Re: NEWS - FDA approves Orencia (abatacept) for rheumatoid arthritis

[Guest guest]

Even though we are all unlucky enough to be striken with this disease

(RA), at least we are lucky that it is one of the diseases that

someone is still working on! Maybe this will help alot of us!

Thanks!

>

> FDA Approves Orencia® (abatacept) For Rheumatoid Arthritis Treatment

>

> Category: Arthritis News

> Article Date: 26 Dec 2005

>

>

> Bristol-Myers Squibb Company (NYSE: BMY) 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

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.

>

>

> Orencia Prescribing Information

> http://www.orencia.com

>

>

> 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.

>

>

> 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 swelling1. 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 population2, including

more than

> two million people in the United States3. 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.

> Accessed December 20, 2005.

>

>

> http://www.medicalnewstoday.com/medicalnews.php?newsid=35382

>

>

>

>

> Not an MD

>

> I'll tell you where to go!

>

> Mayo Clinic in Rochester

> http://www.mayoclinic.org/rochester

>

> s Hopkins Medicine

> http://www.hopkinsmedicine.org

>