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(R) (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(R) (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(R) (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(R), Humira(R), Remicade(R)) or Kineret(R) 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(R)
(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 ORENCIA or bms.
Dosing and Administration
ORENCIA(R) (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(R) (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.
Bristol-Myers Squibb Company
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View drug information on Orencia.
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