FDA Accepts Application Requesting Approval of REMICADE(R) in the Treatment of Moderate to Severe Plaque Psoriasis 


Supporting Data from Two Phase 3 Studies Show Rapid and Significant Clearance of Skin Disease.

MALVERN, Pa., Nov. 7 /PRNewswire/ -- Centocor, Inc. announced today that the U.S. Food and Drug Administration (FDA) has accepted its filing of a supplemental Biologics License Application (sBLA) for the use of REMICADE (infliximab) in the treatment of moderate to severe plaque psoriasis. It is estimated that nearly two million Americans suffer from moderate to severe psoriasis, a chronic, immune-mediated inflammatory disease that can be both
physically and emotionally debilitating.(1)

 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). In May 2005 the FDA approved REMICADE for reducing signs and symptoms of active arthritis in patients with psoriatic arthritis. Acceptance of the sBLA filing does not mean that a license has been issued for this indication nor does it represent any evaluation of the adequacy of the data submitted in the sBLA. 

"The results we have seen in dermatologic clinical trials evaluating REMICADE have been very encouraging," said Cynthia Guzzo, M.D., Executive Director, Immunology,  Centocor, Inc. "The continued study of REMICADE for the treatment of psoriatic disease demonstrates the commitment of Centocor to the dermatology community and to advancing treatment expectations for physicians and patients." 

The sBLA filing is based on results of two phase 3, multi-center,
randomized, double-blind, placebo-controlled trials, European Infliximab for Psoriasis [REMICADE] Efficacy and Safety Study (EXPRESS) and Evaluation of Infliximab for Psoriasis in a [REMICADE] Efficacy and Safety Study (EXPRESS II).

About EXPRESS

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 therapy through week 46.

Results from EXPRESS showed that a majority of REMICADE-treated patients achieved clinically significant levels of skin clearance. At week 10, 80 percent of patients receiving REMICADE achieved at least 75 percent improvement frombaseline in psoriasis as measured by the Psoriasis Area and Severity Index (PASI 75), and 57 percent achieved PASI 90, near complete skin clearance, versus 3 percent and 1 percent of patients receiving placebo, respectively (P < 0.001).

Results were maintained at week 24 with 82 percent of REMICADE-treated patients achieving PASI 75, and 58 percent of patients achieving PASI 90 responses, versus 4 percent and 1 percent of patients receiving placebo, respectively (P < 0.001). The majority of patients maintained significant improvement in psoriasis through week 50 with continued REMICADE treatment.

In EXPRESS, through week 24, AEs occurred at a higher incidence in the REMICADE group (82 percent) compared with the placebo group (71 percent). The only clinically significant laboratory abnormalities that occurred more frequently in the REMICADE group compared with placebo were elevated liver enzyme tests. 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

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, then every 8 weeks through week 46.

EXPRESS II independently substantiated the EXPRESS study findings. In addition, the EXPRESS II study showed that scheduled maintenance treatment with REMICADE resulted in greater long-term control of skin clearance compared with "as-needed" therapy regimens. In the study, at week 10, 70 percent of patients receiving REMICADE 3 mg/kg and 75 percent of patients receiving
REMICADE 5 mg/kg achieved at least PASI 75, versus 2 percent of patients receiving placebo (P < 0.001). The majority of patients in the scheduled maintenance groups maintained significant improvement in psoriasis through week 50 with continued REMICADE treatment. PASI responses were also accompanied by significant improvements in health-related quality of life. 

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). The only clinically significant laboratory abnormalities that occurred more frequently in the REMICADE group compared with placebo were elevated liver enzyme tests. 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. AEs observed were generally consistent with those described in the prescribing information, including information regarding serious infections. Please see "Important Safety Information" below.

About Psoriasis

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.

About Psoriatic Arthritis

Psoriatic arthritis involves joint pain and swelling that can lead to
debilitation coupled with inflamed, scaly, red patches of psoriasis. Symptoms may include stiffness and tenderness of the joints and surrounding tissue, reduced range of motion, nail changes and redness and pain of the eye, or uveitis. Joints of the hands, wrists, knees, ankles, feet, lower back and neck are commonly affected. Approximately one million Americans have psoriatic arthritis, and the disease affects both men and women equally, most commonly between the ages 30 and 50.

About REMICADE

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 12 years and through commercial experience with over 600,000 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. On May 13, 2005, REMICADE was approved for reducing signs and symptoms of active arthritis in patients with PsA. Additionally, on September 15, 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, CD and PsA, 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, REMICADE is a two-hour infusion (5 mg/kg) administered every 6 weeks, following a standard induction regimen that requires treatment at weeks 0, 2, and 6. In UC, REMICADE is a two-hour infusion (5 mg/kg) administered every 8 weeks, following a standard induction regimen that requires treatment at weeks 0, 2, and 6.

Important Safety Information

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 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.

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. Please read important information about REMICADE, including full prescribing information at http://www.remicade.com. 

About Centocor

Centocor is harnessing the power of world-leading research and
biomanufacturing to deliver innovative biomedicines that transform patients' lives. Centocor has already brought innovation to the treatment of Crohn's disease, rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. Centocor products have also saved lives in the treatment of heart attacks and have been used to reduce risk of cardiac events in interventional cardiology.

The world leader in monoclonal antibody production and technology, Centocor has brought critical biologic therapies to patients suffering from debilitating immune disorders. Centocor, Inc. is a wholly owned subsidiary of Johnson & Johnson, a worldwide manufacturer of healthcare products.

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