PARIS, France - 11 June 2008 Findings from two new Phase 3 studies showed that patients receiving every four-week subcutaneous injections of golimumab (CNTO 148) 50 mg and 100 mg and weekly methotrexate (MTX) experienced significant improvements in the signs and symptoms of rheumatoid arthritis (RA) as well as in physical function and disease activity, with some patients achieving remission as measured by Disease Activity Score (DAS28). Findings from two multicenter, randomized, double-blind, placebo-controlled Phase 3 studies showed the efficacy of golimumab in two important populations MTX-naive patients and patients with active RA despite ongoing treatment with MTX. These data were presented at the European League Against Rheumatism (EULAR) Annual Congress of Rheumatology. Golimumab is currently in the most comprehensive initial Phase 3 development program to date for an anti-tumor necrosis factor (TNF)-alpha biologic therapy with ongoing studies for the treatment of RA, psoriatic arthritis and ankylosing spondylitis.
In the study, GOlimumab FOR subjects With Active RA Despite MTX (GO-FORWARD), both the 50 mg and 100 mg doses of golimumab were studied in patients whose disease was active despite ongoing treatment with MTX. At week 14, 55 percent of patients receiving golimumab 50 mg plus MTX and 56 percent receiving golimumab 100 mg plus MTX achieved at least 20 percent improvement in signs and symptoms of RA (ACR 20), compared to 33 percent of patients receiving placebo and MTX (p<0.01 and p<0.001, respectively). Improvements were seen as early as first clinical assessment, which was four weeks after the first golimumab injection, and generally continued to improve over time.
"The data in this study demonstrate that golimumab is beneficial in improving numerous disease parameters, including inducing remission, in patients whose disease was active despite ongoing treatment with methotrexate," said Edward Keystone, M.D., FRCPC, director of the Rebecca MacDonald Centre for Arthritis & Autoimmune Disease at Mount Sinai Hospital in Toronto, and lead study investigator. "Since some patients do not respond adequately to methotrexate alone, this combination therapy could prove to be a highly valuable treatment option based on these results."
Patients receiving golimumab also experienced improvement in physical function as assessed by the Health Assessment Questionnaire (HAQ). At 24 weeks, 68 percent of patients in the golimumab 50 mg dosing group and 72 percent of patients receiving golimumab 100 mg experienced clinically relevant improvement in physical function (improvement in HAQ score of at least 0.25 from baseline), compared with 39 percent of patients receiving placebo plus MTX (p<0.0001). HAQ assess 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).
At week 14, 74 percent and 76 percent of patients in the golimumab 50 mg and 100 mg plus MTX groups, respectively, were classified as DAS28 (using C-reactive protein [CRP]) responders, compared with 52 percent of patients receiving MTX alone (p<0.001). Importantly, 35 percent and 32 percent of patients in the respective golimumab groups achieved remission based on DAS28 (CRP), compared with 13 percent of patients receiving placebo plus MTX (p<0.001). These improvements were sustained through six months.
In another Phase 3 study, GOlimumab Before Employing methotrexate as the First-line Option in the treatment of Rheumatoid arthritis of Early onset (GO-BEFORE), MTX-nave patients treated with golimumab 50 mg or 100 mg in combination with MTX experienced improvement in signs and symptoms of arthritis as well as in disease activity. The study's primary endpoint was based on an intent-to-treat (ITT) analysis, which included all patients randomized in the study. However, three patients did not receive study drug but were included in the analysis as nonresponders. In the primary analysis of the combined group of patients receiving either golimumab 50 mg or 100 mg in combination with MTX, 38 percent (40 percent receiving 50 mg and 37 percent receiving 100 mg) achieved at least 50 percent improvement in signs and symptoms of RA (ACR 50) through week 24, compared with 29 percent of patients receiving placebo plus MTX (p=0.053 for the combined group, p=0.042 for 50 mg and p=0.177 for 100 mg). When the three patients who did not receive golimumab were excluded in a modified intent-to-treat (mITT) analysis, the results showed that 39 percent of patients in the combined golimumab plus MTX group (41 percent receiving 50 mg and 37 percent receiving 100 mg) achieved ACR 50, compared with 29 percent of patients receiving placebo plus MTX (p=0.049 for the combined group, p=0.038 for 50 mg and p=0.177 for 100 mg). Additionally, 62 percent of patients in the combined golimumab plus MTX group (62 percent for each dose group) achieved ACR 20, compared with 49 percent receiving placebo plus MTX (p=0.011 for the combined group and p=0.028 for each dose group).
"These data show that treatment with golimumab induces an important depth of response, improving multiple aspects of rheumatoid arthritis and leading to significant decreases in disease activity," said Roy Fleischmann, M.D., Clinical Professor, Department of Internal Medicine at the University of Texas Southwestern Medical Center; Chief, Division of Rheumatology at St. Paul University Hospital in Dallas, Texas and lead study investigator. "Golimumab, which is an anti-TNF therapy, is a promising treatment option for multiple patient populations with this chronic and potentially debilitating inflammatory disease."
Also at week 24, patients receiving golimumab plus MTX experienced improvements in disease activity as measured by DAS28. Seventy-six percent of patients in the combined golimumab group were classified as DAS28 (CRP) responders, and 38 percent achieved DAS 28 remission, compared with 61 percent and 28 percent of patients receiving placebo and MTX, respectively (p<0.001 for responders and p=0.031 for remission).
"We are encouraged by the findings of both of these Phase 3 studies," said Robert J. Spiegel, M.D., chief medical officer, Schering-Plough Research Institute. "Golimumab holds great promise as an anti-TNF therapy for patients who may benefit from monthly subcutaneous injections for RA and related rheumatic diseases."
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.
|Contact: Brian Kenney|