REMICADE(R) Receives EU Approval as Second-Line Therapy for Patients with Crohn's Disease (1)

HORSHAM, Pennsylvania and KENILWORTH, New Jersey, October 9 /PRNewswire/ --

-- Revised Labeling Allows Crohn's Patients to Benefit from REMICADE When They Do Not Respond to a Full and Adequate Course of Therapy with a Corticosteroid and/or an Immunosuppressant

Centocor, Inc. and Schering-Plough Corporation (NYSE: SGP) today announced that the European Commission has approved a label change for REMICADE(R) (infliximab) for use as a second-line therapy for the treatment of severe, active Crohn's disease (CD) in patients who have not responded despite a full and adequate course of therapy with a corticosteroid and/or an immunosuppressant, or who are intolerant to or have medical contraindications for such therapies. This approval follows a positive opinion granted in July by the Committee for Medicinal Products for Human Use (CHMP) for the European Medicines Agency (EMEA).

REMICADE was previously approved in the EU as a third-line therapy for the treatment of severe, active Crohn's disease in patients who have not responded despite a full and adequate course of therapy with a corticosteroid and an immunosuppressant. Crohn's disease is a debilitating condition that causes inflammation of the gastrointestinal tract, typically resulting in symptoms such as diarrhea, fever, abdominal pain and weight loss and, complications including intestinal obstruction and fistulas that can result in the need for repeated surgical procedures.

"The approval of REMICADE as a second-line therapy offers a new option to patients suffering from active Crohn's disease for which other therapies do not provide relief," said Robert Spiegel, MD, chief medical officer and senior vice president, Schering-Plough Research Institute.

"Crohn's disease significantly impacts the quality of life for patients suffering from this condition," said Jean-Frederic Colombel, Professor of Gastroenterology, Hospital Huriez, University Hospital of Lille, France. "Now physicians have the option to treat these patients with REMICADE earlier in the course of their disease following a poor or inadequate response to other therapies."

The CHMP positive opinion and approval are based on the ACCENT I (A Crohn's disease Clinical trial Evaluating infliximab in a New long-term Treatment regimen) and GETAID (Groupe d'Etude Therapeutique des Affections Inflammatoires du Tube Digestif) studies, as well as the TREAT (Therapy, Resource, Evaluation and Assessment Tool) registry and additional post-marketing data.

About ACCENT I

Patients enrolled in the ACCENT I trial were given a single REMICADE 5 mg/kg infusion. Those who responded at week two were randomly assigned to three treatment groups. One group received placebo at weeks two and six followed by repeat infusions of placebo every eight weeks. The second group received infusions of 5 mg/kg of REMICADE at weeks two and six followed by subsequent infusions at the same dose every eight weeks. A third group received infusions of 5 mg/kg of REMICADE at weeks two and six followed by repeat infusions of 10 mg/kg every eight weeks thereafter. Infusions continued for all treatment groups through week 46. The co-primary endpoints were the proportion of patients who responded at week two and were still in remission at week 30 and the time to loss of response through week 54 in patients who responded. Response and remission were assessed using the Crohn's disease activity index (CDAI). Response was defined as a decrease of >= 25 percent and >=70 points in CDAI score. Remission was defined as CDAI score of less than 150.

Researchers found that 57 percent of patients (311/545) responded to a single infusion of REMICADE at two weeks of treatment. Among responders, significantly more patients receiving maintenance treatment with REMICADE 5 mg/kg achieved clinical remission at week 30 (39 percent) compared to placebo maintenance patients (25 percent). Additionally, patients in the REMICADE maintenance groups had a longer time to loss of response than patients in the placebo maintenance group.

A significantly greater proportion of patients receiving maintenance therapy with REMICADE were in clinical remission and able to reduce or eliminate steroid use compared to those treated with placebo. At week 54, more than twice as many patients in the REMICADE 5 mg/kg maintenance group were in remission and had discontinued steroid use (25 percent) compared to patients treated with a single infusion of REMICADE 5 mg/kg followed by placebo (11 percent).

REMICADE safety in the study was consistent with that seen in other trials of REMICADE for Crohn's disease and rheumatoid arthritis. In particular, the incidence of serious infections was similar across treatment groups.

About GETAID

GETAID, the Groupe d'Etude Therapeutique des Affections Inflammatoires du Tube Digestif study, which translates into English as "Group Therapeutic Study of the Inflammatory Affections of the Digestive Tract," an investigator-initiated, randomized, multicenter, placebo-controlled study evaluated the combination of Azathioprine or 6-mercaptopurine (AZA or 6-MP) in combination with infliximab as an induction regimen (3 infusions at 0, 2 and 6 weeks), compared with AZA or 6-MP alone in patients with steroid-dependent CD. CD patients who had an active disease despite prednisone (>= 10 mg/d) given for more than 6 months were eligible for the trial. All patients were treated with AZA (2-3 mg/kg/d) or 6MP (1-1.5 mg/kg/d); patients were randomized to receive either 3 infusions of infliximab (5 mg/kg) or placebo at weeks 0, 2 and 6.

During the 54 weeks of the study, if clinical remission was achieved (CDAI less than 150), steroids were tapered according to a standardized scheme; in patients who experienced a relapse, the dose of steroids was increased until a new remission was achieved, and then tapered. The primary end-point was remission off steroids at week 54. The percentage of patients in remission off steroids was higher in the infliximab group than in the placebo group at week 12 (75% vs. 38%; P<0.001), at week 24 (57% vs. 29%; P=0.003), and at week 54 (40% vs. 22%; P=0.04). Severe adverse events occurred in 2 and 4 patients in the infliximab and placebo groups, respectively.

About TREAT

Data was collected from the Crohn's Therapy, Resource, Evaluation and Assessment Tool (TREAT), a patient registry established to study long-term safety of REMICADE in CD. At the time of this analysis, April 2005, the registry included 6,290 adult CD patients who were divided into two groups according to treatment. Approximately 51 percent (3,235) of patients in the registry were treated with REMICADE and 49 percent (3,055) received other therapies. Patients in the REMICADE group received REMICADE within 12 weeks prior to registration, were scheduled to receive REMICADE within 30 days of registration, or received REMICADE at some other point in the registry.

Approximately 25,000 REMICADE infusions have been collected in the TREAT registry, with an infusion reaction rate of 4 percent of infusions (where of .11 percent were serious). The overall rate of infusion reactions was consistent with the rate observed in complex clinical trials of REMICADE

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