Healthcare Industry News: Methotrexate
News Release - October 23, 2006
New Phase III Data Shows Abbott's HUMIRA(R) (Adalimumab) Induced Clinical Remission In Patients With Crohn's Disease Who Lost Response to, or Were Intolerant to, Remicade(R) (Infliximab)Study Demonstrates Promising Results in Tough-to-Treat Crohn's Disease Patients
ABBOTT PARK, Ill., Oct. 23 (HSMN NewsFeed) -- Abbott today announced results from a study showing HUMIRA® (adalimumab) induced significantly higher rates of clinical remission compared to placebo in patients with moderately to severely active Crohn's disease who lost response to, or were intolerant to, infliximab therapy. The data is being presented simultaneously at the American College of Gastroenterology (ACG) annual meeting in Las Vegas and the United European Gastroenterology Week (UEGW) in Berlin.
Crohn's disease is a serious, chronic inflammatory disease of the gastrointestinal (GI) tract that may affect more than one million people in North America and Europe. There is no medical or surgical cure for Crohn's disease and few options for patients suffering with this chronic condition.
Data from GAIN, Gauging Adalimumab effectiveness in Infliximab Non- Responders, showed three times the percentage of patients with moderately to severely active Crohn's disease (CDAI 220-450) who had lost response to, or were intolerant to, infliximab achieved clinical remission with HUMIRA versus placebo at week four. Clinical remission was measured by a decrease in the Crohn's Disease Activity Index (CDAI) to less than 150 points.
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.
HUMIRA met the primary endpoint in GAIN, which was the proportion of patients achieving clinical remission (CDAI < 150) at week four compared to placebo. Significantly higher rates of clinical remission were observed for patients receiving HUMIRA compared to those receiving placebo at week four, 21 percent versus seven percent respectively (p less than or equal to 0.001).
"The results of the GAIN study suggest the potential of HUMIRA to help patients who lost response or were intolerant to infliximab therapy and positively impact both their disease and quality of life," said Stephen Hanauer, M.D., professor of medicine and clinical pharmacology chief, Section of Gastroenterology and Nutrition, University of Chicago. "These data are encouraging for patients and physicians dealing with this debilitating disease."
The GAIN Study
GAIN, a randomized, double-blind, placebo-controlled study of 325 patients who lost previous response to, or were intolerant to, infliximab, was designed to assess the efficacy and safety of HUMIRA versus placebo for induction of clinical remission in moderately to severely active Crohn's disease (CDAI 220- 450), measured at four weeks. Of the 325 patients included in the trial, 159 received initiating treatment with HUMIRA, 160 mg at week zero followed by 80 mg at week two, and the remaining 166 patients received placebo.
Results were also significant in the study's secondary endpoints, clinical response 70 (CR-70) defined as a decrease from baseline CDAI of greater than or equal to 70 points, and clinical response 100 (CR-100), defined as a decrease from baseline CDAI of greater than or equal to 100 points. More than half (52 percent) of patients receiving HUMIRA achieved CR-70 at week four, compared to one in three (34 percent) receiving placebo (p less than or equal to 0.001). At week four, 38 percent of patients taking HUMIRA, versus 25 percent of patients receiving placebo, achieved CR-100 (p less than or equal to 0.01). In addition, 52 percent of patients receiving HUMIRA achieved CR-70 at week two, compared to 33 percent of patients receiving placebo (p less than or equal to 0.01).
The safety profile in the GAIN study was consistent with previous reports in Crohn's disease and rheumatoid arthritis studies of HUMIRA. The most frequently reported treatment emergent adverse events (greater than or equal to 5 percent) for patients in the HUMIRA arm included abdominal pain, joint pain, headache, and injection site irritation.
"The findings of the GAIN study are significant, because they provide data showing that HUMIRA induced clinical remission and response in this difficult to treat Crohn's disease patient population," said Eugene Sun, M.D., vice president, Global Pharmaceutical Clinical Development, Abbott.
About Crohn's Disease
Crohn's disease 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. 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 will require a second surgery.
HUMIRA Regulatory Filings in Crohn's Disease
In September 2006, Abbott announced it had simultaneously submitted a supplemental Biologics License Application (sBLA) with the FDA and a Type II Variation to the European Medicines Agency (EMEA) seeking approval to market HUMIRA as a treatment for moderately to severely active Crohn's disease. 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. Crohn's disease is the fourth of seven diseases Abbott is studying for HUMIRA therapy.
Important Safety Information
Serious infections, sepsis, tuberculosis (TB) and rare cases of opportunistic infections, including fatalities, have been reported with the use of TNF-blocking agents, including HUMIRA. Many of these serious infections have 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.
In HUMIRA clinical trials for ankylosing spondylitis and psoriatic arthritis, the safety profile for patients treated with HUMIRA was similar to the safety profile seen in patients with rheumatoid arthritis.
HUMIRA is the only fully human monoclonal antibody approved for the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) in the U.S. and Europe. HUMIRA resembles antibodies normally found in the body. It works by blocking tumor necrosis factor alpha (TNF-a), a protein that plays a central role in the inflammatory responses of autoimmune diseases. 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 autoimmune diseases.
In the U.S., HUMIRA is 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 is also indicated for reducing the signs and symptoms of active arthritis in patients with PsA. HUMIRA can be used alone or in combination with Methotrexate or other disease-modifying anti-rheumatic drugs (DMARDs). HUMIRA was also approved on July 28, 2006 for reducing signs and symptoms in patients with active AS.
In Europe, HUMIRA, in combination with Methotrexate, is indicated for the treatment of moderate to severe, active RA in adult patients when the response to DMARDs including Methotrexate (MTX) has been inadequate. HUMIRA is also indicated for the treatment of severe, active and progressive RA in adults not previously treated with MTX. Additionally, HUMIRA is indicated for the treatment of active and progressive PsA and severe, active AS in adults when the response to previous DMARD-therapy has been inadequate.
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.
More information about 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.
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.
Abbott's news releases and other information are available on the company's Web site at http://www.abbott.com.
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