[ CTLA4Ig/BMY ]
Phase III Clinical Trial Results of Investigational Biologic Abatacept Demonstrated Clinical Activity in Patients With Rheumatoid Arthritis
Sunday October 17, 6:15 pm ET
SAN ANTONIO, Oct. 17 /PRNewswire-FirstCall/ -- According to the results of two phase III clinical trials to be presented this week at the annual meeting of the American College of Rheumatology (ACR), the investigational biologic abatacept (ab-a-'ta-sept) -- a potential first-in-class T-cell costimulation modulator discovered and developed by Bristol-Myers Squibb Company (NYSE: BMY - News) -- demonstrated significant clinical activity in patients with rheumatoid arthritis.
The studies focused on two different rheumatoid arthritis patient populations: either those who had not adequately responded to methotrexate or patients who did not adequately respond to tumor necrosis factor (TNF) inhibitors. As assessed by clinical measures, including disease progression, ACR response rate, physical function and quality of life, patients in both studies given abatacept in addition to therapy such as methotrexate showed improvements compared to those receiving placebo plus additional therapy.
Activated T cells in the body orchestrate the autoimmune response that leads to the joint inflammation and destruction as well as the disability often associated with rheumatoid arthritis. Abatacept selectively modulates one of the two signals needed for full T cell activation, thereby interrupting the inflammatory process.
A primary endpoint in each study was the proportion of patients achieving an ACR 20 response at six months, which is a way of determining patient improvement by examining multiple measures of disease activity. Patients recording an ACR 20 response have at least a 20 percent improvement in signs and symptoms of rheumatoid arthritis.
Abatacept was administered in a single 30-minute intravenous infusion on days 1, 15 and 29 of each study and every 28 days thereafter.
Abatacept in Inadequate Responders to Methotrexate (AIM) trial
The AIM trial, to be presented on Tuesday, October 19 at the ACR meeting, assessed efficacy and safety of abatacept for a period of 12 months in rheumatoid arthritis patients who inadequately responded to treatment with methotrexate. The progression of disease in the AIM trial, an additional primary endpoint, was also assessed and documented by radiographic evaluation.
In addition to methotrexate, a disease-modifying antirheumatic drug (DMARD), patients received either abatacept at a fixed dose approximating 10 mg/kg (385 patients) or a placebo (162 patients).
Through one year of abatacept treatment, 73.1% of patients on abatacept achieved an ACR 20 response compared to 39.7% on placebo. ACR 50 and ACR 70 responses in the abatacept group at one year (48.3% and 28.8%, respectively) exceeded what was observed in the placebo group (18.2% and 6.1%, respectively). The one-year results were statistically significant (p<0.001).
As a secondary endpoint, the signs and symptoms of rheumatoid arthritis were also assessed using an internationally recognized rating system known as the Disease Activity Score (DAS28). Among abatacept patients, 23.8% were in remission after one year, as defined by the DAS28 criteria, compared to 1.9% in the placebo group -- a statistically significant result (p<0.001).
Radiographic evaluation showed significant reductions in progression of joint erosions (p=0.029), joint space narrowing (p=0.009) and total score (p=0.012).
"The responses seen with abatacept increased through one year of treatment," said Joel Kremer, M.D., Director of Research at The Center for Rheumatology in Albany, N.Y. "These data confirm results from earlier studies and provide evidence for the potential benefit of targeting T-cell activation in rheumatoid arthritis treatment."
In the AIM trial, the incidence of adverse events was slightly higher with abatacept compared to placebo (87% vs. 84%, respectively). Abatacept had a low incidence of infusion reactions and serious infections, such as pneumonia, (3.9% for abatacept vs. 2.3% for placebo). The most common adverse events in the trial were headache, nasopharyngitis and nausea.
Abatacept Trial in Treatment of Anti-TNF Inadequate Responders (ATTAIN)
In ATTAIN, which will be presented at the ACR meeting on Thursday, October 21, researchers evaluated efficacy and safety of abatacept for a period of six months in patients with active rheumatoid arthritis and inadequate response to TNF inhibitors. Patients randomized in the trial had discontinued all TNF therapy.
In addition to at least one DMARD, patients received abatacept at a fixed dose approximating 10 mg/kg (258 patients) or a placebo (133 patients).
After six months of treatment, 50.4% of the patients on abatacept achieved ACR 20 responses compared to 19.5% on placebo. Additionally, 20.3% of patients in the abatacept group achieved ACR 50 and 10.2% achieved ACR 70. By contrast, 3.8% of the placebo group achieved ACR 50 and 1.5% reached ACR 70. The results observed in the abatacept group were statistically significant (p<0.001 for ACR 20 and 50; p<0.03 for ACR 70).
Remission rates were also measured as per the DAS28 scale, and 10% of abatacept patients achieved remission compared to 0.8% receiving placebo after 24 weeks of therapy. The remission results were statistically significant (p<0.001).
"Even in these patients who had already responded inadequately to a TNF therapy, half achieved an ACR 20 response with the abatacept therapy after six months," said Mark Genovese, M.D., Associate Professor of Medicine and Associate Chief of the Division of Immunology and Rheumatology at Stanford University.
In the ATTAIN trial, the incidence of adverse events was similar between abatacept and placebo. The incidence of serious infections was also similar (2.3% in each group). The most common adverse reactions were headache and nasopharyngitis.
About Rheumatoid Arthritis
One percent of the world's population has RA, accounting for more than 9 million physician visits and 250,000 hospitalizations in the United States annually. Three out of four patients diagnosed with RA are women.
About Bristol-Myers Squibb Company
Bristol-Myers Squibb Company is a global pharmaceutical and related health care products company whose mission is to extend and enhance human life.
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding product development. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Abatacept has not been submitted for regulatory approval. There can be no guarantee that abatacept will receive regulatory approval, or if approved, will be commercially successful. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol- Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2003 and in our Quarterly Reports on Form 10-Q. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. |
