Healthcare Industry News: Methotrexate
News Release - May 22, 2006
Promising Pivotal Phase III Data Show Abbott's Humira(R) (Adalimumab) Maintained Clinical Remission in Patients With Crohn's Disease Through One YearAdditional Data From CHARM Study Evaluated Discontinuation of Steroid Use and Fistula Closure
ABBOTT PARK, Ill., May 22 (HSMN NewsFeed) -- Abbott (NYSE: ABT ) today announced results from a study showing patients with moderate to severely active Crohn's disease treated with HUMIRA® (adalimumab) were more likely to maintain clinical remission through one year than patients receiving a placebo, regardless of the frequency of the dosing regimen. The data, presented at the Digestive Disease Week (DDW) annual meeting in Los Angeles, will support Abbott's anticipated regulatory filing for an indication for Crohn's disease, a serious, chronic inflammatory disease of the gastrointestinal (GI) tract. Crohn's disease is the fourth of six autoimmune diseases targeted for HUMIRA therapy.
Data from CHARM, the Crohn's trial of the fully Human antibody Adalimumab for Remission Maintenance, showed that remission rates were maintained through 56 weeks in patients who demonstrated response to HUMIRA during a four-week open-label induction phase. Clinical remission was measured by a decrease in the Crohn's Disease Activity Index (CDAI). 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.
Co-primary endpoints in CHARM were clinical remission rates at week 26 and week 56. The data showed significantly higher remission rates (CDAI<150) at weeks 26 and 56 versus placebo, among patients with a decrease in CDAI greater than or equal to 70 points at week four. In addition, the percent of patients in clinical remission on the two dosing regimens was comparable. Of the 172 patients treated with HUMIRA every other week, 40 percent were in clinical remission at week 26 (p<0.001) and more than one-third (36 percent) were in remission at week 56 (p<0.001). Of the 157 patients taking HUMIRA weekly, nearly half (46 percent) achieved clinical remission from Crohn's disease at week 26 (p<0.001) and 41 percent maintained remission at week 56 (p<0.001). In comparison, of the 170 patients receiving placebo, 17 percent achieved clinical remission at week 26 and 12 percent maintained remission at week 56.
"Hundreds of thousands of people, many of whom are young and active adults, suffer from this chronic condition and, to this point, have had limited effective, long-term treatment options," said trial investigator William J. Sandborn, M.D., Inflammatory Bowel Disease Clinic, Division of Gastroenterology and Hepatology, Mayo Clinic and Mayo Medical School, Rochester, Minn. "The findings from CHARM add to the growing body of scientific evidence supporting adalimumab (HUMIRA) as a potential treatment for moderate to severely active Crohn's disease."
The CHARM Trial
CHARM is a Phase III double-blind, placebo-controlled, multi-center, 56- week trial. It was designed to assess the efficacy and safety of HUMIRA (adalimumab) taken weekly and every other week, versus placebo, in maintaining clinical remission (CDAI<150) at week 26 and week 56 in patients with moderate to severely active Crohn's disease (CDAI 220-450) who responded to open-label induction therapy.
Co-primary endpoints in CHARM were clinical remission rates at week 26 and week 56. Major secondary endpoints in CHARM included measurement of clinical response (CDAI decrease by at least 70 and 100 points), discontinuation of steroids while in remission, fistula counts, and scores from the Inflammatory Bowel Disease Questionnaire (IBDQ) and the SF-36, both of which measure health status and quality of life.
The trial included 854 patients who received open-label induction therapy with HUMIRA 80 mg at week zero and 40 mg at week two. Seventy-six patients withdrew prior to randomization. All of the remaining 778 patients at week four were randomized to receive HUMIRA 40 mg every other week, HUMIRA 40 mg weekly or placebo through week 56. The 499 patients (58 percent) with week four clinical response to HUMIRA (a CDAI decrease equal to or greater than 70 from baseline) made up the primary efficacy analysis group.
At week eight, steroid tapering was permitted for those responding to treatment. All patients with active fistulas at both screening and baseline visits, regardless of their response to HUMIRA during the open-label induction period, were assessed for fistula closure.
Additional CHARM Results
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 26, 35 percent of patients receiving HUMIRA every other week and 30 percent of patients taking HUMIRA weekly discontinued the use of steroids and remained in remission, compared to 3 percent of patients receiving placebo (p less than or equal to 0.001). At week 56, 29 percent of patients taking HUMIRA every other week and 23 percent of patients taking HUMIRA weekly discontinued the use of steroids and maintained remission, compared to 6 percent of those receiving placebo (p less than or equal to 0.008). Steroids can produce severe adverse effects and are not recommended for long-term treatment.
In CHARM, the ability of HUMIRA to treat draining cutaneous fistulas, the abnormal connections that form between the intestine and the skin in patients with Crohn's disease, was also assessed. Among all patients with draining cutaneous fistulas at both screening and baseline, regardless of response to HUMIRA at week four, one-third of patients (33 percent) achieved complete closure of fistulas when receiving HUMIRA either every other week or weekly (n=70, p<0.016) compared with 13 percent of patients receiving placebo (n=47). Complete fistula closure was defined as no draining fistulas for at least the last two post-baseline evaluations.
"Results from CHARM reaffirm the potential of HUMIRA to provide long-term management of this often difficult to treat disease," said Eugene Sun, M.D., vice president, Global Pharmaceutical Clinical Development at Abbott. "Since its initial approval, more than 150,000 patients worldwide have been treated with HUMIRA. Abbott remains committed to exploring the full therapeutic potential of HUMIRA in a variety of autoimmune diseases."
The safety profile in the CHARM study was consistent with previous reports of studies of adalimumab.
About Crohn's Disease
Crohn's disease is a serious chronic and inflammatory disease of the gastrointestinal tract that may affect up to 600,000 North Americans and is typically diagnosed before age 40. Common symptoms of the disease include diarrhea, cramping, abdominal pain, weight loss, fever, and in some cases, rectal bleeding. Crohn's disease can have a devastating impact on the lifestyles of patients, many of whom are young and active. Currently, there is no cure for Crohn's disease, making suppression of inflammatory response the goal of treatment.
Abbott Initiates Crohn's Disease Treatment Protocol
Abbott has received FDA approval to initiate a Treatment Protocol to study the use of adalimumab in patients no longer responding to or 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 immediately life-threatening disease who are not involved in the clinical trials, and to obtain additional data on the drug's safety and effectiveness. Additional information about the Treatment Protocol is available through Abbott Medical Information, 1-800-633- 9110, and on the Abbott Web site, http://www.abbott.com .
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. 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.
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 rheumatoid arthritis. HUMIRA can be used alone or in combination with Methotrexate (MTX) or other DMARDS (disease-modifying anti-rheumatic drugs).
HUMIRA is 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.
Clinical trials are currently underway evaluating the potential of HUMIRA in other autoimmune 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, Mass., 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 sites http://www.abbottimmunology.com and http://www.HUMIRA.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 100 countries.
Abbott's news releases and other information are available on the company's Website at http://www.abbott.com .
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