Crohn's Disease Is The Fourth Autoimmune Disease For Humira Submitted For Regulatory Approval In Both The U.S. And Europe

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Crohn's Disease Is The Fourth Autoimmune Disease For Humira Submitted

For Regulatory Approval In Both The U.S. And Europe

10 Sep 2006

Abbott announced it has simultaneously submitted a supplemental

Biologics License Application (sBLA) with the U.S. Food and Drug

Administration (FDA) and a Type II Variation to the European

Medicines Agency (EMEA) seeking approval to market HUMIRA®

(adalimumab) as a treatment for moderate-to-severe Crohn's disease.

Crohn's disease is a serious, chronic inflammatory disease of the

gastrointestinal (GI) tract that affects more than one million people

in North America and Europe combined. Currently, there is no cure for

Crohn's disease, reinforcing the need for safe and effective

treatment options that will help patients maintain control of their

disease.

" HUMIRA may offer much-needed hope to physicians, as well as to

people living with Crohn's disease, who have had limited, effective,

long-term treatment options, " said Hanauer, M.D., Professor

of Medicine and Clinical Pharmacology Chief, Section of

Gastroenterology and Nutrition, University of Chicago.

The global filings are based on the results of three randomized,

double-blind, placebo-controlled, multi-center trials of HUMIRA -

CLASSIC I (CLinical assessment of Adalimumab Safety and efficacy

Studied as an Induction therapy in Crohn's disease), CHARM (Crohn's

trial of the fully Human antibody Adalimumab for Remission

Maintenance) and GAIN (Gauging Adalimumab effectiveness in Infliximab

Nonresponders).

Clinical trials have been completed evaluating the efficacy and

safety of HUMIRA in a range of moderate-to-severe Crohn's disease

patients, from those who were naïve to anti-TNF therapy to patients

who had previously lost response or were unable to tolerate

infliximab. In these trials, HUMIRA demonstrated statistical

significance in inducing and maintaining clinical remission in

patients with moderate-to-severe Crohn's disease. In the study

evaluating the ability of HUMIRA to maintain remission, a proportion

of patients in clinical remission were able to discontinue steroid use.

About HUMIRA Pivotal Crohn's Disease Clinical Trials

-- CLASSIC I was a study of 299 patients with moderate-to-severe

Crohn's disease, which showed that initiating treatment with HUMIRA

160 mg followed by 80 mg at week 2 resulted in a statistically

significant greater percentage of patients achieving clinical

remission at four weeks compared to placebo. Clinical remission was

defined as a Crohn's Disease Activity Index (CDAI) score of less than

150. CDAI is a weighted composite score of eight clinical factors

that evaluate patient wellness, including daily number of liquid or

very soft stools, severity of abdominal pain, level of general well-

being and other measures.

-- CHARM was a 56-week trial of patients with moderately-to-severely

active Crohn's disease. The 499 patients who demonstrated clinical

response to HUMIRA during a four-week open-label induction phase were

randomized to receive either HUMIRA or placebo. A statistically

significantly greater percentage of those who continued on HUMIRA

maintained clinical remission through one year compared to placebo.

In CHARM, the proportion of patients in clinical remission at week 26

and week 56 who were able to discontinue steroid use was evaluated.

At week 56, 29 percent of patients taking 40 mg HUMIRA every other

week and 23 percent of patients taking 40 mg HUMIRA weekly

discontinued the use of steroids and maintained remission, compared

to 6 percent of those receiving placebo (p< or = 0.008).

-- GAIN evaluated the efficacy of HUMIRA in moderately-to-severely

active Crohn's disease patients who had previously lost response or

were unable to tolerate infliximab, a group of patients currently

without effective treatment options. Results from GAIN will be

presented at the annual meeting of the American College of

Gastroenterology (ACG) and at the United European Gastroenterology

Week (UEGW) meeting, both in October.

The safety profile of HUMIRA in the Crohn's clinical trials was

similar to that seen in HUMIRA clinical trials for rheumatoid

arthritis (RA).

" Based on our clinical studies, we believe HUMIRA offers promise for

patients who suffer from Crohn's disease, " said Eugene Sun, M.D.,

vice president, Global Pharmaceutical Clinical Development at Abbott.

" Data from three pivotal studies in more than 1400 patients suggest

the potential of HUMIRA to help many Crohn's disease patients meet

their treatment goals of achieving and maintaining control of

symptoms and improving quality of life. "

About Crohn's Disease

Crohn's disease is a serious chronic, inflammatory disease of the GI

tract that may affect more than one million people in North America

and Europe combined and is typically diagnosed before age 40. It can

have a devastating impact on the lifestyles of patients, many of whom

are young and active. Common symptoms of the disease include

diarrhea, cramping, abdominal pain, weight loss, fever, and in some

cases, rectal bleeding. Complications include intestinal obstruction,

fistulas (ulcers that form tunnels to surrounding tissues), and

malnutrition. Over the course of their disease, at least 50 percent

of patients with Crohn's will undergo surgery at least once for

complications or disease refractory to treatment, and up to 70

percent of those patients may require a second surgery.

Abbott Initiates Additional Gastrointestinal Clinical Trials

Abbott has initiated a Treatment Protocol (CHOICE - Clinical study of

the Human antibody adalimumab in CrOhn's patients who failed prior

Infliximab: Collection of safety and Efficacy data) in the United

States to evaluate the use of HUMIRA in patients who are no longer

responding or are intolerant to infliximab, an approved therapy for

Crohn's disease. Treatment protocols are used to facilitate the

availability of promising new drugs under clinical investigation to

patients with a serious or life-threatening disease who are not

involved in the clinical trials and have no comparable or

satisfactory alternative drug or therapy available, and to obtain

additional data regarding use of the drug.

Additional information about HUMIRA clinical trials is available

through Abbott Medical Information, 1-800-633-9110.

Important Safety Information

Cases of tuberculosis (TB) have been observed in patients receiving

HUMIRA. Serious infections and sepsis, including fatalities, have

been reported with the use of TNF-blocking agents, including HUMIRA.

Many of these infections occurred in patients also taking other

immunosuppressive agents that in addition to their underlying disease

could predispose them to infections. Treatment with HUMIRA should not

be initiated in patients with active infections. TNF-blocking agents,

including HUMIRA, have been associated with reactivation of hepatitis

B (HBV) in patients who are chronic carriers of this virus. Some

cases have been fatal. Patients at risk for HBV infections should be

evaluated for prior evidence of HBV infections before initiating

HUMIRA. The combination of HUMIRA and anakinra is not recommended.

TNF-blocking agents, including HUMIRA, have been associated in rare

cases with demyelinating disease and severe allergic reactions.

Infrequent reports of serious blood disorders have been reported with

TNF-blocking agents. More cases of malignancies have been observed

among patients receiving TNF blockers, including HUMIRA, compared to

control patients in clinical trials. These malignancies, other than

lymphoma and non-melanoma skin cancer, were similar in type and

number to what would be expected in the general population. There was

an approximately four-fold higher rate of lymphoma in combined

controlled and uncontrolled open-label portions of HUMIRA clinical

trials. The potential role of TNF-blocking therapy in the development

of malignancies is not known.

The most frequent adverse events seen in the placebo-controlled

clinical trials in rheumatoid arthritis (HUMIRA vs. placebo) were

injection site reactions (20 percent vs. 14 percent), upper

respiratory infection (17 percent vs. 13 percent), injection site

pain (12 percent vs. 12 percent), headache (12 percent vs. 8

percent), rash (12 percent vs. 6 percent) and sinusitis (11 percent

vs. 9 percent). Discontinuations due to adverse events were 7 percent

for HUMIRA and 4 percent for placebo. As with any treatment program,

the benefits and risks of HUMIRA should be carefully considered

before initiating therapy.

About HUMIRA

HUMIRA is the only fully human monoclonal antibody approved by the

FDA for reducing signs and symptoms, inducing major clinical

response, inhibiting the progression of structural damage, and

improving physical function in adult patients with moderately-to-

severely active RA. HUMIRA can be used alone or in combination with

methotrexate (MTX) or other disease-modifying anti-rheumatic drugs

(DMARDs).

In the U.S., HUMIRA is also indicated for reducing the signs and

symptoms of active arthritis in patients with psoriatic arthritis.

HUMIRA can be used alone or in combination with DMARDs. HUMIRA was

also approved on July 28, 2006 for reducing signs and symptoms in

patients with active ankylosing spondylitis.

In Europe, HUMIRA, in combination with MTX, is indicated for the

treatment of moderate-to-severe, active RA in adult patients when the

response to DMARDs including MTX has been inadequate. HUMIRA is also

indicated for the treatment of severe, active and progressive RA in

adults not previously treated with MTX. HUMIRA can be given as

monotherapy in case of intolerance to MTX or when continued treatment

of MTX is inappropriate. HUMIRA has been shown to reduce the rate of

progression of joint damage as measured by X-ray and to improve

physical function when given in combination with MTX.

HUMIRA is indicated for the treatment of active and progressive

psoriatic arthritis in adults when the response to previous DMARD-

therapy has been inadequate. HUMIRA is also indicated for the

treatment of adults with severe, active ankylosing spondylitis who

have had an inadequate response to conventional therapy.

To date, HUMIRA has been approved in 67 countries, and more than

160,000 people worldwide are currently being treated with HUMIRA.

Clinical trials are currently under way evaluating the potential of

HUMIRA in other immune-mediated diseases.

Abbott's Commitment to Immunology

Abbott is focused on the discovery and development of innovative

treatments for immunologic diseases. The Abbott Bioresearch Center,

founded in 1989 in Worcester, Massachusetts, United States, is a

world-class discovery and basic research facility committed to

finding new treatments for autoimmune diseases. More information

about Abbott Immunology and HUMIRA, including full prescribing

information, is available on the Web site http://www.rxabbott.com or

in the United States by calling Abbott Medical Information at

1-800-633-9110.

About Abbott

Abbott is a global, broad-based health care company devoted to the

discovery, development, manufacture and marketing of pharmaceuticals

and medical products, including nutritionals, devices and

diagnostics. The company employs 65,000 people and markets its

products in more than 130 countries.

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