Janssen submits applications requesting approval of STELARA® in U.S. and Europe for treatment of active Psoriatic Arthritis

Janssen Biotech, Inc. and Janssen Biologics B.V. announced today the submission of a supplemental Biologics License Application (sBLA) to the United States Food and Drug Administration (FDA) and a Type II Variation to the European Medicines Agency (EMA) requesting approval of STELARA® (ustekinumab) for the treatment of adult patients with active psoriatic arthritis. It is estimated that more than two million people in the U.S.[1]and approximately 4.2 million people across Europe[2],[3],[4] are living with psoriatic arthritis, a chronic autoimmune disease characterized by both joint inflammation and psoriasis skin lesions, for which there is no cure.

“We are pleased to present applications to health authorities in the U.S. and Europe seeking approval of STELARA for the treatment of active psoriatic arthritis, a chronic, debilitating immune-mediated inflammatory disease,” said Jerome A. Boscia, M.D., Vice President, Head of Immunology Development, Janssen Research & Development, LLC. “The efficacy and safety of STELARA, an anti–interleukin-12/23 antibody, have been evaluated in a large Phase 3 clinical development program for the treatment of active psoriatic arthritis, a disease for which tumor necrosis factor inhibitors are currently the only approved biologic therapies, and additional therapeutic options are needed.”

The applications are supported by findings from Phase 3 Multicenter, Randomised, Double-blind, Placebo-controlled trials of Ustekinumab, a Fully Human anti–IL-12/23p40 Monoclonal Antibody, Administered Subcutaneously, in Subjects with Active Psoriatic Arthritis (PSUMMIT I and PSUMMIT II), which evaluated the efficacy and safety of subcutaneously administered STELARA 45 mg or 90 mg at weeks 0, 4 and then every 12 weeks. The trials included patients diagnosed with active psoriatic arthritis who had at least five tender and five swollen joints and C-reactive protein (CRP) levels of at least 0.3 mg/dL in spite of previous treatment with conventional therapy. PSUMMIT II also included patients with previous exposure to tumor necrosis factor (TNF) inhibitors. The primary endpoints for both studies were the proportion of patients demonstrating at least a 20 percent improvement in arthritis signs and symptoms [American College of Rheumatology (ACR) 20] at week 24. Secondary endpoints at week 24 included in the submissions were: improvements in Health Assessment Questionnaire Disability Index (HAQ-DI) scores, a 50 or 70 percent improvement in arthritis signs and symptoms (ACR 50 or ACR 70), and at least a 75 percent improvement in psoriatic skin lesions as measured by the Psoriasis Area Severity Index (PASI 75) in patients with at least three percent body surface area involvement at baseline.

Data from the Janssen Research & Development–sponsored PSUMMIT I and PSUMMIT II studies were recently presented at the 2012 Annual Meeting of the American College of Rheumatology.

About Psoriatic Arthritis

Psoriatic arthritis is a chronic immune-mediated inflammatory disease characterized by both joint inflammation and the skin lesions associated with psoriasis that affects as many as 37 million people worldwide.[1] While estimates of the prevalence of psoriatic arthritis among people living with psoriasis vary, up to 30 percent may develop inflammatory arthritis. [5] Though the exact cause of psoriatic arthritis is unknown, genes, the immune system and environmental factors are all believed to play a role in the onset of the disease.[5]

About STELARA

STELARA, a human interleukin (IL)-12 and IL-23 antagonist, is currently approved in 69 countries for the treatment of moderate to severe plaque psoriasis. IL-12 and IL-23 are naturally occurring proteins that are believed to play a role in immune-mediated inflammatory diseases, including psoriasis and psoriatic arthritis.

In the U.S., STELARA is approved for the treatment of adult patients (18 years or older) with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.

In the EU, STELARA is approved for the treatment of moderate to severe plaque psoriasis in adults who failed to respond to, or who have a contraindication to, or are intolerant to other systemic therapies including ciclosporin, methotrexate and PUVA (psoralen plus UVA).[6]

STELARA is not recommended for use in children and adolescents below age 18 due to a lack of data on safety and efficacy.

In addition to the Phase 3 clinical development program in psoriatic arthritis, STELARA is in Phase 3 development for the treatment of moderately to severely active Crohn’s disease.

Janssen Biotech, Inc. discovered STELARA and has exclusive marketing rights to the product in the United States. The Janssen pharmaceutical companies maintain exclusive worldwide marketing rights to STELARA.

For more information about STELARA in the U.S., visit www.STELARAinfo.com.

For further information about STELARA outside of the U.S., please consult the relevant official product information applicable to that country location.

Important Safety Information (U.S.)

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:

• 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.

Cancer

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.

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. 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, cancer, or RPLS
• 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®. Non-live vaccinations received while taking STELARA® may not fully protect you from disease.
• are receiving or have received allergy shots, especially for serious allergic reactions
• ever had an allergic reaction to STELARA®
• receive 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 non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• other medicines that affect your immune system
• certain medicines that can affect how your liver breaks down other medicines

Common side effects of STELARA® include: upper respiratory infections, headache, and tiredness

These are not all of the side effects with STELARA®. Tell your doctor about any side effect that bothers you or does not go away. Ask your doctor or pharmacist for more information.

Please read the 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.

The U.S. full prescribing information for STELARA® can be accessed at the following link: http://www.stelarainfo.com/pdf/PrescribingInformation.pdf.

Important Safety Information (EU)[6]

Ustekinumab is a selective immunosuppressant and may have the potential to increase the risk of infections and reactivate latent infections. Serious infections have been observed in patients receiving STELARA in clinical trials. Do not start STELARA during an active infection. If a serious infection develops, monitor patients carefully and stop STELARA until the infection resolves. Patients should be evaluated for tuberculosis (TB) infection prior to initiating treatment with STELARA.

Ustekinumab is a selective immunosuppressant. Immunosuppressive agents have the potential to increase the risk of malignancy. Malignancies have been observed in patients receiving ustekinumab in clinical trials. Caution should be exercised when considering the use of STELARA in patients with a history of malignancy or when considering continuing treatment in patients who develop a malignancy.

Serious allergic reactions have been reported in the post-marketing setting, in some cases several days after treatment. Anaphylaxis and angioedema have occurred. If an anaphylactic or other serious allergic reaction occurs, administration of STELARA should be discontinued immediately and appropriate treatment instituted.

It is recommended that live viral or live bacterial vaccines (such as Bacillus of Calmette and Guérin [BCG]) should not be given concurrently with STELARA.

No overall differences in efficacy or safety in patients age 65 and older who received STELARA were observed compared to younger patients. Because there is a higher incidence of infections in the elderly population in general, caution should be used in treating the elderly.

Special Warnings and Precautions for Use[6]

Concomitant immunosuppressive therapy: Caution should be exercised when considering concomitant use of other immunosuppressants and ustekinumab or when transitioning from other immunosuppressive biologics.

References:

1. About Psoriasis: Statistics. National Psoriasis Foundation. http://www.psoriasis.org/learn_statistics. Accessed November 8, 2012.
2. Augustin M, Herberger K, Hintzen S, et al. Prevalence of skin lesions and need for treatment in a cohort of 90880 workers. Br J Dermatol. 2011;165(4):865-873.
3. Parisi R, Symmons DP, Griffiths CE, Ashcroft DM, on behalf of the Identification and Management of Psoriasis and Associated ComorbidiTy (IMPACT) project team. Global epidemiology of psoriasis: a systematic review of incidence and prevalence. J Invest Dermatol. 2012 Sep 27 [Epub ahead of print].
4. Ortonne JP, Prinz JC. Alefacept: a novel and selective biologic agent for the treatment of chronic plaque psoriasis. Eur J Dermatol. 2004;14:41-45.
5. About Psoriatic Arthritis. National Psoriasis Foundation. http://www.psoriasis.org/psoriaticarthrits. Accessed November 8, 2012.
6. Ustekinumab European Summary of Product Characteristics. March 2012.