Abbott's Humira (Adalimumab) Receives Positive Opinion from European Medicines Agency for the Treatment of Crohn's Disease
ABBOTT PARK, Ill., April 27, 2007 /PRNewswire-FirstCall/ -- Abbott announced today that the Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the European Medicines Agency (EMEA), granted a positive opinion recommending approval of HUMIRA(R) (adalimumab) for the treatment of severe Crohn's disease. HUMIRA will be the first self-administered biologic for the treatment of Crohn's disease. This is an important milestone for Abbott, as Crohn's disease will be the fourth approved indication for HUMIRA.
Crohn's disease is a serious, chronic, inflammatory disease of the gastrointestinal (GI) tract that affects more than 1 million people in Europe and North America. There is no medical or surgical cure for Crohn's disease and there are few treatment options for patients suffering with this chronic condition. Crohn's affects people of all ages but it is primarily a disease of adolescents and young adults, with onset typically between the ages of 15 and 40.
"HUMIRA will fill an important unmet need in Crohn's, a condition where we've had few effective treatment options, by offering sustained remission from disease and improved quality of life," said Jean-Frederic Colombel, M.D., professor of Gastroenterology, Hopital Huriez, France. "HUMIRA has been shown to be effective even in patients who have failed other therapies."
The European Commission is expected to issue a decision granting the marketing authorization for HUMIRA as a treatment of Crohn's disease in the European Union within the next 60 days. In Feb. 2007, HUMIRA was approved under priority review by the U.S. Food and Drug Administration for the treatment of moderately to severely active Crohn's disease.
"The expected European approval of HUMIRA for the treatment of Crohn's disease represents a much anticipated option for physicians and patients," said Eugene Sun, M.D., vice president, Global Pharmaceutical Clinical Development at Abbott. "HUMIRA offers patients sustained response and convenience as the only self-injectable biologic therapy."
The positive opinion is based on results of three randomized, double-blind, placebo-controlled, multi-center trials of HUMIRA. Clinical remission was measured by 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, levels of general well being and other measures.
-- CLASSIC I (Clinical assessment of Adalimumab Safety and efficacy Studied as an Induction therapy in Crohn's disease) was a study of 299 patients with moderate to severe Crohn's disease who were new to anti-TNF (tumor necrosis factor) therapy. Results showed that treatment with HUMIRA resulted in a greater percentage of patients achieving clinical remission at four weeks compared to placebo. -- 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 severely active Crohn's disease. The 499 patients who demonstrated clinical response (CDAI decrease of greater than or equal to 70 points from baseline) to HUMIRA during a four-week, open-label induction phase were randomized to receive either HUMIRA or placebo. A greater percentage of those who continued on HUMIRA maintained clinical remission through one year compared to placebo. -- GAIN (Gauging Adalimumab effectiveness in Infliximab Non-Responders) evaluated the efficacy of HUMIRA in 325 patients with moderate to severely active Crohn's disease who had previously lost response or were unable to tolerate infliximab. HUMIRA induced significantly higher rates of clinical remission compared to placebo.
The safety profile of HUMIRA in the Crohn's clinical trials was similar to that seen in HUMIRA clinical trials for rheumatoid arthritis (RA). Adverse events reported by >5 percent of HUMIRA treated patients with a greater incidence than patients taking placebo include injection site irritation, injection site pain, injection site reaction, nausea, joint pain, inflammation of the nose and pharynx, abdominal pain, and headache.
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 chronic diarrhea, cramping, abdominal pain, weight loss, fever, and in some cases, rectal bleeding. 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 About HUMIRA
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 RA 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. 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 is not recommended.
TNF antagonists, including HUMIRA, have been associated in rare cases with demyelinating disease 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.
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.
Common adverse events (>1/100 and >1/10) 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, lymphopenia, dizziness (including vertigo), headache, neurologic sensation disorders (including paraesthesias), infection, irritation or inflammation of the eye, cough, nasopharyngeal pain, diarrhea, abdominal pain, stomatitis and mouth ulceration, nausea, hepatic enzymes increased, rash, dermatitis and eczema, pruritus, hair loss, musculoskeletal pain, pyrexia, fatigue (including asthenia and malaise). Injection site reaction (including pain, swelling, redness or pruritus) was reported by >1/10 patients.
HUMIRA is approved for the treatment of RA, psoriatic arthritis (PsA), and ankylosing spondylitis (AS) in Europe and the U.S. HUMIRA resembles antibodies normally found in the body. It works by blocking tumor necrosis factor alpha (TNF-.), 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 67 countries and more than 180,000 people worldwide are currently being treated with HUMIRA. Clinical trials are currently under way evaluating the potential of HUMIRA in other immune-mediated diseases.
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. Additionally, HUMIRA is indicated for the treatment of active and progressive PsA in adults when the response to previous DMARD-therapy has been inadequate and for the treatment of severe, active AS in adults who have had an inadequate response to conventional therapy.
Abbott is a global, broad-based health care company devoted to the discovery, development, manufacture and marketing of pharmaceuticals and medical products, including nutritionals and devices. The company employs 65,000 people and markets its products in more than 130 countries.
Posted: April 2007
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