REMICADE(R) Receives EU Approval as Monotherapy for Treatment of Psoriatic Arthritis

KENILWORTH, New Jersey, July 26 /PRNewswire/ --

- New Label Reflects Clinical Efficacy of REMICADE Demonstrated by Improvement in Joint Involvement and Significant Skin Clearance

Schering-Plough Corporation (NYSE: SGP) today announced that the European Commission has approved the use of REMICADE(R) (infliximab) as monotherapy in the treatment of active and progressive psoriatic arthritis (PsA) in patients who show intolerance to methotrexate or for whom methotrexate is contraindicated. This label extension follows a positive opinion granted in June by the Committee for Medicinal Products for Human Use (CHMP), for the European Medicines Agency (EMEA).

REMICADE, in combination with methotrexate, originally received approval for the treatment of active and progressive psoriatic arthritis in patients who have responded inadequately to disease-modifying anti-rheumatic drugs in October 2004. Psoriatic arthritis is a chronic, autoimmune inflammatory condition involving the joints and the skin.

"For those psoriatic arthritis patients for whom the use of methotrexate is not appropriate, the approval of REMICADE for use as a monotherapy offers a new treatment option for their disease," said Robert Spiegel, MD, chief medical officer and senior vice president, Schering-Plough Research Institute.

The REMICADE PsA extension is based on one-year data from Infliximab Multi-National Psoriatic Arthritis Controlled Trial 2 (IMPACT 2), a Phase III clinical study of 200 patients, with active PsA; and two-year data from the original IMPACT Trial, upon which the initial approval of REMICADE in PsA was based. In the IMPACT 2 trial, the primary endpoint of joint improvement was met in REMICADE-treated patients. At week 24 of treatment, 54 percent of patients achieved an ACR 20 response (a 20 percent collective improvement in rheumatoid arthritis symptoms) 41 percent had an ACR 50 response and 27 percent experienced an ACR 70 response. Furthermore, at week 54 of treatment, 53 percent of REMICADE-treated patients achieved an ACR 20 response; with 33 percent and 20 percent experiencing ACR 50 and ACR 70 responses, respectively.

Also, a Psoriasis Area and Severity Index score of 75 (PASI 75) was seen in 60 percent of REMICADE-treated patients at week 24, with nearly 49 percent of REMICADE patients maintaining this response at week 54 of therapy. A PASI 75 score reflects a 75 percent improvement in disease symptoms. The prescribing information for REMICADE has been revised to include these latest trial results specific to skin clearance.

"The joint involvement and often painful skin lesions associated with psoriatic arthritis, places an extraordinary burden on patients with this potentially progressive disease," said Douglas Veale, MD, Consultant Rheumatologists, University College of Dublin and St. Vincent's Hospital, Ireland. "In addition to the response of the joints, the PASI 75 response demonstrated in the IMPACT 2 trial should be a new treatment goal sought by rheumatologists who work with these psoriatic arthritis patients."

In the IMPACT and IMPACT 2 trials, patients treated with REMICADE saw significant improvements in standard measures of disease activity; including number of swollen joints, number of painful and/or tender joints, dactylitis (finger or toe inflammation) and enthesopathy (inflammation involving the attachment of a tendon or ligament to bone.) Also, REMICADE-treated patients in both trials saw disease improvement as early as week 2, with significant clinical response maintained through week 98 and 54 of treatment in IMPACT and IMPACT 2, respectively. REMICADE efficacy was demonstrated in both trials, with or without concomitant use of methotrexate.

Patients treated with REMICADE also saw significant improvements in physical function and health-related quality of life as measured with standardized questionnaires.

Elevated transaminase levels, which were noted with infliximab treatment during the first six months of IMPACT 2 and first year of IMPACT, were not disproportionately increased with an additional six months to one year of maintenance therapy. The elevations generally resolved with interruption or at times with continuation of therapy and were not associated with concomitant elevations in bilirubin or liver failure. While mild-to-moderate infusion reactions occurred, the PsA studies through one to two years of maintenance treatment demonstrated that there were no serious infusion reactions, delayed hypersensitivity or possible anaphylactic reactions.

Please see the Important Safety Information for REMICADE below.

While PsA can develop at any age, onset usually occurs in middle-age, typically in adults between the ages of 30 and 50. Men and women are affected equally. Symptoms include stiffness, pain, swelling and tenderness of the joints and surrounding soft tissue, reduced range of motion, morning stiffness, and tiredness. Other symptoms include psoriatic skin lesions, nail changes, including pitting (small indentations in the nail) or lifting of the nail.

REMICADE is a monoclonal antibody that specifically targets TNF-alpha, which has been shown to play a role in Crohn's disease (CD), ulcerative colitis (UC), rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA) and psoriasis. REMICADE is the global market leader among anti-tumor necrosis factor alpha (TNF-alpha) therapies and the only agent approved for the treatment of both RA and CD in North America, the EU and Japan. The safety and efficacy of REMICADE have been well established in clinical trials over the past 14 years. REMICADE has been used to treat over 770,000 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. Moreover, on May 19, 2006, REMICADE was approved for reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients with moderately to severely active Crohn's disease who have had an inadequate response to conventional therapy. This approval establishes REMICADE as the first and only biologic therapy approved for the treatment of PCD.

In the EU, REMICADE is indicated for the treatment of severe, active CD in patients who have not responded despite a full and adequate course of therapy with a corticosteroid and an immunosuppressant; or who are intolerant to or have medical contraindications for such therapies. REMICADE also is indicated for the treatment of fistulizing, active CD in patients who have not responded despite a full and adequate course of therapy with conventional treatment (including antibiotics, drainage and immunosuppressive therapy).

For RA patients in the EU, REMICADE, in combination with methotrexate, is indicated for the reduction of signs and symptoms as well as the improvement in physical function in patients with active disease when the response to disease-modifying drugs, including methotrexate, has been inadequate, and in patients with severe, active and progressive disease not previously treated with methotrexate or other DMARDs. In these patient populations, a reduction in the rate of the progression of joint damage, as measured by X-ray, has been demonstrated.

In the EU, REMICADE is also indicated for the treatment of AS in patients who have severe axial symptoms, elevated serological markers of inflammatory activity and who have responded inadequately to conventional therapy. REMICADE is also approved for the treatment of active and progressive PsA in patients who have responded inadequately to disease modifying anti-rheumatic drugs. Additionally, in September 2005, REMICADE was approved in the EU 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 PUVA (psoralen plus ultraviolet A light).

REMICADE is the only anti-TNF biologic therapy available as an IV form. 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), UC (5 mg/kg), PsA (5 mg/kg) and psoriasis (5 mg/kg) and, 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 to 8 weeks, following a standard induction regimen that requires treatment at weeks 0, 2 and 6.

Centocor discovered REMICADE and has exclusive marketing rights to the product in the United States. Schering-Plough markets REMICADE in all countries outside of the United States, except in Japan and parts of the Far East where Tanabe Seiyaku, Ltd. markets the product and in China where Xian-Janssen markets REMICADE.

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.

Rare postmarketing cases of hepatosplenic T-cell lymphoma have been reported in adolescent and young adult patients with Crohn's disease treated with REMICADE. This rare type of T-cell lymphoma has a very aggressive disease course and is usually fatal. All of these hepatosplenic T-cell lymphomas with REMICADE have occurred in patients on concomitant treatment with azathioprine or 6-mercaptopurine. A risk for the development for hepatosplenic T-cell lymphoma in patients treated with REMICADE cannot be excluded.

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 US prescribing information, at www.remicade.com. For complete EU prescribing information, please visit www.emea.eu.int.

Schering-Plough is a global science-based health care company with leading prescription, consumer and animal health products. Through internal research and collaborations with partners, Schering-Plough discovers, develops, manufactures and markets advanced drug therapies to meet important medical needs. Schering-Plough's vision is to earn the trust of the physicians, patients and customers served by its more than 32,000 people around the world. The company is based in Kenilworth, N.J., and its Web site is http://www.schering-plough.com.

SCHERING-PLOUGH DISCLOSURE NOTICE: The information in this press release includes certain "forward-looking statements" within the meaning of the Securities Litigation Reform Act of 1995, including statements relating to REMICADE and the potential market for REMICADE. Forward-looking statements relate to expectations or forecasts of future events. Schering-Plough does not assume the obligation to update any forward-looking statement. Many factors could cause actual results to differ materially from Schering-Plough's forward-looking statements, including market forces, economic factors, product availability, patent and other intellectual property protection, current and future branded, generic or over-the-counter competition, the regulatory process, and any developments following regulatory approval, among other uncertainties. For further details about these and other factors that may impact the forward-looking statements, see Schering-Plough's Securities and Exchange Commission filings, including Item 1A. Risk Factors in the Company's 2005 10-K.

Web site: http://www.schering-plough.com http:// www.remicade.com http:// www.emea.eu.int