New Phase 3 Study Findings Show STELARA® Maintained Clinical Remission After One Year Of Treatment In Patients With Moderate To Severe Crohn's Disease

SAN DIEGO, May 23, 2016 /PRNewswire/ -- Janssen Research & Development, LLC (Janssen) Phase 3 data presented for the first time at Digestive Disease Week® 2016 showed that a significantly greater proportion of adult patients with moderate to severe Crohn's disease receiving STELARA® (ustekinumab) subcutaneous (SC) maintenance therapy were in clinical remission at one year.  The Phase 3 IM-UNITI maintenance study, which evaluated 388 patients who achieved clinical response eight weeks after a single intravenous infusion of STELARA® in the UNITI-1 and UNITI-2 Phase 3 induction studies, showed that 53 percent of patients receiving a STELARA® 90 mg SC injection every eight weeks (Q8W) and 49 percent of patients receiving a STELARA® 90 mg SC injection every 12 weeks (Q12W) were in clinical remission at week 44, the study's primary endpoint, compared with 36 percent of patients receiving placebo (P = 0.005 and P = 0.040, respectively).  Clinical remission was defined by a Crohn's Disease Activity Index (CDAI) score of less than 150 points; CDAI is a symptom-based disease assessment tool commonly used in clinical trials to quantify Crohn's disease activity. 

Applications seeking approval of STELARA® for the treatment of moderately to severely active Crohn's disease are currently under review in the United States and Europe.  STELARA®, approved for the treatment of moderate to severe plaque psoriasis and active psoriatic arthritis in many countries, is a novel biologic therapy that targets interleukin (IL)-12 and IL-23 cytokines, which are believed to play a role in immune-mediated diseases, including Crohn's disease. 

"The totality of the induction and maintenance data over the course of one year show the potential of this biologic therapy in inducing and maintaining a clinically relevant therapeutic effect in patients with moderate to severe Crohn's disease," said William Sandborn, M.D., Chief, Division of Gastroenterology, and Professor of Medicine, University of California, San Diego, and study investigator.  "The results of this comprehensive Phase 3 program-which included anti-tumor necrosis factor (TNF)-alpha naïve, exposed and failure patients-demonstrate the potential of STELARA® to provide significant benefit for patients in need of an effective therapy."

The IM-UNITI maintenance study represents the third pivotal study in the year-long, comprehensive Phase 3 clinical development program investigating STELARA® for the treatment of moderate to severe Crohn's disease.  The findings, presented as part of the Distinguished Abstract Plenary at Digestive Disease Week 2016, follow Phase 3 results from the UNITI-1 induction study, which demonstrated the efficacy and safety of STELARA® in patients who had previously failed or were intolerant to treatment with one or more anti-TNF-alpha therapies, and the Phase 3 UNITI-2 induction study, which demonstrated the efficacy and safety of STELARA® in patients who had previously failed conventional therapy, the majority of whom were naïve to treatment with anti-TNF-alpha therapy.  Patients responding to a single intravenous dose of STELARA® in the induction studies were re-randomized in the IM-UNITI maintenance study to receive STELARA® 90 mg SC Q8W, STELARA® 90 mg SC Q12W or placebo (withdrawal from therapy) and were followed for a combined one year of treatment.  All patients randomized in the IM-UNITI maintenance study had achieved clinical response to STELARA® at week 8, and approximately 60 percent of patients were in clinical remission at entry into the IM-UNITI study. 

Major secondary endpoints of the IM-UNITI study included clinical response, clinical remission among patients in remission after induction, corticosteroid-free remission, and clinical remission in patients refractory or intolerant to anti-TNF-alpha therapies (UNITI-1 subpopulation), all at week 44.

• Clinical response (an improvement in a CDAI score of at least 100 points after STELARA® induction) was maintained in a significantly greater proportion of patients receiving STELARA® 90 mg SC Q8W (59 percent) and STELARA® 90 mg SC Q12W (58 percent) compared with patients receiving placebo (44 percent) [P = 0.018 and P = 0.033, respectively].
• Of those patients who were in clinical remission at the start of the IM-UNITI study, 67 percent receiving STELARA® 90 mg SC Q8W and 56 percent of patients receiving STELARA® 90 mg SC Q12W were in clinical remission at week 44 compared with 46 percent of patients receiving placebo (P P = not significant, respectively).
• A significantly higher percentage of patients receiving STELARA® 90 mg SC Q8W (47 percent) and a higher percentage of patients receiving STELARA® 90 mg SC Q12W (43 percent) who were not receiving concomitant corticosteroids were in clinical remission at week 44 compared with 30 percent of patients receiving placebo (P = 0.004; nominal P = 0.035, respectively).
• Numerically higher proportions within the subgroup of patients who had previously failed or were intolerant to treatment with one or more anti-TNF-alpha therapies (UNITI-1 subpopulation) achieved clinical remission while receiving STELARA® maintenance therapy at week 44, with similar treatment effects to the overall population, (41 percent for STELARA® 90 mg SC Q8W and 39 percent for STELARA® 90 mg SC Q12W) compared with 26 percent of patients receiving placebo (P = not significant for both).

Through week 44 (placebo-controlled period), adverse events (AEs) were reported in similar proportions across STELARA® and placebo treatment groups.  Serious AEs occurred in 10 percent, 12 percent and 15 percent of patients receiving a STELARA® 90 mg SC Q8W, STELARA® 90 mg SC Q12W and placebo, respectively; 2 percent, 5 percent and 2 percent of patients reported serious infections in these respective groups.  In the placebo controlled period, no deaths or major adverse cardiovascular events (MACE) were reported, and two patients reported malignancies (one case of basal cell carcinoma in each of the placebo and STELARA® 90 mg SC Q8W groups). 

"These maintenance data complement the induction data previously presented and provide important insights into the efficacy and safety profile of STELARA® for the treatment of moderately to severely active Crohn's disease," said Newman Yeilding, M.D., Head of Immunology Development, Janssen Research & Development, LLC.  "Pending approval, we look forward to bringing STELARA® to patients who may benefit from this new therapeutic option and providing gastroenterologists with a new alternative to treat Crohn's disease."

Additional data from the STELARA® Phase 3 Crohn's disease clinical development program being presented at Digestive Disease Week® 2016 include:

• Assessment of Serum C-Reactive Protein, Fecal Lactoferrin, and Fecal Calprotectin in Patients With Moderate-Severely Active Crohn's Disease: Results From the IM-UNITI Maintenance Study
• Evidence of Content Validity and Psychometric Properties of SF-36 for Measuring Health-Related Quality of Life of Patients With Crohn's Disease
• Molecular Response to Ustekinumab in Moderate-to-severe Crohn's Disease by Serum Protein Analysis: Results from UNITI-1 Induction, UNITI-2 Induction, and IM-UNITI Maintenance Studies
• Pharmacokinetics and Exposure-Response Relationships of Ustekinumab during IV Induction and SC Maintenance Treatment of Patients with Crohn's Disease with Ustekinumab: Results from the UNITI-1, UNITI-2, and IM-UNITI Studies
• Ustekinumab Improves General Health Status and Disease-Specific Health Related Quality of Life of Patients with Moderate to Severe Crohn's Disease: Results from the UNITI and IM-UNITI Phase 3 Clinical Trials

About the IM-UNITI Trial IM-UNITI, a Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel group study, evaluated the efficacy and safety of STELARA® maintenance therapy in adult patients with moderate to severe Crohn's disease.  Patients (n=388) who had responded to a single intravenous dose of STELARA® in the UNITI-1 or UNITI-2 induction studies were randomized equally to receive maintenance SC injections of STELARA® 90 mg SC Q8W or Q12W, or placebo).  Together, the UNITI-1 and UNITI-2 induction studies and the IM-UNITI maintenance study represent one year of therapy.  The primary endpoint was clinical remission at week 44, defined by CDAI scores less than 150 points.  Major secondary endpoints at week 44 included clinical response, measured by the proportion of patients who achieved at least a 100-point reduction from baseline CDAI scores, corticosteroid-free clinical remission, clinical remission among patients in remission at the start of the IM-UNITI study, and clinical remission in the subgroup of patients refractory or intolerant to treatment with one or more anti-TNF-alpha therapies.

About Crohn's DiseaseMore than five million people worldwide are living with Crohn's disease and ulcerative colitis-collectively known as inflammatory bowel disease (IBD).1  Crohn's disease is a chronic inflammatory condition of the gastrointestinal tract that affects approximately 700,000 Americans.  The cause of Crohn's disease is not known, but the disease is associated with abnormalities of the immune system that could be triggered by a genetic predisposition or diet and other environmental factors.  Symptoms of Crohn's disease can vary but often include abdominal pain and tenderness, frequent diarrhea, rectal bleeding, weight loss and fever.  There is currently no cure for Crohn's disease.2

About STELARA® (ustekinumab)STELARA®, a human IL-12 and IL-23 antagonist, is approved in the United States for the treatment of adult patients (18 years or older) with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.  STELARA® is also approved for the treatment of adult patients (18 years or older) with active psoriatic arthritis and can be used alone or in combination with methotrexate (MTX).

The Janssen Pharmaceutical Companies of Johnson & Johnson maintain exclusive worldwide marketing rights to STELARA®, which is currently approved for the treatment of moderate to severe plaque psoriasis in 87 countries and psoriatic arthritis in 71 countries.

Important Safety Information STELARA® is a prescription medicine that affects your immune system. STELARA® can increase your chance of having serious side effects including:

Serious InfectionsSTELARA® may lower your ability to fight infections and may increase your risk of infections. While taking STELARA®, some people have serious infections, which may require hospitalization, including tuberculosis (TB), and infections caused by bacteria, fungi, or viruses.

• Your doctor should check you for TB before starting STELARA® and watch you closely for signs and symptoms of TB during treatment with STELARA®.
• If your doctor feels that you are at risk for TB, you may be treated for TB before and during treatment with STELARA®.

You should not start taking STELARA® if you have any kind of infection unless your doctor says it is okay.

Before starting STELARA®, tell your doctor if you think you have an infection or have symptoms of an infection such as:

• fever, sweats, or chills
• muscle aches
• cough
• shortness of breath
• blood in your phlegm
• weight loss
• warm, red, or painful skin or sores on your body
• diarrhea or stomach pain
• burning when you urinate or urinate more often than normal
• feel very tired
• are being treated for an infection
• get a lot of infections or have infections that keep coming back
• have TB, or have been in close contact with someone who has TB

After starting STELARA®, call your doctor right away if you have any symptoms of an infection (see above).

STELARA® can make you more likely to get infections or make an infection that you have worse. People who have a genetic problem where the body does not make any of the proteins interleukin 12 (IL-12) and interleukin 23 (IL-23) are at a higher risk for certain serious infections that can spread throughout the body and cause death. It is not known if people who take STELARA® will get any of these infections because of the effects of STELARA® on these proteins.

CancersSTELARA® may decrease the activity of your immune system and increase your risk for certain types of cancer. Tell your doctor if you have ever had any type of cancer. Some people who had risk factors for skin cancer developed certain types of skin cancers while receiving STELARA®. Tell your doctor if you have any new skin growths.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS)RPLS is a rare condition that affects the brain and can cause death. The cause of RPLS is not known. If RPLS is found early and treated, most people recover. Tell your doctor right away if you have any new or worsening medical problems including: headache, seizures, confusion, and vision problems.

Serious Allergic ReactionsSerious allergic reactions can occur. Get medical help right away if you have any symptoms such as: feeling faint, swelling of your face, eyelids, tongue, or throat, trouble breathing, throat or chest tightness, or skin rash.

Before receiving STELARA®, tell your doctor if you:

• have any of the conditions or symptoms listed above for serious infections, cancers, or RPLS.
• ever had an allergic reaction to STELARA® or any of its ingredients. Ask your doctor if you are not sure.
• are allergic to latex. The needle cover on the prefilled syringe contains latex.
• have recently received or are scheduled to receive an immunization (vaccine). People who take STELARA® should not receive live vaccines. Tell your doctor if anyone in your house needs a vaccine. The viruses used in some types of vaccines can spread to people with a weakened immune system, and can cause serious problems. You should not receive the BCG vaccine during the one year before taking STELARA® or one year after you stop taking STELARA®.
• have any new or changing lesions within psoriasis areas or on normal skin.
• are receiving or have received allergy shots, especially for serious allergic reactions.
• receive or have received phototherapy for your psoriasis.
• have any other medical conditions.
• are pregnant or plan to become pregnant. It is not known if STELARA® will harm your unborn baby. You and your doctor should decide if you will take STELARA®.
• are breast-feeding or plan to breast-feed. It is thought that STELARA® passes into your breast milk. You should not breast-feed while taking STELARA® without first talking to your doctor.

Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.

When prescribed STELARA®:

• Use STELARA® exactly as prescribed by your doctor
• If your doctor decides that you or a caregiver may give your injections of STELARA® at home, you should receive training on the right way to prepare and inject STELARA®. Do not try to inject STELARA® yourself until you or your caregiver has been shown how to inject STELARA® by your doctor or nurse.

Common side effects of STELARA® include: upper respiratory infections, headache, tiredness, joint pain and nausea. These are not all of the possible side effects with STELARA®. Tell your doctor about any side effect that you experience. Ask your doctor or pharmacist for more information.

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.

Please read the Full Prescribing Information, including the Medication Guide for STELARA®, and discuss any questions you have with your doctor.

About the Janssen Pharmaceutical CompaniesAt the Janssen Pharmaceutical Companies of Johnson & Johnson, we are working to create a world without disease.  Transforming lives by finding new and better ways to prevent, intercept, treat and cure disease inspires us.  We bring together the best minds and pursue the most promising science.  We are Janssen.  We collaborate with the world for the health of everyone in it.  Learn more at www.janssen.com.  Follow us on Twitter at https://twitter.com/JanssenGlobal.

About Digestive Disease Week®Digestive Disease Week® (DDW) is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery.  Jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE) and the Society for Surgery of the Alimentary Tract (SSAT), DDW takes place May 21-24, 2016, at the San Diego Convention Center, San Diego, CA.  The meeting showcases more than 5,000 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology.  More information can be found at www.ddw.org.

Cautions Concerning Forward-Looking StatementsThis press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding product development. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges inherent in product research and development, including uncertainty of clinical success and obtaining regulatory approvals; uncertainty of commercial success for products; competition, including technological advances, new products and patents attained by competitors; challenges to patents; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and description of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended January 3, 2016, including in Exhibit 99 thereto, and the company's subsequent filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. None of the Janssen Pharmaceutical Companies or Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.

References

1. World IBD Day. Home. Available at http://www.worldibdday.org/index.html. Accessed May 10, 2016.
2. Crohn's & Colitis Foundation of America. What is Crohn's Disease?. Available at http://www.ccfa.org/what-are-crohns-and-colitis/what-is-crohns-disease/. Accessed May 10, 2016.

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