WASHINGTON, Nov. 13 /PRNewswire/ -- Nearly 75 percent of patients with moderately to severely active rheumatoid arthritis (RA) receiving golimumab (CNTO 148) and methotrexate experienced at least 20 percent improvement in arthritis symptoms (ACR 20) at week 52, according to new findings presented from a double-blind, placebo-controlled, dose-ranging Phase 2 study. Investigators also reported that more than one-third of patients treated with golimumab and methotrexate achieved remission at one year, as evaluated by Disease Activity Score 28 (DAS28) [DAS < 2.6]. Golimumab, Centocor, Inc. and Schering-Plough’s next generation biologic therapy is a fully-human anti-TNF- alpha monoclonal antibody that targets and neutralizes both the soluble and the membrane-bound form of TNF-alpha. Golimumab is being investigated for administration by subcutaneous (SC) injection and intravenous (IV) infusion.
“In preliminary 16 week study findings, golimumab reduced the signs and symptoms and induced remission in patients with rheumatoid arthritis,” said Jonathan Kay, MD, Director of Clinical Trials, Rheumatology Unit, Massachusetts General Hospital, Associate Clinical Professor of Medicine, Harvard University School of Medicine, and lead study investigator. “These data show that the therapeutic effect was maintained, which is promising for this investigational therapy.”
Data from the study showed that significantly more patients in all groups receiving SC injections of golimumab plus methotrexate achieved ACR 20, 50, 70 responses (marked improvement in arthritis symptoms according to the American College of Rheumatology scoring criteria) versus patients receiving placebo plus methotrexate through 16 weeks (the primary endpoint of the study). Adults with active RA for at least three months’ duration despite methotrexate therapy were randomized to one of five treatment groups: placebo every two weeks or golimumab 50 or 100 mg every two weeks or every four weeks. All patients received stable doses of methotrexate of at least 10 mg/week. At week 16, 62 percent, 31 percent and 12 percent of all patients receiving golimumab (combined golimumab treatment groups) plus methotrexate experienced ACR 20, ACR 50 and ACR 70 improvements, respectively, compared with 37 percent, 6 percent and zero percent of patients receiving placebo plus methotrexate, respectively (all P < 0.05). At week 52 of the study, ACR 20, ACR 50 and ACR 70 scores improved to 74 percent, 45 percent and 22 percent respectively, among patients receiving golimumab plus methotrexate (combined golimumab treatment groups). Moreover, patients receiving 50 mg every two weeks and 100 mg every two weeks maintained efficacy through week 52, even after converting to every four weeks administration at week 20.
Patients receiving golimumab plus methotrexate also achieved remission, as assessed by DAS 28, which measures tender and swollen joints, inflammation and overall disease activity including measurement of serum C-reactive protein (CRP) levels. After 16 weeks of treatment, 27 percent of patients in the golimumab (combined golimumab treatment groups) plus methotrexate group achieved remission as assessed by DAS28 (DAS < 2.6) compared with six percent of patients receiving placebo plus methotrexate (P < 0.05). Similar remission rates were reported at week 52, with 34 percent of patients receiving golimumab plus methotrexate achieving remission at that time point.
About the Study
This Phase 2, randomized, double-blind, placebo-controlled, dose-ranging trial involved 172 patients with active rheumatoid arthritis for at least three months’ duration despite methotrexate therapy. Patients were randomized to one of five treatment groups and beginning at week 20, patients randomized to the placebo group received infliximab (3 mg/kg) at weeks 20, 22, 28, 36, and 44. Patients receiving golimumab continued at their assigned dose (50 or 100 mg) every four weeks from week 20 to week 48.
Golimumab was generally well tolerated in the study through week 52. Serious adverse events (AEs) reported prior to crossover at week 20 were eight percent for the combined golimumab groups compared with six percent for the placebo group. After crossover from weeks 20 to 52, serious AEs were nine percent in the combined golimumab groups, compared to 12 percent in the infliximab group. No deaths, cases of tuberculosis or other opportunistic infections were reported through 52 weeks, and serious infections were uncommon. The most common clinically relevant serious AEs through week 52 were pneumonia (three patients), lung cancer (one patient), cardiac tamponade (one patient), and cardiac failure (one patient). One patient died from coronary artery disease approximately four months after completing 52 weeks of the study.
About Rheumatoid Arthritis
RA is a chronic, progressive disease and research suggests that a critical therapeutic window may exist within the first two years of disease onset when the rate of radiographic progression of the disease can be “reset."(1, 2, 3) Radiographic changes occur within two years of disease onset in 50-70 percent of RA patients.(4) The American College of Rheumatology (ACR) suggests control of disease progression should start early to limit joint damage in RA.(3) RA is associated with substantial disability and economic losses, and one study showed that one-third of patients in the UK who were employed became work-disabled within two years of disease onset.(5) Rheumatologic disorders also account for 25 percent of Social Security disability payments.(6)
About Centocor
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, Inc. 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 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 January 1, 2006. Copies of this Form 10-K, as well as subsequent filings, are available online at http://www.sec.gov or on request from Johnson
& Johnson. Johnson & Johnson does not undertake to update any forward-looking statements as a result of new information or future events or developments.
About Schering-Plough
Schering-Plough is a global science-based health care company with leading prescription, consumer and animal health products. Through internal research and collaborations with partners, Schering-Plough discovers, develops, manufactures and markets advanced drug therapies to meet important medical needs. Schering-Plough’s vision is to earn the trust of the physicians, patients and customers served by its more than 32,000 people around the world. The company is based in Kenilworth, N.J., and its Web site is http://www.schering-plough.com.
SCHERING-PLOUGH DISCLOSURE NOTICE: The information in this press release contains certain “forward-looking” statements within the meaning of the Securities Reform Act of 1995, including statements related to REMICADE and the potential market for REMICADE. 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, current and future branded, generic or over-the-counter competition and the regulatory process, among other uncertainties. For further details and a discussion of risks and uncertainties that may affect forward- looking statements, see the company’s Securities and Exchange Commission filings, including the company’s second quarter 2006 10-Q.
References: (1) Landewe RB, Boers M, Verhoeven AC, et al. COBRA combination therapy in patients with early rheumatoid arthritis: long-term structural benefits of a brief intervention. Arthritis Rheum. 2002;46:347-356. (2) Egsmose C, Lund B, Borg G, et al. Patients with rheumatoid arthritis benefit from early 2nd line therapy: 5 year follow up of a prospective double blind placebo controlled study. J. Rheumatol. 1995;22:2208- 2213. (3) American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines, 2002 Update. (4) van der Heijde DM. Joint erosions and patients with early rheumatoid arthritis. Br J Rheumatol. 1995;34(suppl 2):74-78. (5) Barrett EM, Scott DGI, Wiles NJ, Symmons DPM. The impact of rheumatoid arthritis on employment status in the early years of disease: a UK community-based study. Rheumatology. 2000;39:1403-1409. (6) Social Security Disability Insurance Program.
Centocor, Inc.
CONTACT: Michael Parks of Centocor, Inc., +1-215-325-4010, or Mobile:+1-215-983-8000; or Cathy Cantone, +1-908-298-3944, or Mobile:+1-908-327-3013, or Alex Kelly, Investor Contact, +1-908-298-7436, both ofSchering-Plough
Web site: http://www.schering-plough.com/
