Janssen Withdraws Application In European Union Seeking Approval Of Intravenously Administered SIMPONI®

LEIDEN, Netherlands, May 19, 2014 /PRNewswire/ -- Janssen Biologics B.V. announced today that the company has withdrawn its application seeking a change to the Marketing Authorization for SIMPONI® (golimumab) to add a new pharmaceutical form of intravenous (I.V.) administration for the treatment of adults with moderately to severely active rheumatoid arthritis (RA). Janssen Biologics informed the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) of its decision following receipt of an assessment report that indicated additional clinical data were required to further evaluate the risk:benefit profile of the I.V. formulation. 

"We have elected to withdraw our application seeking approval of SIMPONI I.V. in the European Union as we are unable at this time to provide additional clinical data beyond the pivotal Phase 3 results included in the current submission," said Newman Yeilding, M.D., Head of Immunology Development, Janssen Research & Development, LLC. "While we are disappointed that we will be unable to pursue the approval of SIMPONI I.V. as a treatment for moderately to severely active rheumatoid arthritis in the European Union, we are confident that the Phase 3 data accumulated through the SIMPONI I.V. clinical development program demonstrate a positive risk:benefit profile for this anti-tumor necrosis factor (TNF)-alpha therapy."

The withdrawal of the SIMPONI I.V. application in the European Union (EU) has no impact on SIMPONI subcutaneous or intravenous formulations in approved indications worldwide and has no consequences on ongoing clinical trials. 

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 as a once-monthly subcutaneously administered treatment in the EU for the treatment of moderately to severely active RA, active psoriatic arthritis, active ankylosing spondylitis and moderately to severely active ulcerative colitis (UC). SIMPONI is available in the EU as a subcutaneous injection either through the SmartJect® prefilled pen or a prefilled syringe.

Janssen Biotech, Inc. discovered and developed SIMPONI and has marketing rights to the product in the United States. The Janssen Pharmaceutical Companies have marketing rights to SIMPONI in Canada, Central and South America, the Middle East, Africa and Asia Pacific. 

In Europe, Russia and Turkey, Janssen Biotech, Inc. licenses distribution rights to SIMPONI to Schering-Plough (Ireland) Company, a subsidiary of Merck. 

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. 

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

Important Safety Information (EU) – Subcutaneously Administered SIMPONI 
In the European Union, SIMPONI is contraindicated in patients with active tuberculosis, severe infections such as sepsis, opportunistic infections, in patients with moderate or severe heart failure (NYHA Class III/IV), as well as in patients who are hypersensitive to SIMPONI or any of its excipients. Serious infections, including sepsis, pneumonia, tuberculosis (TB), invasive fungal and other opportunistic infections have been observed with the use of TNF antagonists including SIMPONI. Some of these infections have been fatal. SIMPONI should not be given to patients with a clinically important, active infection. Caution should be exercised when considering the use of SIMPONI in patients with a chronic infection or a history of recurrent infection. Patients must be monitored closely for infections including TB before, during and after treatment with SIMPONI. If a patient develops a new serious infection or sepsis, SIMPONI therapy should be discontinued and appropriate antimicrobial therapy should be initiated until the infection is controlled. Patients should be advised of, and avoid exposure to, potential risk factors for infection as appropriate. For patients who have resided in or traveled to regions where invasive fungal infections such as histoplasmosis, coccidioidomycosis, or blastomycosis are endemic, the benefits and risks of SIMPONI treatment should be carefully considered before initiation of SIMPONI therapy. All patients must be evaluated for the risk of TB, including latent TB, prior to initiation of SIMPONI. If active TB is diagnosed, SIMPONI must not be initiated. If latent TB is suspected or diagnosed then the benefit/risk balance of SIMPONI treatment should be considered. Treatment of latent tuberculosis infection should be initiated prior to therapy with SIMPONI. Antituberculosis therapy prior to initiating SIMPONI should also be considered in patients who have several or highly significant risk factors for tuberculosis infection and have a negative test for latent tuberculosis. Patients receiving SIMPONI should be monitored closely for signs and symptoms of active tuberculosis during and after treatment, including patients who tested negative for latent tuberculosis infections.

The use of TNF blocking agents including SIMPONI has been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic carriers of the virus. Some of these cases have been fatal. Patients should be tested for HBV infection before initiating treatment with SIMPONI. Carriers of HBV who require treatment with SIMPONI should be closely monitored during treatment with, and for several months following discontinuation of SIMPONI. In patients who develop HBV reactivation, SIMPONI should be discontinued.

Lymphomas and leukemia have been observed in patients treated with TNF blocking agents, including SIMPONI. The incidence of non-lymphoma malignancies was similar to controls, and lymphoma is seen more often than in the general population. The potential role of TNF-blocking therapy in the development of malignancies is not known. Based on an exploratory clinical trial in patients with COPD using another anti-TNF agent, caution should be exercised when using any TNF-blocking therapy in COPD patients, as well as in patients with an increased risk for malignancy due to heavy smoking. Rare post-marketing cases of hepatosplenic T-cell lymphoma (HSTCL) have been reported in patients treated with other TNF-blocking agents. This rare type of T-cell lymphoma has a very aggressive disease course and is usually fatal.

Malignancies, some fatal, have been reported among children, adolescents and young adults (up to 22 years of age) treated with TNF-blocking agents (initiation of therapy ≤ 18 years of age) in the post marketing setting. A risk for the development of malignancies in children and adolescents treated with TNF-blockers cannot be excluded.

It is not known if SIMPONI treatment influences the risk for developing dysplasia or colon cancer. All patients with ulcerative colitis who are at increased risk for dysplasia or colon carcinoma, or who had a prior history of dysplasia or colon carcinoma should be screened for dysplasia at regular intervals before therapy and throughout their disease course.

Melanoma has been reported in patients treated with TNF-blocking agents, including SIMPONI. Periodic skin examination is recommended, particularly for patients with risk factors for skin cancer.

Worsening and new onset congestive heart failure (CHF) and increased mortality due to CHF have been reported with another TNF blocker. SIMPONI has not been studied in patients with CHF. SIMPONI should be used with caution in patients with mild heart failure and must be discontinued if new or worsening symptoms of heart failure appear.

TNF-blocking agents, including SIMPONI, have been associated in rare cases with new onset or exacerbation of demyelinating disorders, including multiple sclerosis. The benefits and risks of anti-TNF treatment should be carefully considered before initiation of SIMPONI therapy in patients with pre-existing or recent onset of demyelinating disorders.

There is limited safety experience of SIMPONI treatment in patients who have undergone surgical procedures, including arthroplasty. A patient who requires surgery while on SIMPONI should be closely monitored for infections, and appropriate actions should be taken.

The possibility exists for TNF-blocking agents, including SIMPONI, to affect host defenses against infections and malignancies. Treatment with SIMPONI may result in the formation of auto-antibodies and, rarely, in the development of a lupus-like syndrome.

There have been postmarketing reports of pancytopenia, leukopenia, neutropenia, aplastic anemia, and thrombocytopenia in patients receiving TNF blockers. Cytopenias including pancytopenia, have been infrequently reported with SIMPONI in clinical trials. Discontinuation of SIMPONI should be considered in patients with significant hematologic abnormalities.

The concurrent administration of TNF-antagonists with anakinra or abatacept is not recommended. Concurrent administration has been associated with increased infections, including serious infections without increased clinical benefit. The concomitant use of SIMPONI with other biological therapeutics used to treat the same conditions as SIMPONI is not recommended because of the possibility of an increased risk of infection, and other potential pharmacological interactions.

Patients should continue to be monitored when switching from one biologic to another.

Patients treated with SIMPONI may receive concurrent vaccinations, except for live vaccines. In postmarketing experience, serious systemic hypersensitivity reactions have been reported following SIMPONI administration.

Allergic reactions may occur after first or subsequent administration of SIMPONI. If an anaphylactic reaction or other serious allergic reactions occur, administration of SIMPONI should be discontinued immediately and appropriate therapy initiated.

The needle cover on the syringe in the pre-filled pen is manufactured from dry natural rubber containing latex, and may cause allergic reactions in individuals sensitive to latex. SIMPONI also contains sorbitol; patients with rare hereditary problems of fructose intolerance should not take SIMPONI.

Patients should be given detailed instructions on how to administer SIMPONI. After proper training, patients may self inject if their physician determines that this is appropriate. The full amount of SIMPONI should be administered at all times.

Women of childbearing potential must use adequate contraception to prevent pregnancy and continue its use for at least 6 months after the last SIMPONI treatment. Women must not breast feed during and for at least 6 months after SIMPONI treatment.

The most common adverse drug reaction reported in the controlled portion from clinical trials was upper respiratory tract infection (12.6 percent of SIMPONI-treated patients compared with 10.7 percent in control-treated patients). In the controlled periods of pivotal trials, 5.1 percent of SIMPONI-treated patients had injection site reactions compared with 2.0 percent in control-treated patients. The majority of the injection site reactions were mild and moderate, and the most frequent manifestation was injection site erythema.

The SIMPONI Patient Alert Card provides safety information to the patient. It should be given and explained to all patients before treatment. Patients must show the Alert Card to any doctor involved in his/her treatment, during and up to 6 months after SIMPONI treatment.

For complete EU prescribing information, please visit www.ema.europa.eu.    

About Janssen
At Janssen, we are dedicated to addressing and solving some of the most important unmet medical needs of our time in oncology, immunology, neuroscience, infectious diseases and vaccines, and cardiovascular and metabolic diseases.  Driven by our commitment to patients, we develop innovative products, services and healthcare solutions to help people with serious diseases throughout the world.  Beyond its innovative medicines, Janssen is at the forefront of developing education and public policy initiatives to ensure patients and their families, caregivers, advocates and healthcare professionals have access to the latest treatment information, support services and quality care.

Janssen Biologics B.V., Janssen Research & Development, LLC and Janssen Biotech, Inc. are part of the Janssen Pharmaceutical Companies of Johnson & Johnson.  Please visit www.janssen.com for more information.

(This 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 Biologics B.V., Janssen Research & Development, LLC, any of the other Janssen Pharmaceutical Companies and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges inherent in new product development, including obtaining regulatory approvals and successfully marketing and selling products; competition, including technological advances, new products and patents attained by competitors; challenges to patents; changes in behavior and spending patterns or financial distress of purchasers of health care products and services; changes to governmental laws and regulations and domestic and foreign health care reforms; and general industry conditions including 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 December 29, 2013, including in Exhibit 99 thereto, and our 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.)