Phase 3 data show efficacy of golimumab in RA patients previously treated with anti-TNF agents
Study demonstrated a significant reduction in the signs and symptoms of RA and improved physical function
PARIS, France - 11 June 2008 – 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.
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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. |
