STELARA® (ustekinumab) Shows Positive Results In Treatment Of Systemic Lupus Erythematosus In Phase 2 Trial

SAN DIEGO, Nov. 6, 2017 /PRNewswire/ -- Janssen Research & Development, LLC (Janssen) announced today positive results from a randomized, placebo-controlled Phase 2 study investigating the anti-interleukin (IL)-12/23 monoclonal antibody STELARA^® (ustekinumab) in the treatment of active systemic lupus erythematosus (SLE or lupus). The study met the primary endpoint, with a significantly higher proportion of patients in the STELARA^® group showing improvements in lupus disease activity as measured by the SLE Responder Index (SRI)-4 response at week 24, compared with patients receiving placebo (60 percent vs. 31 percent, respectively, P=0.0046). The data are being presented as a late-breaking oral presentation at the 2017 ACR/ARHP Annual Meeting in San Diego.

"Despite the progress made in the treatment of autoimmune diseases, major unmet needs remain for patients living with lupus, a serious life-altering and, in some cases, life-threatening disease," said Ronald van Vollenhoven, M.D. Ph.D., Director of the Amsterdam Rheumatology and Immunology Center ARC and Professor of Rheumatology, University of Amsterdam and Free University; and lead study investigator. "The positive data from this Phase 2 study of ustekinumab are encouraging, highlighting the role that IL-12 and/or IL-23 may play in the pathophysiology of the disease, and offering hope for patients living with lupus and the rheumatology community."

Consistent with the primary endpoint, at week 24 patients receiving STELARA^® experienced significantly greater changes from baseline in SLE Disease Activity-2K (SLEDAI-2K) score compared with patients receiving placebo (Least Squares Mean difference -1.36, P=0.09) at a predefined alpha level of 0.1. STELARA^® did not meet statistical significance in other secondary endpoints, although investigators reported a numerical trend favoring STELARA^® for such endpoints as Physician Global Assessment, British Isles Lupus Assessment Group (BILAG)-based Combined Lupus Assessment (BICLA) and BILAG, unique measures of disease activity in SLE. A pre-specified exploratory endpoint demonstrated that the risk of a new BILAG flare (at least one new BILAG A or at least two new BILAG B) was nominally significantly lower in the STELARA^® group compared with the placebo group (HR 0.11 [95 percent CI 0.01-0.94]; nominal P=0.0078).

Similar proportions of adverse events (AEs) across STELARA^® and placebo treatment groups were reported. Serious AEs occurred in 8.3 percent of patients receiving STELARA^® and 9.5 percent receiving placebo. STELARA^® demonstrated a similar safety profile to previous trials for approved indications in moderate to severe plaque psoriasis, active psoriatic arthritis and moderately to severely active Crohn's disease. No deaths have been reported in the study to date.

"We are excited by the results from this Phase 2 study showing the potential of STELARA^® in the treatment of lupus," said Newman Yeilding, M.D., Head of Immunology Development, Janssen. "These findings, together with our knowledge of the IL-12/23 pathway and our commitment to transform the lives of patients with lupus, provide strong rationale for moving into a Phase 3 clinical development program."

The Lupus Research Alliance advocated for investigating STELARA^® in SLE given the limited treatment options and the high unmet medical need for patients.

"Lupus is a devastating autoimmune disease that affects the organs, joints and skin. Unfortunately for people living with the disease, effective treatment options to date are limited," said Kenneth Farber, President and Chief Executive Officer at Lupus Research Alliance. "In this Phase 2 study, ustekinumab showed clinical improvements in lupus disease activity and symptoms, which brings important hope to patients who have eagerly awaited new treatment options. We look forward to continuing to collaborate with Janssen on the important clinical program for ustekinumab in lupus."

Based on the results of the Phase 2 study results, Janssen plans to advance STELARA^® into a Phase 3 SLE development program in 2018.

About the Phase 2 STELARA^® SLE Trial
The efficacy and safety of ustekinumab (UST) was evaluated in a global Phase 2, randomized, placebo-controlled trial in 102 adults with seropositive SLE by Systemic Lupus International Collaborating Clinics (SLICC) criteria and active disease despite ongoing standard of care therapy (steroid, antimalarial and/or immunosuppressive therapies). Patients were randomized (3:2) to receive intravenous (IV) STELARA^® 6 mg/kg or placebo (PBO) at week 0, followed by subcutaneous (SC) injections of STELARA^® 90 mg or placebo every eight weeks, both in addition to standard of care therapy for 24 weeks. At week 24, patients in the placebo arm crossed over to active study agent. 

The primary endpoint was the proportion of patients achieving SRI-4 response at week 24. The SRI combines scores from three different validated lupus disease indexes to define responders versus non-responders, and has previously been accepted by health authorities in SLE registration trials. To achieve SRI-4 response, an individual with lupus must have at least a four-point improvement on the SLEDAI-2K score, less than 10 percent increase in PGA of disease activity and no worsening of moderate/severe organ disease on the BILAG disease activity index. Major secondary endpoints included change from baseline in SLEDAI-2K score, change from baseline in PGA of disease activity, and proportion of patients with BICLA response, all at week 24. Joint and cutaneous disease activity were also assessed with joint counts and Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI), respectively. 

Endpoint analyses included all patients who received at least one dose of study agent, had at least one measurement prior to administration, and had at least one post-baseline measurement. Patients with missing data and treatment failures were imputed as non-responders. Long-term safety and efficacy data are currently being collected through 104 weeks.

About SLE
Lupus is a chronic, inflammatory autoimmune disorder that can affect many different body systems, including joints, skin, heart, lungs, kidneys and brain.¹ SLE, the most common form of lupus, can range from mild to severe and is characterized by inflammation of any organ system including kidneys, nervous system, brain or brain vasculature, as well as potential hardening of the arteries or coronary artery disease.² The disease most often affects women and disproportionately affects women of African American, Hispanic, Asian and Native American descent compared to Caucasian women.³ Lupus is estimated to affect at least 1.5 million Americans and 5 million people worldwide.⁴

About STELARA^® (ustekinumab)
STELARA^®, a fully human interleukin (IL)-12 and IL-23 antagonist, is a prescription medicine used to treat adults and adolescents 12 years of age and older with moderate or severe plaque psoriasis who are candidates for phototherapy or systemic therapy.

STELARA^® is also indicated for the treatment of adult patients 18 years and older with active psoriatic arthritis, alone or in combination with methotrexate, and for the treatment of adult patients 18 years or older with moderately to severely active Crohn's disease. STELARA^® is in Phase 2 development for the treatment of systemic lupus erythematosus, however, safety and efficacy in the treatment of patients with SLE has not been established and STELARA^® is not approved for this indication.

The Janssen Pharmaceutical Companies of Johnson & Johnson maintain exclusive worldwide marketing rights to STELARA^®.

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 Infections
STELARA^® 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:
  
• fevers, 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. People who take STELARA^® may also be more likely to get these infections.

Cancers
STELARA^® 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 Reactions
Serious allergic reactions can occur. Stop using STELARA^® and get medical help right away if you have any symptoms such as: feeling faint, swelling of your face, eyelids, tongue, or throat, 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. Talk to your doctor about the best way to feed your baby if you take STELARA^®.

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, and tiredness in psoriasis patients; joint pain and nausea in psoriatic arthritis patients; and upper respiratory infections, redness at the injection site, vaginal yeast infections, itching, urinary tract infections, and vomiting in Crohn's disease patients. 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.

Please read the full Prescribing Information and Medication Guide for STELARA^® 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 the Janssen Pharmaceutical Companies
At 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.

Cautions Concerning Forward-Looking Statements
This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding the potential benefits and expectations for continued development of STELARA^® (ustekinumab). 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 and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; the uncertainty of commercial success; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions 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 1, 2017, including under "Item 1A. Risk Factors," it's most recently filed Quarterly Report on Form 10-Q, including in the section captioned "Cautionary Note Regarding Forward-Looking Statements," and in 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. Neither the Janssen Pharmaceutical Companies nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.

References
¹ Mayo Clinic. Lupus. Available at: http://www.mayoclinic.org/diseases-conditions/lupus/basics/definition/con-20019676. Accessed October 9, 2017.
² Lupus Foundation of America. Different Types of Lupus. Available at https://resources.lupus.org/entry/types-of-lupus. Accessed October 9, 2017.
³ Lupus Research Alliance. About Lupus. Available at http://www.lupusresearch.org/understanding-lupus/what-is-lupus/about-lupus/. Accessed October 9, 2017.
⁴ Lupus Foundation of America. What is Lupus? Available at https://resources.lupus.org/entry/what-is-lupus?utm_source=lupusorg&utm_medium=answersFAQ. Accessed October 9, 2017.

SOURCE Janssen Research & Development, LLC

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