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Biopharmaceuticals Gastroenterology

 News Release - October 21, 2008

Abbott's HUMIRA(R) (adalimumab) Data Shows Fistula Healing for Up to Three Years in Patients with Moderate to Severe Crohn's Disease

Additional Data Presented at United European Gastroenterology Week Show

Fistula Healing in Difficult-to-Treat Patients


VIENNA, Austria, October 21 -- (Healthcare Sales & Marketing Network) -- New data showed that Abbott's HUMIRA® (adalimumab) provided long-term treatment of fistulas, with more than half of patients with moderate to severe Crohn's disease experiencing fistula healing at three years, according to clinical research presented today at the United European Gastroenterology Week (UEGW) congress in Vienna. Data also showed response to HUMIRA in difficult-to-treat patients -- those with fistulas who had failed to respond, lost response to, or were intolerant of infliximab.

Fistulas are tunnels that form between the intestine and other parts of the body. They develop in up to one-third of people with Crohn's disease and are considered one of the most disabling complications of the disease. In these studies, fistula healing was defined as the absence of drainage from all fistulas, either spontaneously or with gentle compression.

"Fistulas can affect a patient's lifestyle due to discharge, bleeding and fecal incontinence, and can also lead to invasive surgery," said Jean-Frederic Colombel, M.D., professor, Gastroenterology, Hopital Huriez, Lille, France. "Treatments that promote fistula healing are important -- particularly for difficult-to-treat patients."

Study Results

Results from an open-label extension of the CHARM study, Abbott's one-year, Phase III trial, showed the effect of HUMIRA on fistula healing for up to three years.

-- More than half of patients (58 percent, 29/50) who had fistulas at baseline experienced fistula healing at the one-year completion of CHARM, and this was maintained through year one of the open-label extension. After a total of two years of treatment, the majority (59 percent, or 22/37) experienced fistula healing.

-- About two-thirds of patients (68 percent, 21/31 patients) who continued treatment through year two of the open-label extension (three total treatment years) experienced fistula healing.

A sub-analysis of the CHOICE trial, Abbott's open-label, single-arm study, assessed HUMIRA in treating patients with moderate to severe Crohn's disease who had failed infliximab. A total of 83 of the 88 patients with fistulas at baseline had data available at their last physician visit. Last visits ranged from week four to week 36.

-- Results showed that 41 percent of HUMIRA patients (34/83) had fistula healing at their last physician visit.

-- 42 percent of the 71 initial responders -- those who had developed intolerance or lost response to infliximab -- had complete fistula healing.

-- Four of the 12 patients who were infliximab primary non-responders experienced complete fistula healing.

"These data presented at UEGW represent the first time we have analyzed results of studies on fistula healing in HUMIRA patients who were primary non-responders to infliximab," said Rebecca Hoffman, M.D., divisional vice president, Global Pharmaceutical Research and Development, Abbott. "We are encouraged by these results and will continue to study HUMIRA in patients with Crohn's disease."

About CHARM

CHARM (Crohn's Trial of the Fully Human Antibody Adalimumab for Remission Maintenance) was a 56-week trial that enrolled 854 patients with moderate to severe Crohn's disease and evaluated HUMIRA for the maintenance of clinical remission. Following a four-week, open-label induction period, the 778 patients still participating in the trial were randomized to either HUMIRA (40 mg every other week or weekly), or placebo. The co-primary endpoints evaluated the maintenance of clinical remission at weeks 26 and 56 for the HUMIRA 40 mg every other week and 40 mg every week groups compared to those on placebo. A significantly greater percentage of patients treated with HUMIRA maintained clinical remission at one year compared to placebo.

The observed data included patients from CHARM who were followed for an additional two years in an ongoing open-label extension. The data analyzed both HUMIRA doses and evaluated the subgroup of patients from CHARM who had fistulas at baseline and enrolled into the open-label extension for further evaluation.

The analysis reported the percentage of patients with healed fistulas and percentage with greater than or equal to 50 percent fistula response up to three years.

About CHOICE

CHOICE (Crohn's Disease WHO Failed Prior Infliximab To Collect Safety Data and Efficacy Via Patient-reported Outcome Measures) is a multicenter, open-label, single-arm study that assessed HUMIRA in treating patients with moderate to severe Crohn's disease who had failed infliximab therapy. A sub-analysis of observed data evaluated fistula healing. The study included patients who had never responded to infliximab (primary non-responders) as well as patients who had previously responded but developed intolerance to or lost response to infliximab (initial responders). A total of 673 patients were enrolled, and 88 patients had fistulas at baseline. Of the patients with fistulas, 13 patients were primary nonresponders and 75 were initial responders.

After a minimum eight-week period to allow for infliximab to clear their systems, patients received 160 mg HUMIRA at week zero, 80 mg at week two, and 40 mg every other week through the end of the study. At or after eight weeks of HUMIRA treatment, non-responders or patients who had flares could be switched to 40 mg every week. The study time varied, with patients leaving the study when HUMIRA became commercially available for Crohn's disease in the United States.

About Crohn's Disease

Crohn's disease is a chronic autoimmune disease characterized by inflammation in the gastrointestinal tract. It affects people of all ages but it is primarily a disease of young adults, with onset typically before age 40. Common symptoms of the disease include diarrhea, cramping, abdominal pain, weight loss and fever. Complications include intestinal obstruction, fistulas (ulcers that form tunnels to surrounding tissues), and malnutrition. Over the course of their disease, at least 75 percent of patients with Crohn's will undergo surgery at least once for complications or disease resistant to treatment. Of those who undergo surgery to remove a portion of their intestines (resection), half will experience a relapse within five years.

Important Safety Information

Globally, prescribing information varies; refer to the individual country product label for complete information.

Serious infections, sepsis, rare cases of tuberculosis (TB), and opportunistic infections, including fatalities, have been reported with the use of TNF antagonists, including HUMIRA. Many of the serious infections have occurred in patients on concomitant immunosuppressive therapy that, in addition to their underlying disease could predispose them to infections. Patients must be monitored closely for infections, including tuberculosis, before, during and after treatment with HUMIRA. Treatment should not be initiated in patients with active infections until infections are controlled. HUMIRA should not be used by patients with active TB or other severe infections such as sepsis and opportunistic infections. If latent tuberculosis is diagnosed, appropriate treatment for latent tuberculosis must be initiated with anti-tuberculosis prophylaxis therapy before starting treatment with HUMIRA, and in accordance with local recommendations. Patients who develop new infections while using HUMIRA should be monitored closely. HUMIRA should be discontinued if a patient develops a new serious infection until infections are controlled. Physicians should exercise caution when considering use of HUMIRA in patients with a history of recurring infection or with underlying conditions that may predispose patients to infections.

TNF-blocking agents have been associated with reactivation of hepatitis B (HBV) in patients who are chronic carriers of the virus. Some cases have been fatal. Patients at risk for HBV infection should be evaluated for prior evidence of HBV infection before initiating HUMIRA.

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

TNF antagonists, including HUMIRA, have been associated in rare cases with demyelinating disease including multiple sclerosis, Guillain-Barre syndrome and optic neuritis, and serious allergic reactions. Rare reports of pancytopenia including aplastic anemia have been reported with TNF-blocking agents. Adverse events of the haematologic system, including medically significant cytopenia have been infrequently reported with HUMIRA.

More cases of malignancies including lymphoma have been observed among patients receiving a TNF-antagonist compared with control patients in clinical trials. The size of the control group and limited duration of the controlled portions of studies precludes the ability to draw firm conclusions. Furthermore, there is an increased background lymphoma risk in rheumatoid arthritis patients with long-standing, highly active, inflammatory disease, which complicates the risk estimation. During the long-term open-label trials with HUMIRA, the overall rate of malignancies was similar to what would be expected for an age, gender and race matched general population. With the current knowledge, a possible risk for the development of lymphomas or other malignancies in patients treated with a TNF antagonist cannot be excluded. All patients, and in particular patients with a medical history of extensive immunosuppressant therapy or psoriasis patients with a history of PUVA treatment, should be examined for the presence of non-melanoma skin cancer prior to and during treatment with HUMIRA.

Rare postmarketing cases of hepatosplenic T-cell lymphoma have been identified in patients treated with adalimumab. This rare type of T-cell lymphoma has a very aggressive disease course and is usually fatal. Some of these hepatosplenic T-cell lymphomas with HUMIRA have occurred in young adult patients on concomitant treatment with azathioprine or 6-mercaptopurine used for Crohn's disease. A risk for the development of hepatosplenic T-cell lymphoma in patients treated with HUMIRA cannot be excluded.

In clinical studies with another TNF antagonist, a higher rate of serious congestive heart failure (CHF) related adverse events including worsening CHF and new onset CHF have been reported. Cases of worsening CHF have also been reported in patients receiving HUMIRA. Physicians should exercise caution when using HUMIRA in patients who have heart failure and monitor them carefully. HUMIRA should not be used in patients with moderate or severe heart failure.

The most frequently reported adverse event (>/= 1/10 patients) at least possibly causally related to HUMIRA is injection site reaction (including pain, swelling, redness or pruritus). Other common adverse events (reported by >/= 1/100 patients) at least possibly causally related to HUMIRA include lower respiratory infections (including pneumonia, bronchitis), viral infections (including influenza, herpes infections), candidiasis, bacterial infection (including urinary tract infections), upper respiratory infection, dizziness (including vertigo), headache, neurologic sensation disorders (including paraesthesias), Cough, nasopharyngeal pain, diarrhea, abdominal pain, stomatitis and mouth ulceration, nausea, hepatic enzymes increased, rash, pruritus, musculoskeletal pain, pyrexia, fatigue (including asthenia and malaise). Adverse drug reactions reported post-marketing include intestinal perforation, interstitial lung disease including pulmonary fibrosis and cutaneous vasculitis.

About HUMIRA

HUMIRA is the only fully human monoclonal antibody approved for the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), psoriasis, ankylosing spondylitis (AS), Crohn's disease and juvenile idiopathic arthritis (JIA) in the United States and Europe. HUMIRA resembles antibodies normally found in the body. It works by blocking tumor necrosis factor alpha (TNF-alpha), a protein that, when produced in excess, plays a central role in the inflammatory responses of many immune-mediated diseases. To date, HUMIRA has been approved in 77 countries and more than 310,000 people worldwide are currently being treated with HUMIRA. Clinical trials are also under way evaluating the potential of HUMIRA in ulcerative colitis.

In Europe, HUMIRA, in combination with methotrexate (MTX), is indicated for the treatment of moderate to severe, active RA in adult patients when the response to disease-modifying anti-rheumatic drugs (DMARDs) including MTX has been inadequate, and 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 with 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.

Also in Europe, HUMIRA is indicated for the treatment of active and progressive PsA in adults when the response to previous DMARD therapy has been inadequate. HUMIRA has been shown to reduce the rate of progression of peripheral joint damage as measured by x-ray in patients with polyarticular symmetrical subtypes of the disease and to improve physical function.

HUMIRA is indicated for the treatment of severe, active AS in adults who have had an inadequate response to conventional therapy.

HUMIRA is indicated for treatment of severe, active Crohn's disease, in patients who have not responded despite a full and adequate course of therapy with a corticosteroid and/or an immunosuppressant; or who are intolerant to or have medical contraindications for such therapies. For induction treatment, HUMIRA should be given in combination with cortiocosteroids. HUMIRA can be given as monotherapy in case of intolerance to corticosteroids or when continued treatment with corticosteroids is inappropriate.

HUMIRA is indicated for the treatment of moderate to severe chronic plaque psoriasis in adult patients who failed to respond to or who have a contraindication to, or are intolerant to other systemic therapy including cyclosporine, methotrexate or PUVA. HUMIRA in combination with methotrexate is indicated for the treatment of active polyarticular juvenile idiopathic arthritis, in adolescents aged 13 to 17 years who have had an inadequate response to one or more DMARDs. HUMIRA can be given as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate.

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, Mass., United States, is a world-class discovery and basic research facility committed to finding new treatments for autoimmune diseases.

About Abbott

Abbott (NYSE: ABT ) 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 more than 68,000 people and markets its products in more than 130 countries.

Abbott's news releases and other information are available on the company's Web site at http://www.abbott.com.

Web site: http://www.abbott.com


Source: Abbott

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