Wednesday 15th March, 2006
Findings from two Phase 3 studies show high-level, sustained response with maintenance therapy.
Phase 3 data show treatment with REMICADE? (infliximab) resulted in rapid, significant improvement and long-term response in patients with moderate to severe plaque psoriasis.
Findings from the EXPRESS II trial, a placebo-controlled, dose-ranging study of REMICADE 3 mg/kg and 5 mg/kg, showed that every eight week maintenance therapy resulted in greater long-term skin clearance compared with "as-needed" therapy regimens within each dose. At week 10, after infusions at weeks 0, 2 and 6, 70 percent of patients treated with REMICADE 3 mg/kg and 75 percent of patients receiving 5 mg/kg achieved at least 75 percent improvement in psoriasis as measured by Psoriasis Area Severity Index (PASI 75), compared with two percent of patients receiving placebo (P < 0.001). At week 50, patients receiving REMICADE 5 mg/kg every eight-week maintenance therapy achieved the highest level of sustained PASI improvement with the majority of the patients achieving PASI 75 versus the REMICADE 3 mg/kg eight-week maintenance therapy and the REMICADE 3 mg/kg and 5 mg/kg "as-needed" therapy regimens. Results from EXPRESS II and the previous Phase 3 EXPRESS study were presented today at the 64th annual American Academy of Dermatology meeting.
"We now have data showing that the majority of patients receiving scheduled REMICADE maintenance therapy achieved long-term clinical response in psoriasis, a lifelong, chronic inflammatory disease" said Alan Menter, MD, chairman, Division of Dermatology, Baylor University Medical Center, and lead study investigator. "These findings support previous clinical results and show that patients treated with REMICADE achieved rapid and marked improvement in the moderate to severe category of psoriasis, which impacts the lives of nearly two million Americans."
Consistency of response of REMICADE 5 mg/kg maintenance
therapy: Data from EXPRESS and EXPRESS II
In order to evaluate the consistency of response across both Phase 3 studies, data was analyzed from the REMICADE 5 mg/kg every eight week maintenance arm of each trial, the only regimen common to both EXPRESS and EXPRESS II. At week 10, after infusions at weeks 0, 2, and 6, the proportions of patients achieving PASI 75 were 80 percent versus three percent of placebo patients for EXPRESS and 75 percent versus two percent of placebo patients for EXPRESS II, (both P < 0.001 versus placebo). At week 10, the proportions of patients achieving PASI 90, or nearly complete skin clearance, were 57 percent versus one percent of placebo patients for EXPRESS and 45 percent versus 0.5 percent of placebo patients for EXPRESS II, (both P < 0.001 versus placebo). PASI 75 responses achieved at week 10 were maintained through week 26 in both EXPRESS and EXPRESS II (81 percent and 78 percent of patients achieved at least PASI 75 improvement from baseline, respectively), and the majority of patients achieved PASI 75 at week 50 in the REMICADE 5 mg/kg every eight-week maintenance groups.
"These data show great potential for REMICADE in the treatment of a disease that often carries great physical and emotional challenges," said Robert Matheson, MD, Oregon Medical Research Center, and study investigator. "The potential of achieving nearly complete skin clearance is exciting and holds great promise for patients with this difficult to treat disease."
Investigators reported that at week 10 patients in both EXPRESS and EXPRESS II receiving REMICADE experienced improvements in the Dermatology Life Quality Index (DLQI) and Physician's Global Assessment (PGA), measures of quality of life and psoriasis severity, respectively. In both studies, following 5 mg/kg induction therapy, REMICADE-treated patients experienced a median improvement of nine points in DLQI, a change that is considered to be a clinically meaningful decrease in psoriasis-related burden for the patient, compared to no improvement for placebo patients (REMICADE vs. placebo, -9.0 versus 0.0, P < 0.001 for both studies). The proportions of patients with a PGA of cleared, excellent/minimal were 83 percent vs. 4 percent (EXPRESS) and 76 percent vs. 1 percent (EXPRESS II) for the REMICADE and placebo groups respectively (both P < 0.001 vs. placebo). The PGA scale indicates a physician's assessment of the severity of psoriasis and scores of cleared, excellent/minimal are consistent with complete or almost complete clearing of the disease.
In November 2005, Centocor, Inc. announced that the United States Food and Drug Administration (FDA) accepted its filing of a supplemental Biologics License Application (sBLA) for the use of REMICADE in the treatment of moderate to severe plaque psoriasis. The acceptance of the sBLA file for psoriasis follows the September 2005 European Commission approval of REMICADE for the treatment of moderate to severe plaque psoriasis in adults who failed to respond to, or have a contraindication to, or are intolerant of other systemic therapy including cyclosporine, methotrexate or psoralen plus ultraviolet light A (PUVA). REMICADE is approved in the U.S. and the European Union (EU) for the treatment of active psoriatic arthritis.
The European Infliximab for Psoriasis [REMICADE] Efficacy and Safety Study (EXPRESS) was a Phase 3, multi-center, randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of REMICADE induction and maintenance therapy in 378 patients with moderate to severe plaque psoriasis who were candidates for phototherapy or systemic therapy. Patients received either REMICADE 5 mg/kg or placebo administered at weeks 0, 2 and 6, followed by maintenance treatment every 8 weeks. The REMICADE group continued on maintenance treatments every 8 weeks. Beginning at week 24, patients randomized to the placebo group were crossed over to receive REMICADE 5 mg/kg at weeks 24, 26 and 30, and every 8 weeks through week 46.
Through week 24 of the EXPRESS trial, adverse events (AEs) occurred at a higher incidence in the REMICADE group (82 percent) compared with the placebo group (71 percent). Laboratory abnormalities were uncommon, with an elevation in liver function tests being the most common abnormality. Through week 24, markedly abnormal alanine aminotransferase (ALT) values (predefined as greater than 150 IU/L and greater than or equal to 100 percent increase from baseline) occurred in 6 percent of subjects in the REMICADE group compared with no subjects in the placebo group. There were more serious AEs (6 percent), including one fatal infection, in the REMICADE group than in the placebo group (3 percent). AEs observed were generally consistent with those described in the prescribing information, including information regarding serious infections. Please see "Important Safety Information" below.
About EXPRESS II
The Evaluation of Infliximab for Psoriasis [REMICADE] Efficacy and Safety Study (EXPRESS II) was a Phase 3, multi-center, randomized, double-blind, placebo-controlled trial examining the safety and efficacy of REMICADE in 835 patients with moderate to severe plaque psoriasis who were candidates for phototherapy or systemic therapy. Patients were randomized to induction doses of REMICADE 3 mg/kg or 5 mg/kg or placebo at weeks 0, 2 and 6. Patients in the active induction treatment groups were randomized again at week 14 to receive either scheduled or "as-needed" maintenance treatment at the same dose administered during the induction phase. Patients in the placebo group were crossed over at week 16 to receive REMICADE 5 mg/kg at weeks 16, 18 and 22, and every 8 weeks through week 46.
In EXPRESS II, through week 14 (the placebo-controlled period), AEs occurred at a higher incidence in the REMICADE groups (63 percent and 69 percent in the 3 mg/kg and 5 mg/kg, respectively) compared with the placebo group (56 percent). Serious AEs occurred at rates of 2 percent in the placebo group, 3 percent in the 5 mg/kg group and 1 percent in the 3 mg/kg group. Laboratory abnormalities were uncommon, with an elevation in liver function tests being the most common abnormality. Through week 50, markedly abnormal alanine aminotransferase (ALT) values (predefined as greater than 150 IU/L and greater than or equal to 100 percent increase from baseline) occurred in 5 percent of REMICADE-treated subjects in EXPRESS II. Through week 50, there were two cases of tuberculosis in the REMICADE treatment groups. AEs observed were generally consistent with those described in the prescribing information, including information regarding serious infections. Please see "Important Safety Information" below.
Psoriasis is a chronic, immune-mediated disease, which results when skin cells over-produce and accumulate on the surface causing red, scaly plaques that may itch and bleed. This chronic inflammation is driven in part by tumor necrosis factor alpha, or TNF-alpha, a cytokine involved in the body's normal immune response. TNF-alpha is found at increased levels in psoriatic plaques and plays a crucial part in their formation and continued existence. It is estimated that two percent of the U.S. population has psoriasis, and about 30 percent of people with psoriasis have cases that are considered moderate to severe.
REMICADE is the global market leader among anti-tumor necrosis factor alpha (TNF-alpha) therapies and has demonstrated broad clinical utility in rheumatoid arthritis (RA), Crohn's disease (CD), psoriatic arthritis (PsA), ulcerative colitis (UC), and ankylosing spondylitis (AS). The safety and efficacy of REMICADE have been well established in clinical trials over the past 13 years and through commercial experience with over 700,000 patients treated worldwide.
In the U.S., REMICADE, in combination with methotrexate, is indicated for reducing signs and symptoms, inhibiting the progression of structural damage and improving physical function in patients with moderately to severely active RA. REMICADE is the only biologic indicated for the treatment of patients with moderately-to-severely active CD who have had an inadequate response to conventional therapy. REMICADE is also indicated for reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in patients with fistulizing CD. In December 2004, REMICADE was approved for reducing signs and symptoms in patients with active AS. In May 2005, REMICADE was approved for reducing signs and symptoms of active arthritis in patients with PsA. Additionally, in September 2005, REMICADE was approved for reducing signs and symptoms, achieving clinical remission and mucosal healing, and eliminating corticosteroid use in patients with moderately to severely active UC who have had an inadequate response to conventional therapy. This approval makes REMICADE the first and only biologic approved for the treatment of moderate to severe UC.
REMICADE is unique among available anti-TNF biologic therapies. Unlike self-administered therapies that require patients to inject themselves frequently, REMICADE is the only anti-TNF biologic administered directly by caregivers in the clinic or office setting. In RA (3 mg/kg), CD (5 mg/kg), PsA (5 mg/kg), and UC (5 mg/kg), REMICADE is a two-hour infusion administered every 8 weeks, following a standard induction regimen that requires treatment at weeks 0, 2 and 6. As a result, REMICADE patients may require as few as six treatments each year. In AS (5 mg/kg), REMICADE is a two-hour infusion administered every 6 weeks, following a standard induction regimen that requires treatment at weeks 0, 2 and 6.
Important Safety Information
There are reports of serious infections, including tuberculosis (TB), sepsis and pneumonia. Some of these infections have been fatal. Tell your doctor if you have had recent or past exposure to people with TB. Your doctor will evaluate you for TB and perform a skin test. If you have latent (inactive) TB, your doctor should begin TB treatment before you start REMICADE. REMICADE can lower your ability to fight infections, so if you are prone to or have a history of infections, or develop any signs of an infection such as fever, fatigue, cough, or the flu while taking REMICADE, tell your doctor right away. Also tell your doctor if you have lived in a region where histoplasmosis or coccidioidomycosis is common.
Many people with heart failure should not take REMICADE; so prior to treatment you should discuss any heart condition with your doctor. Tell your doctor right away if you develop new or worsening symptoms of heart failure (such as shortness of breath or swelling of your ankles or feet).
There have been rare cases of serious liver injury in people taking REMICADE, some fatal. Contact your doctor immediately if you develop symptoms such as jaundice (yellow skin and eyes), dark brown urine, right-sided abdominal pain, fever, or severe fatigue.
Blood disorders have been reported, some fatal. Tell your doctor if you develop possible signs of blood disorders such as persistent fever, bruising, bleeding, or paleness while taking REMICADE. Nervous system disorders have also been reported. Tell your doctor if you have or have had a disease that affects the nervous system, or if you experience any numbness, weakness, tingling, or visual disturbances while taking REMICADE.
Reports of a type of blood cancer called lymphoma in patients on REMICADE or other TNF blockers are rare but occur more often than expected for people in general. People who have been treated for rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, or psoriatic arthritis for a long time, particularly those with highly active disease may be more prone to develop lymphoma. Cancers, other than lymphoma, have also been reported. If you take REMICADE or other TNF blockers, your risk for developing lymphoma or other cancers may increase. You should also tell your doctor if you have had or develop lymphoma or other cancers while you are taking REMICADE.
Serious infusion reactions have been reported with REMICADE, including hives, difficulty breathing, and low blood pressure. Reactions have occurred during or after infusions. In clinical studies, some people experienced the following common side effects: respiratory infections (that may include sinus infections and sore throat), coughing, and stomach pain or mild reactions to infusion such as rash or itchy skin.
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