FDA Approves Remicade for Treatment of Chronic Severe Plaque Psoriasis
HORSHAM, Pa., September 27, 2006 -- Centocor, Inc. announced today that the U.S. Food and Drug Administration (FDA) has approved Remicade (infliximab) for the treatment of adult patients 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. The recommended dose is an infusion of 5 mg/kg followed by additional doses at two and six weeks after the first infusion and then every eight weeks thereafter. In the Phase 3 clinical trial EXPRESS, eight out of 10 patients receiving Remicade 5 mg/kg induction therapy achieved 75 percent improvement in psoriasis as measured by Psoriasis Area Severity Index (PASI 75) by week 10. Similar results were seen with EXPRESS II, the second Phase 3 study. These results were maintained by every eight-week Remicade 5 mg/kg maintenance infusions at six months. The majority of patients who continued on this regimen achieved PASI 75 at week 50, the last visit in both studies. More than 1200 patients participated in the two Phase 3 clinical trials.
"The rapidity and consistency with which Remicade can improve clearance of patients’ skin is a major step forward for a patient population where persisting unmet needs in treatment exist," said Alice B. Gottlieb, MD, PhD, Dermatologist-in-Chief, Professor of Dermatology, Tufts-New England Medical Center, and pivotal U.S. study investigator. "As a researcher involved in the clinical investigation of Remicade for the treatment of psoriasis, I’ve seen first-hand its significant results in improving psoriasis in the majority of patients treated."
Psoriasis is an inflammatory disorder characterized by raised, inflamed, red lesions, or plaques, which can cause physical pain and emotional distress. It is estimated that as many as 7.5 million people in the U.S. have psoriasis1, which can present in various forms and can range from mild to severe and disabling. Centocor will expand its educational programs to help dermatologists and their patients achieve the benefits of Remicade and to help manage and minimize the potential risks of biologic therapies, like Remicade.
Data from two multi-center, randomized, double-blind, placebo-controlled trials - EXPRESS and EXPRESS II - served as the primary basis for approval. Both EXPRESS and EXPRESS II showed that a majority of Remicade-treated patients achieved clinically significant levels of skin clearance with induction and every-eight-week maintenance therapy. At week 10 in EXPRESS, 80 percent of patients receiving Remicade 5 mg/kg achieved PASI 75 versus three percent of patients receiving placebo (P < 0.001). At week 10 in EXPRESS II, 75 percent of patients receiving Remicade 5 mg/kg achieved PASI 75 versus two percent of patients receiving placebo (P < 0.001).
During the controlled periods in EXPRESS and EXPRESS II, adverse events (AEs) occurred at a higher incidence in the Remicade groups compared with the placebo groups. In the EXPRESS study, there were more serious AEs, including one fatal infection, in the Remicade group compared with placebo group. In the EXPRESS II study, serious AE rates were similar in the Remicade 5 mg/kg and placebo groups. The only clinically significant laboratory abnormalities that occurred more frequently in the Remicade groups compared with the placebo groups were elevated liver enzyme tests. AEs observed in these studies were generally consistent with those described in the prescribing information, including the risk of serious infections. Please see "Important Safety Information" below.
"New biologic treatment options are needed in our struggle to more effectively manage all patients with this lifelong chronic condition, particularly those that have severe disease," said Alan Menter, MD, Chairman, Division of Dermatology, Medical Center, and lead U.S. study investigator. "The approval of Remicade offers dermatologists a treatment option that has been clinically proven to rapidly and dramatically clear the skin of patients with a high disease burden."
Psoriasis is most commonly diagnosed between the ages of 20 and 30, striking in the prime of people’s lives, and the extent of skin involvement varies from mild to severe and disabling. People with severe psoriasis may have large areas of their body covered by lesions, which may crack and bleed. The pain and embarrassment associated with such skin lesions may prevent people from participating in social and work-related activities, and the physical and mental effects of psoriasis have been compared to those of other chronic illnesses such as rheumatoid arthritis, hypertension, heart disease, diabetes and depression. Skin lesions associated with psoriasis often result in feelings of sadness, despair, guilt and anger, as well as in low self- esteem. A person’s sense of self-worth can be affected, and in some cases, this emotional turmoil can lead to depression.
"Psoriasis is a serious disease that is often misunderstood. There’s physical pain such as itching and cracking of lesions, as well as the emotional hurt of being stared at or having to explain several times a day what psoriasis is and that it’s not contagious. These are things that some patients must contend with each day," said Gail Zimmerman, President and CEO, National Psoriasis Foundation. "The approval of Remicade is a much-needed addition for patients living with severe psoriasis."
Remicade is the first and only anti-TNF-alpha treatment to receive 13 FDA approvals across inflammatory diseases in gastroenterology, rheumatology and dermatology, and has now been used to treat more than 800,000 patients worldwide, more than all other anti-TNF agents combined. Remicade is an advanced biologic treatment for chronic severe plaque psoriasis, requiring as few as six treatments a year after an initial three treatments.
The European Infliximab for Psoriasis [Remicade] Efficacy and Safety Study (EXPRESS) was a Phase 3, multi-center, randomized, double-blind, placebo- controlled trial that evaluated the safety and efficacy of Remicade induction and maintenance therapy in 378 adult patients with chronic, stable plaque psoriasis involving at least 10 percent body surface area (BSA), a minimum PASI score of 12 and 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.
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 the placebo group were elevated liver enzyme tests. There were more serious AEs (six percent), including one fatal infection, in the Remicade group than in the placebo group (three 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
The Evaluation of Infliximab for Psoriasis in a [Remicade] Efficacy and Safety Study (EXPRESS II) was a Phase 3, multi-center, randomized, double- blind, placebo-controlled trial that evaluated the safety and efficacy of Remicade in 835 adult patients with chronic, stable plaque psoriasis involving at least 10 percent BSA, a minimum PASI score of 12 and 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.
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 with 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 the placebo group were elevated liver enzyme tests. Serious AEs occurred at rates of two percent in the placebo group, three percent in the 5 mg/kg group and one 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.
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.
Remicade is the global market leader among anti-tumor necrosis factor alpha (TNF-alpha) therapies and is the only anti-TNF-alpha treatment approved in three different therapeutic areas: gastroenterology, rheumatology and dermatology. Remicade has demonstrated broad clinical utility 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). The safety and efficacy of Remicade have been well established in clinical trials over the past 14 years and with more than 800,000 patients treated worldwide through commercial experience.
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 addition, 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.
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 (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.
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.
Please read the Medication Guide for Remicade and discuss it with your doctor.
1. National Institute of Arthritis and Musculoskeletal and Skin Disorders. Questions and Answers About Psoriasis. U.S. Department of Health and Human Services, National Institutes of Health; 2003. NIH Publication No. 03-5040.
Source: Centocor, Inc.
Posted: September 2006
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