Bristol-Myers Squibb Company (NYSE: BMY) today announced that two-year data from three Phase III pivotal trials demonstrate the long-term efficacy of ORENCIA? (abatacept) in adult patients with moderate to severe rheumatoid arthritis (RA) who have had an inadequate response to one or more disease-modifying anti-rheumatic drugs (DMARDs) such as methotrexate and TNF antagonists. The data also demonstrate that ORENCIA provided clinically meaningful improvements in multiple aspects of health-related quality of life and physical function, sustained improvements in pain and had a consistent safety and tolerability profile through two years of treatment. These data will be presented at the upcoming 2006 American College of Rheumatology (ACR) Annual Scientific Meeting.
The findings are from analyses of the ongoing open-label, long-term extension component of Phase III pivotal trials investigating ORENCIA, including the AIM (Abatacept in Inadequate responders to Methotrexate), ATTAIN (Abatacept Trial in Treatment of Anti-TNF Inadequate Responders) and ASSURE (Abatacept Study of Safety in Use with other Rheumatoid Arthritis Therapies) trials.
“These data are encouraging and add to the body of evidence demonstrating that ORENCIA is an effective option providing durable response for patients who have not benefited fully from previous treatment with disease-modifying anti-rheumatic drugs,” said Mark Genovese, M.D., associate professor of medicine at Stanford University School of Medicine, Palo Alto, CA, who is presenting data from ATTAIN at the ACR meeting. “Given that rheumatoid arthritis is a chronic disease, long-term data such as these are important and offer physicians additional insight to help them make the most appropriate treatment decisions for their patients.”
Details of Data to be Presented
Two separate poster presentations evaluating two-year, open-label, long-term extension data from the AIM (Abatacept in Inadequate responders to Methotrexate) and ATTAIN (Abatacept Trial in Treatment of Anti-TNF Inadequate Responders) trials will be presented at the ACR Annual Scientific Meeting in Washington, DC. These include Dougados, et al, to be presented on Sunday, November 12, Poster No. 502, and Luggen, et al, to be presented on Monday, November 13, Poster No. 980.
Results from the study presented by Dougados showed a sustained improvement in pain for both the AIM and ATTAIN populations receiving ORENCIA? (abatacept) through two years. The mean change in baseline at one year was -35.5 for the ORENCIA arm of the AIM group (n=376) and -24.1 for the placebo group (n=160). At two years, the mean change in baseline for those receiving ORENCIA was -37.7. The mean change in baseline at six months was -30.8 for the ORENCIA arm of the ATTAIN group (n=217) and -10.2 for the placebo group (n=99). At two years, the mean change in baseline for those receiving ORENCIA was -37.2.
The study presented by Luggen showed sustained improvements in physical function for both the AIM and ATTAIN populations through two years as assessed using the Health Assessment Questionnaire Disability Index (HAQ-DI). HAQ-DI was assessed for the intent-to-treat (ITT) population, using a last observation carried forward (LOCF) analysis. Responders were defined as those achieving a change of greater than or equal to 0.3 HAQ-DI units from baseline. In the AIM group, 71.8 percent were HAQ responders at year one and 66.8 percent were HAQ responders at year two. In the ATTAIN group, 54.4 percent were HAQ responders at six months and 47.9 percent were HAQ responders at two years.
A separate analysis of the two-year ATTAIN trial (Genovese, et al) will be presented on Sunday, November 12, 2006, Poster No. 498. Of the 258 patients originally treated with ORENCIA during the double-blind phase, 218 entered an open-label, long-term extension (LTE), with 156 of these completing 2 years of the study. Data, analyzed using an LOCF analysis (all patients who entered the LTE, with discontinued patients considered as non-responders), demonstrated sustained efficacy over time in the ATTAIN population. At six months, ACR 20, 50 and 70 scores were achieved in 59.4 percent, 23.5 percent and 11.5 percent, respectively, in those treated with ORENCIA. At two years, ACR 20, 50 and 70 scores were achieved in 56.2 percent, 33.2 percent and 16.1 percent, respectively, of those completing two years of treatment with ORENCIA)R)(abatacept)..
Two-year data from ASSURE (Abatacept Study of Safety in Use with other Rheumatoid Arthritis Therapies; Weinblatt, et al) will be presented on Sunday, November 12, 2006, Poster No. 509. According to the results, ORENCIA? (abatacept) plus background non-biologic therapies demonstrated a consistent safety profile through two years. At year one, the incidence rate for Serious Adverse Events (SAEs) per 100 patient years (n=957 patient years) was 18.8 and 491.4 for Adverse Events (AEs). At year two, the incidence rate for SAEs per 100 patient years (n=1292 patient years) was 18.6 and 362.8 for AEs. During the open-label period, most discontinuations were due to AEs (3.3 percent), withdrawal of consent (2.5 percent) and lack of efficacy (2.4 percent).
ORENCIA is indicated for reducing signs and symptoms, inducing major clinical response, slowing the progression of structural damage, and improving physical function in adults with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more DMARDs, such as methotrexate or 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.
ORENCIA, a selective co-stimulation modulator of a signal required for full T-cell activation, was discovered and developed by Bristol-Myers Squibb Company.
Important Safety Information About ORENCIA
Before receiving treatment with ORENCIA, individuals should notify their healthcare providers if they currently are receiving treatment with a TNF antagonist (e.g., Enbrel?, Humira?, Remicade?) or Kineret? to treat RA. These individuals may have a higher risk of experiencing serious infections if they receive treatment with ORENCIA together with other biologic medications for RA. People receiving treatment with ORENCIA also should notify their healthcare providers if they are taking any other medications including hormones, over-the-counter medicines, vitamins, supplements or herbal products.
Individuals should discuss their risks of infection with their healthcare providers. People should inform their healthcare providers of any infections that they may have, including infections in a specific location in or on the body (such as an open cut or sore), or an infection that involves the whole body (such as the flu), as these types of infection could put individuals at risk for serious side effects from ORENCIA. Additionally, individuals should alert their healthcare providers if they have infections that won’t heal or have histories of recurring infections.
People who have had tuberculosis (TB), have had a positive skin test for TB, or who recently have been in close contact with someone who has had TB should inform their healthcare providers. If these individuals develop any of the symptoms of TB (i.e., a dry cough that doesn’t improve, weight loss, fever, night sweats, etc.), they should notify their healthcare providers immediately. Before initiating treatment with ORENCIA? (abatacept), healthcare providers may examine individuals for TB or perform a skin test to determine the presence of TB.
Additionally, individuals should inform their healthcare providers if they are scheduled to have surgery, or if they recently received a vaccination or are scheduled to receive any vaccinations. Before receiving ORENCIA, people should alert their healthcare providers if they have a history of chronic obstructive pulmonary (lung) disease (COPD), as taking ORENCIA may cause their COPD symptoms to worsen.
Pregnant women, women planning to get pregnant or women thinking about becoming pregnant should inform their healthcare providers prior to starting treatment with ORENCIA. It is not known if exposure to ORENCIA poses risks to unborn infants. Women should alert their healthcare providers if they are breastfeeding, as these individuals will need to decide either to breastfeed or to receive treatment with ORENCIA, but not both.
Like all medicines that affect the immune system, ORENCIA can cause serious side effects, including serious infections, allergic reactions and malignancies. Individuals receiving treatment with ORENCIA are at increased risk for developing infections including pneumonia and other infections caused by viruses, bacteria or fungi. Individuals should immediately contact their healthcare providers if they feel sick or experience any infection during treatment with ORENCIA. Allergic reactions to ORENCIA therapy may also occur. These reactions are usually mild or moderate, generally occur within the first 24 hours of an infusion and can include hives, swollen face, eyelids, lips, tongue, throat or difficulty breathing. There have been two serious allergic reactions reported in individuals following ORENCIA infusion. There have also been cases of certain kinds of cancer in individuals receiving ORENCIA. The role of ORENCIA in the development of cancer is not known.
The more common side effects with ORENCIA are headache, upper respiratory tract infection, sore throat and nausea.
For full prescribing information, please visit http://www.orencia.com/ or http://www.bms.com/.
Dosing and Administration
ORENCIA? (abatacept) is administered as a 30-minute intravenous infusion at a fixed dose based on body weight range approximating 10 mg/kg at day 0, 2 weeks, 4 weeks, and every 4 weeks thereafter. Acute infusion-related reactions were experienced in nine percent of patients treated with ORENCIA? (abatacept) and in six percent of patients treated with placebo. According to the full prescribing information, the most frequently reported infusion- related adverse events (1 percent to 2 percent) were dizziness, headache, and hypertension. In pivotal studies, 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.
The Role of T Cells in Rheumatoid Arthritis
In those patients with autoimmune diseases like RA, the immune system mistakes the body’s own cells for a foreign invader and launches an attack.
One type of cell found within the immune system is a T cell. When T cells are activated, it is thought that they may start a chain of events that leads to the inflammation, pain and joint damage of RA. ORENCIA works at the T-cell level, blocking one of the signals that causes a T cell to become fully active. By doing so, ORENCIA helps modulate the downstream activity of B cells, dendritic cells, macrophages and other cells involved in the RA inflammatory cascade.
This is different than other biologic therapies, which work at the cytokine level of the immune system process. Cytokines are a class of proteins that are mostly produced by immune system cells, including T cells. Some cytokines are thought to have primary roles in the development of RA.
About Rheumatoid Arthritis
Rheumatoid arthritis 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. RA causes limited range of motion and decreased function as a result of affected joints losing their shape and alignment.
RA affects about 1 percent of the world’s population, including more than two million people in the United States. The condition is more common in women, who account for 70 percent of patients diagnosed with RA.
Bristol-Myers Squibb is a global pharmaceutical and related health care products company whose mission is to extend and enhance human life.