MSD (Merck & Co., Inc., Kenilworth, New Jersey, USA) has announced that on 22 June the European Commission approved SIMPONI® (golimumab) for the treatment of adult patients with severe, active non-radiographic axial spondyloarthritis (nr-axial SpA). This follows CHMP positive opinion issued in May 2015,1 based on the findings from the GO-AHEAD study, which demonstrated significant clinical improvement in patients with active nr-axial SpA treated with SIMPONI®, compared with patients treated with placebo, over 16 weeks.2
Nr-axial SpA and ankylosing spondylitis (AS) come under the umbrella term of Axial Spondyloarthritis (axial SpA),3 which is a painful and potentially progressive condition that mainly affects the spine and pelvic joints, commonly characterised by chronic lower back pain and stiffness.4 AS patients have evidence of radiographic damage, whereas nr-axial SpA patients do not. The burden of disease in nr-axial SpA is similar to AS.5
European Commission approval in the nr-axial SpA indication means that SIMPONI® is now - in addition to the already existing approval for ankylosing spondylitis - a treatment option for adult patients with severe, active nr-axial SpA with objective signs of inflammation (OSI), as indicated by elevated C-reactive protein (CRP) and/or magnetic resonance imaging (MRI) evidence, who have had an inadequate response to, or are intolerant to nonsteroidal anti-inflammatory drugs (NSAIDs).
"The indication of SIMPONI® in non-radiographic axial spondyloarthritis adds to a number of existing indications in rheumatology and gastroenterology," explains Dr Sean Curtis, VP, Immunology Clinical Research at MSD, "physicians now have an option to help address the treatment needs of a significant group of their patients." In rheumatology, SIMPONI® is already indicated for AS, psoriatic arthritis and rheumatoid arthritis. SIMPONI® is also approved for the treatment of ulcerative colitis.6
European Commission approval for SIMPONI® in nr-axial SpA was based on the results from the GO-AHEAD study, a Phase 3b, double-blind, randomised, placebo-controlled trial in patients with active nr-axial SpA. In the study, the primary-endpoint data showed that 71.1 per cent of patients treated with SIMPONI® achieved ASAS20 (Assessment in Spondyloarthritis International Society) at week 16 compared with 40.0 per cent of placebo-treated patients (P2 The ASAS response criteria assess symptomatic outcomes across domains including physical function, pain, global disease assessment and spinal stiffness. ASAS20 improvements were especially seen in the subpopulation of patients who had objective signs of inflammation - elevated CRP and/or MRI evidence (76.9 per cent versus 37.5 per cent, respectively; P2 Similarly, key secondary endpoints at week 16 were attained in a greater proportion of SIMPONI®-treated patients compared with placebo.
Further findings from a subanalysis of the GO-AHEAD study presented at EULAR in June showed that patients with nr-axial SpA treated with SIMPONI® had greater quality of life (QoL) improvements than those treated with placebo.7 At week 16, SIMPONI® patients had greater improvements from baseline QoL than those receiving placebo against all scales of the Ankylosing Spondylitis Quality of Life (ASQoL), EuroQoL 5-Dimension (EQ-5D), and the 36-item Short Form Health Survey (SF-36).7 Patients treated with SIMPONI® also experienced greater percentage improvements in measures of overall work impairment at week 16 versus placebo-treated patients (-21.1 vs -11.7, respectively; P=0.0391), as well as in activity impairment at week 16 (-24.9 vs -8.6, respectively; P7
"The burden of disease is similar in nr-axial SpA and AS, and effective suppression of inflammation results in a considerable improvement of pain, stiffness, function, and more general quality of life outcome parameters", explains GO-AHEAD study author Professor Joachim Sieper, Consultant and Head Rheumatologist at the Charité University Hospital, Berlin. "Such a good effect on disease activity and quality of life was nicely shown in the current study of the TNF-blocker golimumab in nr-axSpA patients compared to the group of patients treated with placebo. These results in this early phase of axial spondyloarthritis were at least as good as in the more established ankylosing spondylitis in previous trials."
Adverse events occurred in 41.0 per cent and 47.0 per cent of patients treated with SIMPONI® and placebo, respectively. There were no cases of serious infections, serious opportunistic infections, active tuberculosis, malignancies, serious systemic hypersensitivity reactions, or death during the placebo-controlled part of the study up to week 16.2
About Axial Spondyloarthritis
￼￼Axial spondyloarthritis (axial SpA) is a painful and potentially progressive form of inflammatory arthritis that mainly affects the spine and pelvic joints, and most commonly results in chronic lower back pain.4 It typically begins in the late teens and early twenties and in severe cases can result in complete fusion of the spinal vertebrae and cause structural damage to hips and other joints.4 The term axial spondyloarthritis covers both non- radiographic axial spondyloarthritis (nr-axial SpA) and ankylosing spondylitis (AS).3 In patients with nr-axial SpA, patients experience symptoms but damage to the joints does not fulfill the modified New York Criteria for AS on X-ray.8 The burden of disease in nr-axial SpA is similar to AS.5 A proportion of these nr-axial SpA patients may progress to AS with typical radiographic changes.9 Often misdiagnosed as "just back pain" in the early stages,4 axial SpA is a systemic inflammatory disease that, in addition to its effect on the spine, can affect other areas such as peripheral joints, eyes, and the bowel.4
About SIMPONI® (golimumab)
SIMPONI® is a human monoclonal antibody that targets and neutralises tumour 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. Licensed indications for SIMPONI®include: moderate to severe, active rheumatoid arthritis (RA) in adults, in combination with methotrexate, when the response to disease-modifying anti-rheumatic drug (DMARD) therapy including methotrexate has been inadequate; severe, active and progressive RA, in combination with methotrexate, in adults not previously treated with methotrexate; active and progressive psoriatic arthritis in adult patients, alone or in combination with methotrexate, when the response to previous DMARD therapy has been inadequate; and severe, active AS in adults who have responded inadequately to conventional therapy. SIMPONI® is now also indicated for the treatment of adults with severe active nr-axial SpA with OSI as indicated by elevated CRP and/or MRI evidence of active bony inflammation, who have had an inadequate response to, or are intolerant to non- steroidal anti-inflammatory drugs.
SIMPONI® is also the first and only subcutaneous anti-tumor necrosis factor (TNF)-alpha treatment administered as an every-four-week maintenance therapy for the treatment of adult patients with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy, including corticosteroids and 6- mercaptopurine or azathioprine, or who are intolerant to or have medical contraindications for such therapies. SIMPONI® is available either through the SmartJect® autoinjector/prefilled pen or a prefilled syringe as a SC administered injection.6
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 Japan, Indonesia, and Taiwan, Janssen Biotech, Inc. licenses distribution rights to SIMPONI® to Mitsubishi Tanabe Pharma Corporation. In Europe, Russia and Turkey, Janssen Biotech, Inc. licenses distribution rights for SIMPONI® to Schering-Plough (Ireland) Company, a subsidiary of Merck & Co., Inc., Kenilworth, New Jersey, USA.
Please refer to the Summary of Product Characteristics for full information on 'SIMPONI®' including contraindications, precautions, special warnings and side effects. Available from: http://www.medicines.org.uk/EMC/medicine/23766/SPC/Simponi+50+mg+solution+for+injection/
GO-AHEAD was a Phase 3b double-blind, randomised, placebo-controlled trial conducted in patients 18 to 45 years of age with active non-radiographic axial spondyloarthritis (nr-axial SpA), diagnosed according to the Assessment of the SpondyloArthritis international Society (ASAS) criteria.2
The study evaluated 197 patients who were treated with either SIMPONI® (golimumab) 50 mg (n=97) or placebo (n=100) subcutaneous injections every four weeks. The mean patient age was 31 years and more than half of the patients were male (57 per cent). The primary endpoint of the study was the percentage of patients who attained ASAS20 at week 16. Key secondary endpoints included percentage of patients attaining ASAS40, ASAS partial remission, Bath AS Disease Activity Index (BASDAI) 50; and change from baseline in sacroiliac joint inflammation on magnetic resonance imaging (MRI) (SPondyloArthritis Research Consortium of Canada [SPARCC] score).2
The study also assessed a subgroup of patients who showed objective signs of inflammation (OSI) by MRI and/or elevated C-reactive protein (CRP) at baseline. This subset of patients comprised approximately 80 per cent of the total population.2
Adverse events occurred in 41 per cent and 47 per cent of patients treated with SIMPONI® and placebo, respectively. Serious adverse events occurred in one SIMPONI® patient (female partner of patient-reported fetal death) and two placebo patients (presence of gallstones and back pain). There were no events of serious infections, serious opportunistic infections, active tuberculosis, malignancies, serious systemic hypersensitivity, or deaths during the placebo-controlled part of the study up to week 16.2