New One-Year Phase 3 Study Results Show Anti-TNF SIMPONI® Maintained Clinical Response In Treatment Of Moderately To Severely Active Ulcerative Colitis

LAS VEGAS, Oct. 22, 2012 /PRNewswire/ -- New Phase 3 study findings showed significantly more patients with moderately to severely active ulcerative colitis (UC) who responded to induction therapy with subcutaneously administered SIMPONI^® (golimumab) maintained clinical response through week 54, the primary endpoint of the study, compared with patients receiving placebo.  Investigators will report clinical response, clinical remission and mucosal healing results through one year from the Janssen Research & Development, LLC (Janssen)-sponsored Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment (PURSUIT)-Maintenance investigational study of the anti-tumor necrosis factor (TNF)-alpha therapy during an oral presentation at the annual meeting of the American College of Gastroenterology (ACG).  In May, SIMPONI induction data were reported at an international gastroenterology congress, and in July, Janssen announced the submission of applications to the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) seeking approval of SIMPONI for the treatment of adult patients with moderately to severely active UC.     

"Data from PURSUIT-Maintenance, the companion study to PURSUIT-Induction, showed patients responding to SIMPONI subcutaneous induction therapy who were randomized to every-four-week subcutaneous maintenance therapy demonstrated continuous clinical response through one year," said the study's lead investigator, William Sandborn, MD, professor and chief of the Division of Gastroenterology at the University of California, San Diego (UCSD) School of Medicine, and director of the UC San Diego Inflammatory Bowel Disease Center.  "Findings from this rigorous clinical program showed patients who responded to SIMPONI induction therapy and went on to receive SIMPONI maintenance therapy also achieved clinical remission and mucosal healing, important measures of disease activity in the treatment of moderately to severely active ulcerative colitis."  

In the PURSUIT-Maintenance trial, patients in response to SIMPONI induction therapy were randomized to treatment with subcutaneous SIMPONI 50 mg, SIMPONI 100 mg or placebo every four weeks.  The primary endpoint was clinical response through week 54.  All patients were assessed for UC disease activity using the Mayo score at week 30 and at week 54 and by partial Mayo score every four weeks (loss of response was confirmed by endoscopy).  Patients not in response at any point in the study were treated as non-responders.  Therefore, a patient who maintained response was in a state of continuous clinical response through week 54.  

Investigators reported that 47 percent of patients receiving SIMPONI 50 mg and 51 percent of patients receiving SIMPONI 100 mg demonstrated maintenance of clinical response through week 54 compared with 31 percent of patients receiving placebo (P = 0.01 and P < 0.001, respectively).  Clinical response was defined using the Mayo score, a 12-point clinical assessment and colonoscopy-based measure of disease activity, which assesses improvement in symptoms based on rectal bleeding, stool frequency, endoscopic findings and a physician's global assessment.

Secondary endpoints included clinical remission and mucosal healing at both weeks 30 and 54 among patients who were in clinical response at week 0 of the maintenance study; maintained clinical remission at both weeks 30 and 54 among patients who were in clinical remission at week 0 of the maintenance trial; and, clinical remission with corticosteroid discontinuation at week 54 among patients in response to induction therapy and receiving corticosteroids at week 0 of the maintenance study.  A significantly higher proportion of patients in response to SIMPONI induction therapy who received SIMPONI 100 mg achieved clinical remission (29 percent) and mucosal healing (44 percent) at both week 30 and  week 54 compared with patients receiving placebo (15 percent [P = 0.003]; 27 percent [P = 0.001], respectively).  Improvements in the SIMPONI 50 mg group for clinical remission (24 percent) and mucosal healing (42 percent) at both weeks 30 and 54 were greater, though not significantly, compared with the placebo group (15 percent; 27 percent, respectively).  Among the study patients who had achieved clinical remission at week 0, the proportions of patients in clinical remission at both week 30 and week 54 were greater, though not significantly, in the SIMPONI 50 mg and SIMPONI 100 mg groups (37 percent and 40 percent, respectively) compared with the placebo group (24 percent).  Corticosteroid-free remission at week 54 among patients in response to induction therapy and receiving corticosteroids at week 0 was reported in 28 percent of patients receiving SIMPONI 50 mg and 23 percent of patients receiving SIMPONI 100 mg compared with 18 percent of patients receiving placebo, these results were not statistically significant.

Through week 54, the proportions of randomized patients experiencing at least one adverse event were: 73 percent (SIMPONI 50 mg group), 73 percent (SIMPONI 100 mg group) and 66 percent (placebo group); serious AEs were: eight percent (SIMPONI 50 mg group), 14 percent (SIMPONI 100 mg group) and eight percent (placebo group).  Among all treated patients, there were four cases of active tuberculosis (TB) reported in SIMPONI-treated patients through week 54, and malignancy rates were 0 percent, 0.3 percent and 0.4 percent in the SIMPONI 50 mg, SIMPONI 100 mg and placebo groups, respectively.  Three deaths were reported in the SIMPONI-treated patients through week 54.  The safety of SIMPONI in the treatment of UC was consistent with the safety profile of SIMPONI in labeled rheumatologic indications.

About the PURSUIT Trial

PURSUIT is a Phase 3 multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of SIMPONI in adults with moderately to severely active UC.  The PURSUIT-Maintenance trial draws from patients who participated in the induction phase of PURSUIT evaluating either a subcutaneous (SC) or intravenous (I.V.) formulation of SIMPONI. All induction trial patients had failed to respond to or tolerate treatment with 6-mercaptopurine (6-MP), azathioprine (AZA), corticosteroids and/or 5-aminosalicylate (5-ASA), or were corticosteroid dependent.  Study participants were naive to treatment with TNF-inhibitors and had a baseline Mayo score between six and 12 and endoscopic subscore greater than or equal to two.  Data from the PURSUIT-SC induction trial were presented earlier this year.

PURSUIT-Maintenance used a randomized withdrawal study design in which patients in clinical response following SIMPONI induction therapy were randomized to placebo or to continue on treatment with SIMPONI.  Overall, 1,228 patients were enrolled from the PURSUIT-IV and PURSUIT-SC induction studies into PURSUIT-Maintenance.  Of those, 464 induction responders were randomized to receive subcutaneous SIMPONI 50 mg or SIMPONI 100 mg or placebo at week 0 and every four weeks thereafter.  Responders to placebo induction therapy (N=129) continued receiving placebo and induction trial non-responders (N=635) received subcutaneous SIMPONI 100 mg every four weeks upon entering the study. 

The primary endpoint was clinical response through week 54.  All patients were assessed for UC disease activity using the Mayo score at week 30 and at week 54 and by partial Mayo score every four weeks (loss of response was confirmed by endoscopy).  Patients not in response at any point in the study were treated as non-responders.  Therefore, a patient who maintained response was in a state of continuous clinical response through week 54.  Secondary endpoints included clinical remission and mucosal healing at both weeks 30 and 54 among patients who were in clinical response at week 0 of the maintenance study; maintained clinical remission at both weeks 30 and 54 among patients who were in clinical remission at week 0 of the maintenance trial; and, clinical remission with corticosteroid discontinuation at week 54 among patients in response to induction therapy and receiving corticosteroids at week 0 of the maintenance study.  A fixed sequence testing procedure was applied for the primary endpoint and within each major secondary endpoint, where endpoints were tested in hierarchical fashion.  Safety data was summarized for the 464 randomized SIMPONI induction responders; however, selected events of interest were summarized for all 1,228 treated patients.

About Ulcerative Colitis

Ulcerative colitis (UC), a chronic inflammatory bowel disease (IBD) affecting nearly 700,000 people in the U.S., is marked by the inflammation and ulceration of the colonic mucosa, or innermost lining, which may lead to bloody stools, severe diarrhea and frequent abdominal pain.  Tiny open sores, or ulcers, form on the surface of the lining where they bleed and produce pus and mucus.  Symptoms of the disease may lead to loss of appetite, subsequent weight loss and fatigue.  On average, people are diagnosed with UC in their mid-30s, but the disease can occur at any age.¹  Between 25 and 40 percent of people living with UC will require surgery at some point in their life.²  UC is a chronic disease, and there is no cure.  Although progress has been made in IBD research, researchers do not know what causes this disease.¹ 

About SIMPONI^® (golimumab)

SIMPONI is a human monoclonal antibody that targets and neutralizes excess TNF-alpha, a protein that when overproduced in the body due to chronic inflammatory diseases can cause inflammation and damage to bones, cartilage and tissue.  SIMPONI is approved in 57 countries for adult rheumatologic indications, including the United States where SIMPONI received FDA approval in April 2009 for the treatment of moderately to severely active rheumatoid arthritis (RA) with the medicine methotrexate, active psoriatic arthritis alone or with the medicine methotrexate and active ankylosing spondylitis.  SIMPONI is available either through the SmartJect^® autoinjector or a prefilled syringe as a subcutaneously administered injection.  For more information about SIMPONI, visit www.SIMPONI.com.  

Applications for SIMPONI as a subcutaneously administered anti-TNF-alpha therapy have been submitted in the U.S. and European Union (EU) seeking approval for the treatment of adult patients with moderately to severely active UC. 

SIMPONI is also being investigated in Phase 3 studies as a subcutaneously administered treatment for active polyarticular juvenile idiopathic arthritis (JIA).

Applications seeking approval of SIMPONI as an I.V. formulation for the treatment of adult patients with moderately to severely active RA are currently under review in the U.S. and Europe. 

Janssen Biotech, Inc. discovered and developed SIMPONI and markets the product in the United States.  Janssen pharmaceutical companies market SIMPONI in Canada, Central and South America, the Middle East, Africa and Asia Pacific. 

In Japan, Indonesia and Taiwan, Janssen Biotech, Inc. licenses distribution rights to SIMPONI to Mitsubishi Tanabe Pharma Corporation and has retained co-marketing rights in those countries.  In Europe, Russia and Turkey, Janssen Biotech, Inc. licenses distribution rights to SIMPONI to Schering-Plough (Ireland) Company, a subsidiary of Merck & Co., Inc. 

The U.S. full prescribing information for SIMPONI can be accessed at the following link:  http://www.simponi.com/sites/default/files/pdf/prescribing-information.pdf.

For further information about SIMPONI outside of the United States, please consult the relevant official product information applicable to that country location.

Important Safety Information 

SIMPONI^® (golimumab) is a prescription medicine. SIMPONI^® can lower your ability to fight infections. There are reports of serious infections caused by bacteria, fungi, or viruses that have spread throughout the body, including tuberculosis (TB) and histoplasmosis. Some of these infections have been fatal. Your doctor will test you for TB before starting SIMPONI^® and will monitor you for signs of TB during treatment. Tell your doctor if you have been in close contact with people with TB. Tell your doctor if you have been in a region (such as the Ohio and Mississippi River Valleys and the Southwest) where certain fungal infections like histoplasmosis or coccidioidomycosis are common. 

You should not start SIMPONI^® if you have any kind of infection. Tell your doctor if you are prone to or have a history of infections or have diabetes, HIV or a weak immune system. You should also tell your doctor if you are currently being treated for an infection or if you have or develop any signs of an infection such as:

• fever, sweat, or chills
• muscle aches
• cough
• shortness of breath
• blood in phlegm
• weight loss
• warm, red, or painful skin or sores on your body
• diarrhea or stomach pain
• burning when you urinate or urinate more than normal
• feel very tired

Unusual cancers have been reported in children and teenage patients taking TNF-blocker medicines. For children and adults taking TNF blockers, including SIMPONI^®, the chances for getting lymphoma or other cancers may increase. You should tell your doctor if you have had or develop lymphoma or other cancers.

Tell your doctor about all the medications you take including ORENCIA (abatacept), KINERET (anakinra), ACTEMRA (tocilizumab), RITUXAN (rituximab), or another TNF blocker, or if you are scheduled to or recently received a vaccine. People taking SIMPONI^® should not receive live vaccines.

Reactivation of hepatitis B virus has been reported in patients who are carriers of this virus and are taking TNF-blocker medicines, such as SIMPONI^®. Some of these cases have been fatal. Your doctor should do blood tests before and after you start treatment with SIMPONI^®. 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:

• feel very tired
• dark urine
• skin or eyes look yellow
• little or no appetite
• vomiting
• muscle aches
• clay-colored bowel movements
• fevers
• chills
• stomach discomfort
• skin rash

Heart failure can occur or get worse in people who use TNF blockers, including SIMPONI^®. Your doctor will closely monitor you if you have heart failure. Tell your doctor right away if you get new or worsening symptoms of heart failure like shortness of breath or swelling of your lower legs or feet. 

Rarely, people using TNF blockers, including SIMPONI^®, can have nervous system problems such as multiple sclerosis or Guillain-Barre syndrome. Tell your doctor right away if you have symptoms like vision changes, weakness in your arms or legs, or numbness or tingling in any part of your body.  

Serious liver problems can happen in people using TNF blockers, including SIMPONI^®. Contact your doctor immediately if you develop symptoms such as feeling very tired, skin or eyes look yellow, poor appetite or vomiting, or pain on the right side of your stomach.

Low blood counts have been seen with people using TNF blockers, including SIMPONI^®. If this occurs, your body may not make enough blood cells to help fight infections or help stop bleeding. Your doctor will check your blood counts before and during treatment. Tell your doctor if you have signs such as fever, bruising, bleeding easily, or paleness.

Rarely, people using TNF blockers have developed lupus-like symptoms. Tell your doctor if you have any symptoms such as a rash on your cheeks or other parts of the body, sensitivity to the sun, new joint or muscle pain, becoming very tired, chest pain or shortness of breath, swelling of the feet, ankles, and/or legs.

New or worse psoriasis symptoms may occur. Tell your doctor if you develop red scaly patches or raised bumps that are filled with pus.  

Tell your doctor if you are pregnant, planning to become pregnant or are breastfeeding or have a baby and were using SIMPONI^® during pregnancy. Tell your baby's doctor before your baby receives any vaccine because of an increased risk of infection for up to 6 months after birth.

Tell your doctor if you are allergic to rubber or latex. The needle cover contains dry natural rubber.

Tell your doctor if you have any symptoms of an allergic reaction while taking SIMPONI^® such as hives, swollen face, breathing trouble, chest pain. Some reactions can be serious and life-threatening.

Common side effects of SIMPONI^® include: upper respiratory tract infection, reaction at site of injection, and viral infections. 

Please read the Medication Guide for SIMPONI^® and discuss any questions you have with your doctor.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

About Janssen Research & Development, LLC

At Janssen Research & Development, LLC, we are united and energized by one mission—to discover and develop innovative medicines that ease patients' suffering, and solve the most important unmet medical needs of our time.  As one of the Janssen Pharmaceutical Companies of Johnson & Johnson, our strategy is to identify the biggest unmet medical needs and match them with the best science, internal or external, to find solutions for patients worldwide. We leverage our world-class discovery and development expertise, and operational excellence, to bring innovative, effective treatments in oncology, immunology, neuroscience, infectious diseases and vaccines, and cardiovascular and metabolic diseases.  For more information on Janssen R&D, visit http://www.janssenrnd.com.

References:
1. Crohn's & Colitis Foundation of America.  About Ulcerative Colitis & Proctitis.
http://www.ccfa.org/info/about/ucp.  Accessed October 19, 2012. 
2. Crohn's & Colitis Foundation of America.  Surgery for Ulcerative Colitis. http://www.ccfa.org/info/surgery/surgeryuc.
Accessed October 19, 2012.

SOURCE Janssen Research & Development, LLC

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