REMICADE(R) Receives Approval in European Union for Dosing Flexibility in the Treatment of Rheumatoid Arthritis

HORSHAM, Pennsylvania., and KENILWORTH, New Jersey, March 2 /PRNewswire/ --

- Revised Labeling Will Allow RA Patients to Receive Adjusted Dosage To Maximize Efficacy and Symptom Relief

Centocor, Inc. and Schering-Plough Corporation (NYSE: SGP) today announced that the European Commission (EC) has approved a label extension for REMICADE(R) (infliximab) allowing for greater dosing flexibility in the treatment of rheumatoid arthritis (RA). The EC approval follows a positive opinion by the Committee for Medicinal Products for Human Health (CHMP) of the European Medicines Agency (EMEA) that was received in November 2006.

For patients who had an incomplete response to initial combination treatment with methotrexate and REMICADE 3 mg/kg, the dose titration label extension will permit physicians to increase the REMICADE dose stepwise from 3 mg/kg up to 7.5 mg/kg every 8 weeks, or to treat patients with 3 mg/kg as often as every 4 weeks.

"Offering physicians the option to adjust dosing is welcome news for European rheumatologists who regularly manage rheumatoid arthritis patients," said Iain B. McInnes, FRCP, PhD, Professor of Experimental Medicine, University of Glasgow, Honorary Consultant Rheumatologist, Centre for Rheumatic Diseases, Glasgow Royal Infirmary, Glasgow, United Kingdom.

"The European Commission approval of the dose titration label extension will allow physicians greater flexibility to adjust the dose of REMICADE to ensure rheumatoid arthritis patients are getting optimal treatment," said Robert J. Spiegel, MD, chief medical officer, Schering-Plough Research Institute. "This latest regulatory milestone further validates the safety and efficacy profile of REMICADE for the treatment of patients with rheumatoid arthritis."

The EC approval for the dose titration label extension is based on data from the Safety Trial for Rheumatoid Arthritis with REMICADE (infliximab) Therapy (START), a randomized, multi-center, double-blind, three-arm, parallel-group, placebo-controlled study involving 1,082 treated patients with active RA. In one study arm beginning at week 22 (group 2, n=329), eligible patients that met predefined criteria for lack of response or loss of response were allowed to dose titrate with 1.5 mg/kg increments from 3 mg/kg up to 9 mg/kg. The majority (67 percent) of these patients did not require any dose titration. Of the patients who required a dose titration, 80 percent achieved clinical response and the majority (64 percent) of these required only one adjustment of 1.5 mg/kg.

About Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic, debilitating inflammatory disease that causes pain, swelling, stiffness, and loss of function in the joints. Symptoms of RA include inflammation of the joints, swelling, difficulty moving, and pain. The most commonly affected joints are the hands and feet. The joint pain of RA can impact a patient's ability to perform normal daily activities, limit job opportunities, and make family and household responsibilities a challenge. RA afflicts more than 9.7 million people worldwide; according to the World Health Organization, the incidence of RA in Europe is expected to increase over the next decade as the population ages.

About START

The START study was undertaken to better characterize the safety profile of REMICADE plus methotrexate in combination with background treatments during one year in a population of RA patients who may have existing comorbidities. The primary objective of this study was to assess the relative risk of serious infections within the first 22 weeks after treatment with REMICADE in combination with methotrexate, in RA patients that had demographics reflective of patients seen in clinical practice. In addition, the study evaluated the effect of escalating doses in those patients who exhibited an incomplete response to the lowest approved dose, 3 mg/kg given every 8 weeks.

In START, patients with active RA despite receiving MTX were randomly assigned to receive infusions of placebo (group 1, n _ 363), REMICADE 3 mg/kg (group 2, n _ 360), or REMICADE 10 mg/kg (group 3, n _ 361) at weeks 0, 2, 6, and 14. At week 22, patients in placebo group 1 began receiving REMICADE 3 mg/kg every 8 weeks, and patients in group 3 continued to receive REMICADE 10 mg/kg every 8 weeks. In group 2 (n=329), patients with an inadequate response received increasing doses of REMICADE at 1.5 mg/kg increments from 3 mg/kg up to 9 mg/kg, administered every 8 weeks. The majority (67 percent) of patients in group 2 did not require any dose titration. Of the patients who required a dose titration, 80 percent achieved clinical response and the majority (64 percent) of these required only one adjustment of 1.5 mg/kg.

Results of the START study found that the risk of serious infections in patients receiving REMICADE 3 mg/kg plus methotrexate was similar to that in patients receiving methotrexate alone. Patients receiving the unapproved induction regimen of REMICADE 10 mg/kg plus methotrexate followed by a 10 mg/kg maintenance regimen had an increased risk of serious infections through week 22. Through week 54, 1 patient in group 1, 2 patients in group 2, and 4 patients in group 3 developed active tuberculosis. During weeks 22-54, serious adverse events among subjects in group 2 that did not dose titrate versus subjects that did dose titrate were 4 percent and 6 percent, respectively; serious infections occurred in 0.5 percent and 0 percent of subjects, respectively.

About REMICADE

REMICADE is a monoclonal antibody that specifically targets TNF-alpha, which has been shown to play a role in Crohn's disease (CD), rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), ulcerative colitis (UC) and psoriasis (PsO). 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 and through commercial experience with nearly 840,000 patients treated worldwide.

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/or 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 adults when the response to previous disease-modifying anti-rheumatic drugs therapy has been inadequate. REMICADE should be administered in combination with MTX or alone in patients who show intolerance to MTX or for whom MTX is contraindicated. REMICADE is also 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, MTX or PUVA (psoralen plus ultraviolet A light).

In February 2006, REMICADE was approved in the EU for the treatment of moderately-to-severely active UC in patients who have had an inadequate response to conventional therapy, including corticosteroids and 6-MP or AZA, or who are intolerant to or have medical contraindications for such therapies. This approval made REMICADE the first and only biologic therapy approved to treat moderate-to-severe UC in the EU.

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), PsA (5 mg/kg), psoriasis (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 to 8 weeks, following a standard induction regimen that requires treatment at weeks 0, 2 and 6. In carefully selected patients with RA who have tolerated three initial two-hour infusions of REMICADE, consideration may be given to administering subsequent infusions over a period of not less than one hour. Shortened infusions at doses greater than 6 mg/kg have not been studied.

Furthermore, if an RA patient has an inadequate response or loses response after initial treatment with REMICADE, consideration may be given to increase the dose step-wise by approximately 1.5 mg/kg, up to a maximum of 7.5 mg/kg every 8 weeks. Alternatively, administration of 3 mg/kg as often as every 4 weeks may be considered. If adequate response is achieved, patients should be continued on the selected dose or dose frequency. Continued therapy should be carefully reconsidered in patients who show no evidence of therapeutic benefit within the first 12 weeks of treatment or after the dose has been adjusted.

REMICADE treatment is to be initiated and supervised by qualified physicians experienced in the diagnosis and treatment of rheumatoid arthritis, inflammatory bowel diseases, ankylosing spondylitis, psoriatic arthritis or psoriasis. REMICADE infusions should be administered by qualified healthcare professionals trained to detect any infusion related issues. Patients treated with REMICADE should be given a package leaflet and a special alert card.

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.

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 TB 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, flu or warm, red or painful skin while taking REMICADE, tell your doctor right away. Also, tell your doctor if you are scheduled to receive a vaccine or if, you have lived in a region where histoplasmosis or coccidioidomycosis is common.

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, psoriatic arthritis, or plaque psoriasis 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. Children and young adults who have been treated for Crohn's disease with REMICADE have developed a rare type of lymphoma that often results in death. These patients also were receiving drugs known as azathioprine or 6-mercaptopurine. 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 or if you have a lung disease called chronic obstructive pulmonary disease (COPD).

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, swelling of your ankles or feet, or sudden weight gain.

Reactivation of hepatitis B virus has been reported in patients who are carriers of this virus and are taking TNF blockers, such as REMICADE. Some of these cases have been fatal. Tell your doctor if you know or think you may be a carrier of hepatitis B virus or if you experience signs of hepatitis B infection, such as feeling unwell, poor appetite, tiredness, fever, skin rash and/or joint pain.

There have been rare cases of serious liver injury in people taking REMICADE, some fatal. Tell your doctor if you have liver problems and 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, visual disturbances or seizures while taking REMICADE.

Allergic reactions, some severe have been reported during or after infusions with REMICADE. Signs of an allergic reaction include hives, difficulty breathing, chest pain, high or low blood pressure, swelling of face and hands, and fever or chills. Tell you doctor if you have experienced a severe allergic reaction. The most common side effects of REMICADE are: respiratory infections, such as sinus infections and sore throat, headache, rash, coughing, and stomach pain.

For complete EU prescribing information, please visit www.emea.eu.int.

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, psoriatic arthritis, ulcerative colitis, pediatric Crohn's disease and psoriasis.

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.

This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could vary materially from the Company's expectations and projections. Risks and uncertainties include general industry conditions and competition; economic conditions, such as interest rate and currency exchange rate fluctuations; technological advances and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approvals; domestic and foreign health care reforms and governmental laws and regulations; and trends toward health care cost containment. A further list and description of these risks, uncertainties and other factors can be found in Exhibit 99 of the Company's Annual Report on Form 10-K for the fiscal year ended January 1, 2006. Copies of this Form 10-K, as well as subsequent filings, are available online at www.sec.gov or on request from the Company. The Company does not undertake to update any forward-looking statements as a result of new information or future events or developments.

About Schering-Plough

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 contains certain "forward-looking" statements within the meaning of the Securities Reform Act of 1995, including statements related 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, current and future branded, generic or over-the-counter competition and the regulatory process, among other uncertainties. For further details and a discussion of risks and uncertainties that may affect forward-looking statements, see the company's Securities and Exchange Commission filings, including the company's second quarter 2006 10-Q.

Schering-Plough Media: Catherine Cantone +1-908-298-3944 Gail Thornton +1-908-298-5313 Investors: Alex Kelly +1-908-298-7450 Robyn Brown +1-908-298-7417 Centocor Michael Parks +1-215-325-4010

Web site: http://www.schering-plough.com