposed for review inclusive of three unique disease states. Golimumab, Centocor's and Schering-Plough's next-generation human anti-TNF-alpha monoclonal antibody, is being studied as an every four-week subcutaneous injection and an intravenous (IV) infusion therapy.
About the GO-AFTER Trial
The study, A Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Golimumab, a Human Anti-TNF Monoclonal Antibody, Administered Subcutaneously in Subjects with Active Rheumatoid Arthritis and Previously Treated with Biologic Anti-TNF-alpha Agent(s) (GO-AFTER) was a Phase 3, multi-center, double-blind trial that included 461 patients with active RA of 8.65 years mean duration. All patients had previously received at least one anti-TNF-alpha agent, with 25 percent (n=115) having been treated with two therapies and 9 percent (n=43) with three. Discontinuation of previous anti-TNF-alpha therapy was due to lack of efficacy (58 percent), intolerance (17 percent), and other reasons (40 percent). Patients were randomized to one of three treatment groups: SC placebo, golimumab 50 mg or golimumab 100 mg every four weeks. At baseline, 66 percent of patients were receiving MTX; 5 percent and 7 percent of patients were receiving SSZ and HCQ, respectively. Patients continued to receive stable doses of MTX, SSZ and/or HCQ if receiving them at baseline.
Golimumab was generally well tolerated in this study. Through week 24, 72 percent, 66 percent and 78 percent of patients in the placebo, golimumab 50 mg and golimumab 100 mg groups, respectively, experienced at least one adverse event (AE). Ten percent of patients in the placebo group experienced serious AEs, compared with 7 percent and 5 percent of patients in the golimumab 50 mg and golimumab 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, golimumab 50 mg and golimumab 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 golimumab were detected in 4 percent of golimumab-treated patients (50 mg and 100 mg).
Anti-TNF therapies have been associated with serious and sometimes fatal risks including the risk of TB and other serious infections, malignancies, heart failure, central nervous system disorders, reactivation of hepatitis B, and other serious events.
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.
Golimumab, Centocor Inc.'s and Schering-Plough Corporation's next-generation human anti-TNF-alpha monoclonal antibody, is currently in the most comprehensive Phase 3 development program to date for an anti-TNF-alpha biologic therapy. With ongoing studies for the treatment of RA, psoriatic arthritis and ankylosing spondylitis, golimumab is being studied as an every four week subcutaneous injection and an IV infusion therapy. Golimumab targets and neutralizes both the soluble and membrane-bound forms of TNF-alpha.
Centocor discovered golimumab and has exclusive marketing rights to the product in the United States. Pending regulatory approval, Schering-Plough will assume exclusive marketing rights outside the United States except in Japan, Indonesia and Taiwan where golimumab will be co-marketed by Mitsubishi Tanabe Pharma Corporation and Janssen Pharmaceutical Kabushiki Kaisha; Hong Kong, where golimumab will be exclusively marketed by Janssen-Cilag; and China where golimumab will be exclusively marketed by Xian-Janssen.
Centocor is harnessing the power of world-leading research and biomanufacturing to deliver innovative biomedicines that transform patients' lives. Centocor has already brought innovation to the treatment of Crohn's disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, ulcerative colitis, pediatric Crohn's disease and psoriasis.
The world leader in monoclonal antibody production and technology, Centocor has brought critical biologic therapies to patients suffering from debilitating immune disorders. Centocor is a wholly-owned subsidiary of Johnson & Johnson.
CENTOCOR DISCLOSURE NOTICE: 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'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 30, 2007. 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. Centocor does not undertake to update any forward-looking statements as a result of new information or future events or developments.
Schering-Plough 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 Golimumab. 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 Part I, Item IA. "Risk Factors" in Schering-Plough's 2008 Q1 10-Q.
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