PRINCETON, N.J., Dec. 23 /PRNewswire-FirstCall/-- Bristol-Myers Squibb Company (NYSE: BMY - News) announced today that the U.S. Food and Drug Administration (FDA) has approved ORENCIA® (abatacept), the first selective modulator of a co-stimulatory signal required for full T-cell activation, for the treatment of rheumatoid arthritis (RA).
ORENCIA is indicated for reducing the signs and symptoms of RA, inducing major clinical response, slowing the progression of structural damage, and improving physical function in adult patients with moderately to severely active RA who have had an inadequate response to one or more disease-modifying anti-rheumatic drugs (DMARDs), such as methotrexate (MTX) or tumor necrosis factor (TNF) antagonists. ORENCIA may be used as monotherapy or concomitantly with DMARDs other than TNF antagonists. ORENCIA should not be administered concomitantly with TNF antagonists and is not recommended for use concomitantly with anakinra.
"Bristol-Myers Squibb is committed to discovering and developing innovative medications that address areas of significant unmet need," said Peter R. Dolan, chief executive officer, Bristol-Myers Squibb. "There is clearly a need for more therapies for rheumatoid arthritis, and ORENCIA has the potential to help many people with this serious disease. ORENCIA is our first internally-discovered biologic and it further diversifies our pharmaceutical portfolio."
ORENCIA was studied in patients with an inadequate response to DMARDs. Specifically, it is the first approved agent to demonstrate efficacy and safety in patients with an inadequate response to TNF antagonists, as well as those with an inadequate response to MTX. Methotrexate is the most widely used non-biologic DMARD for RA and TNF antagonists are the most widely used biologic therapies for RA. ORENCIA is also the first in a new class of agents for the treatment of RA that selectively modulates a co-stimulatory signal required for full T-cell activation.
"In clinical trials, ORENCIA significantly reduced the signs and symptoms of rheumatoid arthritis among patients who had inadequate response to DMARDs such as methotrexate and/or anti-TNF therapy when compared to placebo," said Mark Genovese, M.D., associate professor of medicine at the Stanford University School of Medicine, Palo Alto, CA. "Rheumatoid arthritis is a very serious disease and it is critical that we continue to add therapies to our armamentarium."
ORENCIA Clinical Development Program
The efficacy and safety profiles of ORENCIA have been studied through a rigorous clinical trial program that included more than 2,600 patients. More than 3,800 person-years of experience were included across the placebo- controlled and open-label extension periods of the clinical trials.
The Phase III trial program included three major double-blind randomized placebo-controlled studies: AIM (Abatacept in Inadequate responders to Methotrexate), which compared ORENCIA in combination with MTX to MTX alone; ATTAIN (Abatacept Trial in Treatment of Anti-TNF INadequate responders), which compared ORENCIA in combination with non-biologic DMARDs to non-biologic DMARDs alone in patients with an inadequate efficacy response to the TNF antagonists etanercept and infliximab; and ASSURE (Abatacept Study of Safety in Use with other RA thErapies), which studied the safety of ORENCIA compared to placebo when used in combination with a variety of biologic and non- biologic DMARDs.
In both pivotal Phase III efficacy studies (AIM and ATTAIN), ORENCIA demonstrated significant and sustained improvement of the signs and symptoms of RA as measured by American College of Rheumatology (ACR) 20, 50, and 70 scores, with significant difference from placebo by day 15 for ACR 20 in some patients, which was the first follow-up visit after the first dose. In both trials, significant improvements in physical function were noted as compared to placebo. Health-related quality of life was assessed by the SF-36 questionnaire; improvements were observed in the patients treated with ORENCIA as compared to placebo in all eight domains(*) of the SF-36. ACR responses and improvements in physical function were maintained up to three years in a Phase II trial of patients with inadequate response to MTX.
Additionally, a significant proportion of patients taking ORENCIA plus MTX achieved a major clinical response, defined as maintaining an ACR 70 score for six consecutive months, compared to those treated with MTX alone in AIM (14 percent versus 2 percent; p-value less than 0.001).
In AIM, structural damage was slowed in patients treated with ORENCIA plus MTX, compared to those treated with MTX alone.
Important Safety Information about ORENCIA
Concurrent therapy with ORENCIA and a biologic DMARD is not recommended. In controlled clinical trials, patients receiving concomitant ORENCIA and TNF antagonist therapy experienced more infections (63 percent) and serious infections (4.4 percent) compared to patients treated with only TNF antagonists (43 percent and 0.8 percent, respectively), without an important enhancement of efficacy.
Caution should be exercised in patients with a history of infection or underlying conditions which predispose them to infections. Treatment with ORENCIA should be discontinued if a patient develops a serious infection. Patients should be screened for tuberculosis and if positive, should be treated with standard medical practice prior to therapy with ORENCIA.
Less than 1 percent of patients treated with ORENCIA experienced hypersensitivity reactions, including two cases of anaphylaxis or anaphylactoid reactions. Other events potentially associated with drug hypersensitivity, such as hypotension, urticaria, and dyspnea, each occurred in less than 0.9 percent of patients treated with ORENCIA and generally occurred within 24 hours of an infusion with ORENCIA. Appropriate medical support measures for the treatment of hypersensitivity reactions should be available.
Live vaccines should not be given concurrently with ORENCIA or within three months of its discontinuation.
Chronic obstructive pulmonary disease (COPD) patients treated with ORENCIA developed adverse events more frequently than those treated with placebo, including COPD exacerbations, cough, rhonchi, and dyspnea. Use of ORENCIA in patients with rheumatoid arthritis and COPD should be undertaken with caution and such patients should be monitored for worsening of their respiratory status.
ORENCIA should be used during pregnancy only if clearly needed. Rats treated every three days with abatacept during early gestation throughout the lactation period showed no adverse effects in the offspring at doses up to 45 mg/kg. At a dose of 200 mg/kg, alterations of immune function consisted of a 9-fold increase in the T-cell dependent antibody response in female pups and inflammation of the thyroid in one female out of 10 male and 10 female pups evaluated. Whether these findings indicate a risk for development of autoimmune diseases in humans exposed in utero to abatacept has not been determined.
Nursing mothers should discuss with their healthcare practitioner the risk/benefit of continued breast-feeding or discontinuation of the drug.
The most serious adverse reactions were serious infections (3 percent ORENCIA versus 1.9 percent placebo) and malignancies (1.3 percent ORENCIA versus 1.1 percent placebo).
The overall frequency of malignancies was similar in patients treated with ORENCIA and placebo-treated patients. However, more cases of lung cancer were observed in patients treated with ORENCIA (0.2 percent) than placebo-treated patients (0 percent). A higher rate of lymphoma was seen compared to the general population; however, patients with RA, particularly those with highly active disease, are at a higher risk for the development of lymphoma. The potential role of ORENCIA in the development of malignancies in humans is unknown.
The most frequent adverse events occurring in greater than or equal to 10 percent of patients treated with ORENCIA were headache, upper respiratory tract infection, nasopharyngitis, and nausea.
For full prescribing information, please visit www.orencia.com or www.bms.com, or call toll-free 1-800-ORENCIA (673-6242).
Dosing and Administration
ORENCIA (a fully human soluble fusion protein) is administered as a 30-minute intravenous infusion at a fixed dose based on weight range approximating 10 mg/kg at day 0, 2 weeks, 4 weeks, and every four weeks thereafter. Infusion reactions were experienced in 9 percent of patients treated with ORENCIA and in 6 percent of patients treated with placebo. The most frequently reported events (1 percent to 2 percent) were dizziness, headache, and hypertension. In clinical trials, premedications were not required. However, appropriate medical support measures for the treatment of hypersensitivity reactions should be available for immediate use in the event of a reaction.
ORENCIA Supply Information
ORENCIA is expected to be available for initial commercial use by the end of February 2006. As previously stated, in order to increase production capacity and meet expected long-term demand for ORENCIA, Bristol-Myers Squibb expects to submit a supplemental biologics license application (sBLA) to the FDA for a third-party manufacturing facility shortly. During this period between BLA and sBLA approval, a single distributor will be used. For more information, healthcare providers and patients can call 1-800-ORENCIA (673-6242) or visit www.orencia.com or www.bms.com.
Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a systemic, chronic, autoimmune disease characterized by inflammation in the lining of joints (or synovium), causing joint damage with chronic pain, stiffness, and swelling(1). RA causes limited range of motion and decreased function as a result of affected joints losing their shape and alignment(1).
RA affects about 1 percent of the world's population(2), including more than two million people in the United States(3). The condition is more common in women than in men, who account for 75 percent of patients diagnosed with RA(3).
Bristol-Myers Squibb is a global pharmaceutical and related health care products company whose mission is to extend and enhance human life.
Bristol-Myers Squibb Forward Looking Statement
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding ORENCIA supply. 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. There can be no guarantee that the sBLA for a second ORENCIA manufacturing facility will be approved. 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, 2004 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.
(*) The eight domains are: physical functioning, role-limitations due to physical problems, energy/fatigue, emotional well-being, role- limitations due to emotional problems, social functioning, pain and general health.
(1) Guidelines for the management of rheumatoid arthritis; 2002 update. Arthritis & Rheumatism. 2002;46(2):328-346. (2) Lee DM and Weinblatt ME. Rheumatoid arthritis. Lancet. 2001;358:903-911. (3) American College of Rheumatology Web site. Rheumatoid arthritis.
http://www.rheumatology.org/public/factsheets/ra_new.asp?aud=pat#3 Accessed December 20, 2005.
Source: Bristol-Myers Squibb Company
