Janssen Submits Application Seeking Approval of SIMPONI® in European Union for Non-Radiographic Axial Spondyloarthritis

LEIDEN, Netherlands, Nov. 18, 2014 /PRNewswire/ -- Janssen Biologics B.V. (Janssen) announced today that a Type II Variation has been filed with the European Medicines Agency seeking approval of SIMPONI^® (golimumab) for the treatment of severe active non-radiographic axial spondyloarthritis (nr-AxSpA).  Nr-AxSpA is a form of spondyloarthritis—chronic inflammatory diseases affecting the spine—in which the predominant symptom is back pain and stiffness.  While patients with nr-AxSpA may not initially present with evidence of structural damage to the joints, many will progress to having some degree of spinal fusion (e.g., ankylosing spondylitis), particularly young males.¹

"We believe that this new application for SIMPONI in the European Union shows the potential role this anti-TNF-alpha therapy may play as a treatment option for people living with this debilitating inflammatory disease," said Newman Yeilding, M.D., Vice President, Head of Immunology Development, Janssen Research & Development, LLC.  "We look forward to collaborating with the European Medicines Agency to progress SIMPONI as a treatment for people living with non-radiographic axial spondyloarthritis."

The application is supported by data from the Phase 3 GO-AHEAD trial, a MSD- (known as Merck in the United States and Canada) sponsored program conducted in collaboration with Janssen, which evaluated the efficacy and safety of SIMPONI compared with placebo in adults with active nr-AxSpA.  Data from the GO-AHEAD study will be presented at the 2014 American College of Rheumatology Annual Meeting.

About GO-AHEAD
GO-AHEAD, a multicenter, randomized, double-blind, placebo-controlled Phase 3 study, evaluated the efficacy and safety of SIMPONI in adults with active nr-AxSpA.  Patients (N=197) had been diagnosed no more than five years prior with chronic back pain of at least three months' duration.  In addition, patients were inadequately controlled with 30 days of optimal daily doses of at least one non-steroidal anti-inflammatory drug (NSAID) or were intolerant to such therapy.

The study had two parts.  In part 1 of the study, patients were randomized equally to receive SIMPONI 50 mg or placebo at weeks 0, 4, 8 and 12.  Beginning at week 16—part 2 of the study—all patients began receiving open-label SIMPONI 50 mg every four weeks.  Part 2 was 44 weeks in duration, with 36 weeks of treatment and an eight-week safety follow-up period.  The primary endpoint of the study was an Assessment in Ankylosing Spondylitis (ASAS) 20 response at week 16.  Key secondary endpoints at week 16 included ASAS 40 response, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 response, ASAS partial remission, and change from baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Magnetic Resonance Imaging (MRI) Sacroiliac Joints Scoring. 

About Spondyloarthritis  
Spondyloarthritis refers to a family of chronic, inflammatory diseases that share common clinical features, including inflammation of the joints and the entheses (sites where ligaments and tendons attach to bones).  AxSpA is a type of spondyloarthritis that mainly affects the spine and pelvic joints.  The primary symptoms of AxSpA include pain and stiffness of the spine, and the disease can eventually progress to include bone destruction, which can lead to spinal deformity and dysfunction.  Unlike ankylosing spondylitis, which is another type of AxSpA, patients with nr-AxSpA may not present with traditional X-ray evidence of structural damage.¹  It is estimated that 0.3 to 2.5 percent of the European population are living with some type of spondyloarthritis, with men affected more frequently than women.²   

About SIMPONI^® (golimumab)
SIMPONI is a human monoclonal antibody that targets and neutralises excess tumor necrosis factor (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 85 countries for rheumatologic indications, including the European Union (EU), where SIMPONI received European Commission approval in October 2009 for the treatment of moderate-to-severe, active rheumatoid arthritis in combination with methotrexate, for the treatment of active and progressive psoriatic arthritis alone or in combination with methotrexate and for the treatment of severe, active ankylosing spondylitis.  In September 2013, SIMPONI received European Commission approval for the treatment of moderately to severely active ulcerative colitis.  SIMPONI is available either through the SmartJect^® autoinjector/prefilled pen or a prefilled syringe as a subcutaneously administered injection.  

Janssen Biotech, Inc. discovered and developed SIMPONI and markets the product in the United States.  The Janssen Pharmaceutical Companies market 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 & Co., Inc. 

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. 

Important Safety Information
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, 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 should be monitored for signs and symptoms of infection before, during and for several months after treatment with SIMPONI.  If a patient develops a new serious infection or sepsis, SIMPONI therapy should be discontinued and appropriate antimicrobial or antifungal 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.   Patients must be evaluated for the risk of tuberculosis (TB), including latent tuberculosis, 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 significant risk factors for tuberculosis infection and have a negative test for latent tuberculosis, or for patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed.  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 in patients who are chronic carriers of the virus.  Some of these cases have been fatal.  Chronic carriers of hepatitis B should be appropriately evaluated and monitored prior to the initiation of, during treatment with, and for several months following discontinuation of SIMPONI.  In patients who develop HBV reactivation, SIMPONI should be discontinued.

Lymphomas 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, 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.

Patients treated with SIMPONI may receive concurrent vaccinations, except for live vaccines.  Non-serious allergic reactions associated with SIMPONI occurred in clinical trials, and included urticaria, bronchospasm, and hypersensitivity. In post-marketing experience, serious systemic hypersensitivity reactions (including anaphylactic reaction) have been reported following SIMPONI administration. Some of these reactions occurred after the first 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.  All patients should be monitored for anaphylactic or other serious allergic reactions.

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. Mild injection site reactions commonly occur. In case of severe reaction(s) SIMPONI should be discontinued.

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

The most common adverse reaction reported from the controlled period of pivotal 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 period 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 six months after SIMPONI treatment.

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

About Janssen Biologics B.V., Janssen Research & Development, LLC and Janssen Biotech, Inc.
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, Janssen Biotech, Inc. and/or Johnson & Johnson.  Risks and uncertainties include, but are not limited to: challenges inherent in new product development, including obtaining regulatory approvals; competition, including technological advances, new products and patents attained by competitors; challenges to patents; changes to 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 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 nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.)

References

¹ Spondyloarthritis. The American College of Rheumatology website. https://www.rheumatology.org/Practice/Clinical/Patients/Diseases_And_Conditions/Spondylarthritis_%28Spondylarthropathy%29/. Accessed October 23, 2014.
² Stolwijk C, Boonen A, van Tubergen A, Reveille JD. Epidemiology of Spondyloarthritis. Rheum Dis Clin N Am. 2012;38(3):441-76. doi: 10.1016/j.rdc.2012.09.003.

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