BARCELONA, Spain, 15 June 2007 – Data presented today at the European League Against Rheumatism (EULAR) Annual European Congress of Rheumatology showed that patients with ankylosing spondylitis (AS) who received REMICADE® (infliximab) over two years experienced significant improvement in spinal mobility. In addition, REMICADE-treated patients showed sustained reductions in spinal inflammation through two years as detected by magnetic resonance imaging (MRI).
The recommended dose of REMICADE in AS is 5 mg/kg given as an IV induction regimen at 0, 2 and 6 weeks followed by a 5 mg/kg maintenance regimen every 6 weeks in the United States or every 6-8 weeks in the European Union. AS is a progressive rheumatic disease that leads to inflammation of the back, resulting in pain, stiffness and reduced mobility, which in advanced cases can result in fusion of the vertebrae of the spine ('ankylosis'). Data collected from 279 patients with AS as part of the Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy (ASSERT) trial were analyzed to determine the long-term effect of REMICADE on spinal mobility. The double-blind extension of this 24-week placebo-controlled study utilized the Bath Ankylosing Spondylitis Metrology Index (BASMI) and chest expansion measurements to assess range of motion in patients with AS.
Patients in ASSERT were treated and assessed at six week intervals through week 102. According to the findings, compared with placebo group (N=78), at week 24 the REMICADE-treated patients (N=201) had a greater improvement in BASMI (defined as a change of at least 1 in the BASMI score) scores (-0.7 vs. -0.2, respectively; P = 0.02), and in percent change in chest expansion (44 percent vs. 19 percent, respectively, P = 0.03). Fifty-one percent of REMICADE-treated patients vs. 31 percent of placebo-treated patients achieved a clinically meaningful improvement in BASMI (P < 0.01). The improvement seen at week 24 was maintained through week 102 in those patients who continued in the trial extension (N=161). Furthermore, after crossing over to receive treatment with REMICADE at week 24 following initial treatment with placebo, patients experienced similar improvements in BASMI and chest expansion scores as patients in the REMICADE group at weeks 54, 78 and 102.
“Ankylosing spondylitis can limit spinal mobility and significantly impair a patient’s quality of life. These data demonstrate that treatment with REMICADE improved spinal mobility. Over time, this improvement can be maintained when REMICADE is coupled with physiotherapy,” said Professor Jurgen Braun, M.D., lead physician at the Rheumazentrum Ruhrgebiet and Professor of Rheumatology at the Free University of Berlin. “In studying the same group of patients, REMICADE therapy also had a positive effect on spinal inflammation, a common and debilitating manifestation of ankylosing spondylitis.”
In ASSERT spinal inflammation as detected by MRI was examined. Patients receiving REMICADE showed improvement in MRI Activity scores at week 24, which was sustained through week 102 in those patients who continued in the trial extension (N=161). Patients initially in the placebo group showed no change in MRI Activity scores at week 24, but scores improved after crossing over to receive treatment with REMICADE. The relationship of spinal inflammation as measured by activity scores on MRI to long-term structural damage in AS is unknown.
In ASSERT (Ankylosing Spondylitis [AS] Study for the Evaluation of Recombinant Infliximab Therapy), 279 patients with AS for at least three months, radiographic evidence of sacroiliitis and symptoms of active disease (BASDAI of at least 4 and visual analog scale for spinal pain of at least 4, each on a scale of one to 10) were randomized to receive infusions of REMICADE 5 mg/kg at weeks 0, 2 and 6 and every six weeks thereafter through week 96 (n = 201) or placebo (n = 78). The primary endpoint of the trial was a 20 percent decrease in disease activity score on the Assessment in Ankylosing Spondylitis Response Criteria (ASAS 20) at week 24.
At week 24, placebo patients were crossed over to receive treatment with REMICADE 5 mg/kg at weeks 0, 2 and 6 and every six weeks thereafter and continued on REMICADE through the remainder of the study (96 weeks). Starting at week 36, and continuing through week 96, patients initially randomized to receive REMICADE 5 mg/kg had their dose increased to 7.5 mg/kg if they had a BASDAI of at least 3 in two consecutive evaluations to assess the potential for improved response through increased dosing. Using these rather strict criteria, 106 patients (53 percent) received a dose increase some time after week 30. Nine percent of patients who received REMICADE through week 102 discontinued the study due to adverse events (AEs).
During the study, REMICADE was generally well-tolerated. At week 24, the most commonly reported AEs were upper respiratory tract infections, which occurred at a rate of 15 percent in the placebo group, compared with 14 percent in the REMICADE group. The only laboratory abnormalities that occurred more frequently with REMICADE compared with placebo were asymptomatic liver enzyme test elevations. At week 24, serious (AEs) were reported in 4 percent of REMICADE-treated patients, compared with three percent of patients receiving placebo. AEs were generally mild and were consistent with REMICADE prescribing information.
There were no reports of congestive heart failure, tuberculosis or serious infections in the study population. Three malignancies were reported in three patients during the ASSERT study and included squamous cell skin cancer, lung cancer and breast cancer. Please see “Important Safety Information” below.
About Ankylosing Spondylitis
AS is a painful and progressive form of spinal arthritis and symptoms of inflammatory back pain often first present in people before age 35. It typically begins in the late teens and early twenties and in severe cases may result in fusing spinal vertebrae and may cause structural damage to hips and other joints. Often misdiagnosed as "just back pain" or undifferentiated arthritis, AS is a systemic inflammatory disease that, in addition to its effect on the spine, can affect internal organs, peripheral joints and vision. The Arthritis Research Campaign, estimates that on the European continent, AS prevalence ranges from 0.2 to 1 percent of the entire population. The Spondylitis Association of America estimates that between 350,000 and one million people in the U.S. suffer from Ankylosing Spondylitis.
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), pediatric Crohn’s disease (PCD) 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. Additionally, REMICADE is the only anti-TNF approved in three different therapeutic areas: gastroenterology, rheumatology and dermatology. The safety and efficacy of REMICADE have been well established in clinical trials over the past 15 years and through commercial experience with more than 924,000 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 reducing signs and symptoms and inducing and maintaining clinical remission in adult and pediatric 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. In May 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 August 2006, REMICADE was approved for inhibiting progression of structural damage and improving physical function in patients with psoriatic arthritis. In September 2006, REMICADE was approved for the treatment of adults with chronic, severe (i.e. extensive and/or disabling) plaque psoriasis who are candidates for systemic therapy and when other systemic therapies are medically less appropriate. In October 2006, REMICADE was approved for maintaining clinical remission and mucosal healing in patients with moderately to severely active UC, who have had an inadequate response to conventional therapy.
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 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.
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 drug therapy. REMICADE should be administered in combination with methotrexate or alone in patients who show intolerance to methotrexate or for whom methotrexate 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, methotrexate 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 azathioprine, 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. In May 2007, REMICADE was approved in the EU for the treatment of severe, active Crohn’s disease (CD) in pediatric patients aged 6 to 17 years, who have not responded to conventional therapy including a corticosteroid, an immunomodulator and primary nutrition therapy, or who are intolert to, or have contraindications for, such therapies.
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), UC (5 mg/kg), PCD (5 mg/kg), and PsO (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.
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, 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. Rarely, children and young adults who have been treated for Crohn’s disease with REMICADE in combination with azathioprine or 6-mercaptopurine have developed a rare type of lymphoma, hepatosplenic T cell lymphoma (HSTL), that often results in death. 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 your 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.
Please read important information about REMICADE, including full U.S. prescribing information and Medication Guide, at www.remicade.com. For complete EU prescribing information, please visit www.emea.eu.int.
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 Johnson & Johnson’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 Johnson & Johnson’s Annual Report on Form 10-K for the fiscal year ended December 31, 2006. Copies of this Form 10-K, as well as subsequent filings, are available online at www.sec.gov or on request from Johnson & Johnson. Johnson & Johnson does not undertake to update any forward-looking statements as a result of new information or future events or developments.
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 approximately 33,500 people around the world. The company is based in Kenilworth, N.J., and its Web site is www.schering-plough.com.
SCHERING-PLOUGH DISCLOSURE NOTICE:
The information in this press release contains certain "forward-looking" statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements related to the approval of REMICADE for CD in the EU 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 and a discussion of risks and uncertainties that may impact forward-looking statements, see Schering-Plough's Securities and Exchange Commission filings, including Part II, Item 1A, "Risk Factors" in the company's first quarter 2007 10-Q.